Block 1

BZYET-141
IMMUNOLOGY
Indira Gandhi
National Open University
School of Sciences
VOL
1
IMMUNOLOGY-I
BLOCK 1
INTRODUCTION TO IMMUNOLOGY 7
BLOCK 2
ANTIGEN-ANTIBODY 109
IMMUNOLOGY
Immunology is the study of the immune system and is a very important branch of the medical
and biological sciences. The immune system protects us from infection through various lines
of defence. If the immune system is not functioning as it should, it can result in diseases such
as autoimmunity, allergy and cancer.
Immunology is the branch of biomedical science that deals with the response of an organism
to antigenic challenge and its recognition of what is self and what is not. It deals with the
defence mechanisms including all physical, chemical and biological properties of the
organism that help it to combat its susceptibility to foreign organism.
The immune system is divided into those which are static or innate to the organism and
those which are responsive, adaptive to a potential pathogen.
The innate system is older system in evolutionary terms, that forms the first line of defence. It
is non- specific and the resistance is static. (It does not improve with repeated exposure and
there is no memory on subsequent exposure). This includes physical defences such as skin
and epithelial surfaces, cilia, acidic gastric content, fever etc. Others are biochemical
defences such as acute phase reactants and complement, interferon. Cellular components
include natural killer cells, RES phagocytes.
The adaptive system is the second line of defence and is activated once the innate system
has been overwhelmed. It is specific to the infective agent and can store the information
about the invader as the memory to show an enhanced response to subsequent challenge.
The word immunity was derived from the Latin word ‘immunis’ meaning exempt.
Immunology deals with physical, chemical and physiological characteristics of the

components of the immune system in vitro, in situ and in vivo. Immunology has a vast array
of uses in several disciplines of science and medical science.
The key primary lymphoid organs of the immune system are thymus and bone marrow and
secondary lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids
and skin. The actual components of the immune system are cellular in nature and not
associated with any specific organ. They are widely present in circulation throughout the
body.
Immunology course is discipline specific elective of fifth semester. It has two volumes i.e.
Immunology I and Immunology II. Volume 1 has two blocks i.e. Block I and Block 2 and
Volume 2 has two blocks i.e. Block 3 and Block 4. Volume 1 has 8 units and Volume 2 has 7
units.
Block 1 comprises five units. It traces the historical perspective of immunology. Basic
concepts of immunology viz. self and non self, Clonal selection theory and major categories
of human pathogens and host pathogen interaction are discussed in the introductory unit.
Components, cells and organs of immune system are elaborated in first block. Innate
immunity is the inborn immunity that serves as the first line of defence by creating barriers
against any pathogens through anatomical, humoral and cellular barriers. Adaptive immunity
is specific to antigens and effective in combat against invading microbes. The major
population of lymphocytes involved in adaptive immune responses are B and T-lymphocytes.
B-cell immune response is also known as humoral immunity and T cell immunity is also
known as cellular immunity. 3
Immune system of human is a network of organs and tissues connected by blood vessels
and lymphatic system. The organs of lymphatic system are primary and secondary
lymphoid organs. Bone marrow and thymus, are primary lymphoid organs. Spleen, tonsils,
and lymph nodes are secondary lymphoid organs. All the blood cells including cells of
immune system are derived from pHSC stem cells in the bone marrow. The
microenvironment in which these cells are found influences their development and on
maturation pHSC cells give rise to myeloid and lymphoid progenitors. From myeloid
progenitor, four types of cell arise i.e. megakaryocytes, erythroblast, myeloblast and
monoblast. The cell types that are principal to immune system are called as lymphocytes that
arise from lymphoid pregenitor cells.
Block 2 discusses about antigens, antibodies, and their interaction. Antigen are substances
that can bind with antibodies or cell receptors which may (immunogen) or may not elicit an
immune response (haptens). So all immunogens are antigens but not all antigens are
immunogens. Only a small portion of antigen, called as epitope, binds to B and T cells. The
mechanism of binding to T and B cells are different. Antigens can be classified as
exogenous, endogenous, autoantigens and alloantigens based on origin. Antibodies are a
heterogenous group of globulin proteins found in serum collectively called as
immunoglobulins (IgG, IgH, IgA, IgE, IgD) that mediate phagocytosis, triggering of
inflammation and other important immunological responses. Antibodies can be specific to
several epitopes of antigens (polyclonal antibodies) or be specific to only one epitope of the
antigen which are called as monoclonal antibodies.
Volume II, Immunology II comprises Blocks 3 and 4 which have seven units in all. It speaks
about working of the immune system and role of immune system in fighting diseases. It
introduces to structure and function of MHC. Different pathways of antigen presentation
(exogenous and endogenous) and processing are also discussed.
T cell activation requires 3 components i.e. T cell complex – MHC: peptide interaction. T
helper cells carry co-receptor CD4+that recognise class II MHC molecule and T cytotoxic cells
bear CD8+ co-receptor and recognise class I MHC molecules. Activated helper T cells can
differentiate into various subsets which perform different functions.
Cytokines are diverse groups of non antibody glycoproteins usually smaller than 30kDa that
form a part of intercellular signalling molecules secreted by specific cells of immune system.
Lymphokines, monokines and interleukins are various types of cytokines. Complement
system is an integral part of innate immune system that are formed by number of proteins
>20 which are synthesised in liver and circulated in blood and tissue fluids. Complement
system induces opsonisation, chemotaxis, inflammation and lysis pathogens.
Pathogens produce diseases in humans by the colonisation of host tissues or by liberating

toxins. To protect humans against diseases from microbes, immunisation is used as a means
of providing specific protection against pathogens by stimulation of one’s immune system.
Such specific immunity can be attained either by active or passive immunisation through
vaccine.
Objectives
After studying this course you should be able to:
• trace the course of development of the field of immunology,
4 • explain an overview of the immune system,

• define innate immunity,
• list the various innate immunity barriers,
• discuss the functions of NK cells,
• define complement system and list its functions,
• explain various complement activation pathways,
• gain an insight about the adaptive immune system,
• differentiate between naturally and artificially acquired immunity,
• explain B and T lymphocytes,
• differentiate between humoral and cell-mediated immunity,
• compare and differentiate functions executed by primary and secondary lymphoid

organs,
• enlist the biological significance exhibited by lymphoid organs,
• discuss the properties of antigen recognized by the B and T cells,
• list the structure and properties of antigens,
• differentiate between T and B epitopes,
• define adjuvants and discuss their functions,
• explain the immunological variants of antibodies present in mammalian body,
• distinguish between isotype, idiotype and allotype antibodies,
• differentiate between polyclonal and monoclonal antibodies, and
• discuss the principles and applications of important immunological tools, and

techniques.
5
BZYET-141
IMMUNOLOGY
Indira Gandhi
National Open University
School of Sciences
Block
1
INTRODUCTION TO IMMUNOLOGY
UNIT 1
Overview of the Immune System 11
UNIT 2
Components of Immune System-I 31
UNIT 3
Components of Immune System-II 54
UNIT 4
Organs of Immune System 76
UNIT 5
Cells of the Immune System 87
Course Design Committee
Prof. M.S. Nathawat Prof. Neera Kapoor
Former Director School of Sciences, IGNOU
School of Sciences, IGNOU Maidan Garhi, New Delhi-110068
Maidan Garhi, New Delhi-110068 Dr. Bano Saidullah (Retd.)
Prof. Pratima Ray School of Sciences, IGNOU
Department of Biotechnology Maidan Garhi, New Delhi-110068
Jamia Hamdard University, Delhi-110062 Dr. Abdul Kareem
Prof. Sarita Sachdeva School of Sciences, IGNOU, Maidan Garhi
Department of Biotechnology New Delhi-110068
Manav Rachna International Institute of Dr. Arvind Kr. Shakya
Research and Studies, Faridabad
Haryana-121004 School of Sciences, IGNOU, Maidan Garhi
New Delhi-110068
Dr. Indrakant K. Singh
Molecular Biology Research Laboratory Dr. Swati Omanwar
Department of Zoology, Deshbandhu College Former, Consultant, School of Sciences, IGNOU
University of Delhi, Delhi-110019 Maidan Garhi, New Delhi-110068
Dr. Moses Rinchui N.
Department of Zoology, Deshbandhu College
University of Delhi, Kalkaji, New Delhi-110019
Block Preparation Team

Dr. Shivani G. Varmani Dr. Poonam Sharma
Department of Biomedical Science Gargi College, University of Delhi
Bhaskaracharya College of Applied Sciences New Delhi-110049 (Unit 5)
University of Delhi, Delhi-110075
(Units 1, 2 and 3) School of Sciences
Dr. Abdul Kareem Prof. Neera Kapoor (Units 1 to 5)
School of Sciences, IGNOU, Maidan Garhi
New Delhi-110068 (Unit 4)
Course Coordinator : Prof. Neera Kapoor
Course Editor : Dr. Indrakant K. Singh
University of Delhi, Delhi-110019
Associate Editor : Dr. Moses Rinchui N.
University of Delhi, Kalkaji, New Delhi-110019
Production
Mr. Hemant Kumar, SO (P), MPDD, IGNOU
Acknowledgement:
• Prof. Neera Kapoor and Mr. Ajit Kumar, Suggestions for figures and Cover Design.
• Mr. Vikas Kumar, JAT and Mr. Ajit Kumar for word processing and CRC preparation.
August, 2021
Indira Gandhi National Open University, 2021
ISBN : 978-93-89969-15-3
All rights reserved. No part of this work may be reproduced in any form, by mimeograph or any other
means, without permission in writing from Indira Gandhi National Open University.
Further information on Indira Gandhi National Open University courses may be obtained from the
University’s office at Maidan Garhi, New Delhi-110 068 or IGNOU website www.ignou.ac.in.
Printed and published on behalf of Indira Gandhi National Open University, New Delhi by the
Registrar, MPDD, IGNOU.
Printed at:
BLOCK 1: INTRODUCTION TO IMMUNOLOGY
The immune system is present everywhere in the body. The specialized cells and molecules
which comprise the immune system cannot function in isolation. There must be a constant
crosstalk and interaction among cells and tissues throughout the body. Immune cells must be
able to exchange information or messages with the cells of other major regulatory systems
i.e: the brain, the nervous system and endocrine system etc. The most significant response
takes place within the tissue. In the past few years immunologists have been able to
understand the cellular and molecular features which actually indeed encourage the immune
cells to leave the circulation and enter the tissue. In response to a variety of stimuli, the blood
and the lymphatic vessels are considered to be the key regulators of immune and
inflammatory responses. They provide a dynamic interface between the tissues and the
circulating fluids, cells and molecules under certain circumstances.
The immune system is defence system that protects animals against attack by pathogens
and cancer. The immune system has two major activities namely recognition and response.
The presents volume (Volume I) comprises 2 blocks namely
Block 1: Introduction to Immunology
Block 2: Antigen–Antibody
Block 1 comprises five units and Block 2 consists of three units in all.
Unit 1 “Overview of the Immune System” gives an insight of historical perspective of

immunology. It introduces basic concepts of immunology i.e. self and non self regulation,
clonal selection theory and various categories of pathogens. Various types of pathogens,
pathogen associated molecular patterns (PAMPs) and host-pathogen interactions are
discussed here.
Unit 2 and 3 speak of non specific and specific lines of defence of the body i.e. innate and
adaptive immunity respectively. Innate immunity is inborn immunity to certain infection prior
to exposure of that disease. Innate immune system serves as the first line of defence by
creating anatomical, humoral and cellular barriers.
Unlike innate immunity, adaptive immunity has the ability to recognise specific antigens,
develop memory and ability to distinguish between self and non self. Adaptive immunity can
be humoral and cell mediated immunity.
Units 4 and 5 explain about cells and organs of immune system. In Unit 4, you will study
about primary lymphoid organs (where immune cells develop i.e. bone marrow and thymus)
and secondary lymphoid organs (where the immune response is initiated i.e. lymph node,
spleen, MALT). Cells of myeloid lineage i.e. granulocytes (neutrophils, eosinophils,
basophils, mast cells), Phagocytic cells (monocytes macrophages and dendritic cells) and
cells of the lymphoid lineage that include lymphocytes (B and T cells– CD4 and CD8) and
natural killer cells (NK cells) are discussed in Unit 5.
Block 2 – “Antigen–Antibody” comprises four units. Unit 6 “Antigens” explains about general
structure, basic properties of and various types of antigens viz. autoantigens, alloantigens,
exogenous and endogenous antigens.
Unit 7 explains about antibodies (Immunoglobulins Igs). Their basic structure and classes
(IgG, IgM, IgA, IgE and IgD) are discussed in Unit 7. It speaks about various immunoglobulin
variants i.e. isotypes, allotypes and idiotypes. Monoclonal and polyclonal antibodies are
discussed and their differences are also explained. 9
In Unit 8 you will study about mechanisms of antigen-antibody interaction (i.e. precipitation,
agglutination, neutralization complement fixation and opsonisation). Basic immunological
tools i.e. Western Blot ELISA, flow cytometry and others are also discussed.
Objectives
After studying this block you will be able to:
• trace the course of development of the field of immunology,
• define innate immunity and list the various innate immunity barriers,
• define Toll like Receptors,
• discuss the functions of NK cells,
• define complement system, list its functions and explain various complement activation
pathways,
• gain an insight about the adaptive immune system and list the various features of
adaptive immunity,
• differentiate between humoral and cell-mediated immunity,
• explain the role of NK cells as a bridge between innate and adaptive immune systems,
• compare and differentiate functions executed by primary and secondary lymphoid

organs
• discuss the process of generation, regulation and functions of immune cells,
• explain mechanism of immune responses, and
• discuss the properties of Antigen Recognized by the B and T cells,
10
Unit 1 Overview of the Immune System
UNIT 1
OVERVIEW OF THE IMMUNE
SYSTEM
Structure
1.1 Introduction The Postulates of Clonal
Selection Theory
Objectives
1.5 Introduction to Pathogens
1.2 Historical Perspective of
Immunology 1.6 Major Categories of Human
Pathogens
1.3 Introduction to Basic
Concepts of Immunology Virus
The Innate Immune System Bacteria
The Adaptive Immune System Protozoa
Humoral Immunity Helminths or Parasitic Worms
Cell Mediated Immune 1.7 Host-Pathogen Interaction

Response
Interaction with the Innate
Antigen Processing Immune System
Exogenous Antigen Processing Mechanisms used by Pathogens

to Evade Adaptive Immune
Endogenous Antigen Processing
Response Mediated Killing
1.4 Self and Non-Self Cells
1.8 Summary
Tolerance
1.9 Terminal questions
Autoimmunity
1.10 Answers
Clonal Selection Theory
1.1 INTRODUCTION
Immunology is the study of the functioning of immune system. Immune system
is a defence system that protects us from invasion by pathogens. Diseases
like allergy, autoimmunity and cancer can result if the immune system fails to
work properly. The immune system has two components called the innate and
adaptive immune system. Adaptive immune system is further divided into
Humoral and Cell Mediated Immune Systems. Together these systems work
to protect the body. 11
Block 1 Introduction to Immunology
One of the most important characteristics of immune system is the ability to
distinguish between self and foreign (cells and molecules). The cells that bind
to self-antigens are selectively eliminated during the early developmental
stages. Only activated cells that bind to foreign antigens are clonally
selected and propagated.
This unit also talks about infectious agents called pathogens that attack the
body. These pathogens belong to very diverse classes like bacteria, fungi,
protozoa, viruses and helminths. The immune system must combat these
pathogens and prevent the establishment of infection in the body through
various host-pathogen interactions.
The concepts that are being discussed in this unit will be dealt in detail in
further Units of this course: You are being introduced to some immunological
terminology that will be used throughout this course.
Objectives
After studying this unit, you should be able to:
 trace the course of development of the field of immunology,
 explain an overview of the immune system,
 discuss how the body differentiates between self and foreign molecules,
 explain the basic causes of autoimmunity,
 list the postulates of Clonal Selection theory,
 explain basic terms like pathogenicity and transmission,
 list the various classes of human pathogens, and
 give examples of major pathogenic diseases.
1.2 HISTORICAL PERSPECTIVE OF

IMMUNOLOGY
• The term ‘Immunity’ comes from the Latin word ‘ímmunis’ that means to
exempt. Thus immunity refers to a state of protection from disease.
• Thucydides in 430BC while describing a plague in Athens introduced the

concept of immunity for the first time.
• Chinese and Turks made the first attempts to provide immunity in the
fifteenth century.
• Lady Mary Wortley Montagu observed in 1718 the advantages of

variolation of the local population and got her children variolated. In this
technique, dried crust from the dried pus of small pox patients has been
given to subjects via small cuts or inhalation.
• Edward Jenner, an English physician in 1789 went on to improve this

12 technique. He was surprised to note that the milkmaids who had
previously been infected with cowpox were subsequently found to be
immune to smallpox. Jenner concluded that inoculating fluid from
cowpox pustules into subjects might protect them from smallpox.
• The next discovery made by Louis Pasteur was a fortunate happening.

He had successfully grown the fowl cholera causing bacteria in culture
and had then demonstrated that when chickens were injected with that
cultured fowl cholera causing bacterium, they developed cholera. He
then went on a vacation and could not revive the culture. On returning
from the vacation, Pasteur injected the chickens with the old culture and
found that the chickens just became ill, but they soon recovered. He
then intended to repeat the experiment with a freshly grown culture but
due to a limited supply of chickens, he had to inject the same chickens
with the fresh culture. To his surprise, the chickens again fell ill and
recovered.
Thus, Pasteur put forward the hypothesis that aging of the culture had
dampened the virulence of the bacteria. He said that such attenuated
pathogen might be administered to individuals to provide protection
against the disease. He coined the term ‘vaccine’ for this attenuated
pathogen (Latin: ‘vacca’ means cow), to honour the work of Edward
Jenner in cowpox inoculation to protect against smallpox.
• The first vaccine was administered by Pasteur in 1885 to a young boy

named Joseph Meister who had been severely bitten by a rabid dog.
Several doses of attenuated rabies viral preparations were given to the
boy and thus he was protected from rabies.
• The first insight to the working mechanism of immunity was established

by the work of Emil von Behring and Shibasaburo Kitasato in 1890. They
showed that immunity against diphtheria could be transferred from
immunised patient via serum to non-immunised individual.
• During the next decade, terms like precipitin, antitoxin and agglutinin
popped up to indicate the component of serum that performed the roles
of clumping bacteria and neutralising toxins. They were all considered to
be separate components till Elvin Kabat attributed all these functions to
an immunoglobulin molecule. These are now known as antibodies.
• The immunity mediated via these antibodies present in the serum was
thus called as humoral immunity.
• Elie Metchnikoff observed that certain cells which he called phagocytes

were white blood cells that were able to internalise (phago/endocytose)
microbes and other foreign material. He observed that the phagocytic
cells were more active in immunized animals and thus he hypothesized
that cells were more important for immunity than the serum components.
The cells identified as active phagocytic cells were monocytes and
neutrophils.
• For a long time the scientists were divided between the humoral and the
cell mediated immunity theories. However, it was established later that
both work together in the body. 13
• Interest in cell-mediated immunity was renewed when Merill Chase
successfully transferred immunity against pathogen causing tuberculosis
while performing a leukocyte transfer experiment on pigs.
• The lymphocyte was identified in 1950s as an important element of

humoral and cell mediated immunity.
• Bruce Glick demonstrated via his experiment on chickens that cell

mediated immunity was effected by T-cells and humoral immunity by B-
cells.
SAQ 1
Fill in the blanks:
a) Variolation was first performed by …………………. on her children.
b) ……………………. observed the phenomenon of phagocytosis for the

first time.
1.3 INTRODUCTION TO BASIC CONCEPTS OF

IMMUNOLOGY
The immune system is a defence system that protects animals against
attack by pathogens and cancer. A large number of cells and molecules are
produced by the immune system to perform this task.
The immune system has two major activities namely- recognition and
response.
• The ability to differentiate even single amino acid differences among

pathogens and also self from non-self (molecules and cells).
• Once pathogen recognition is complete, an effector response is mounted

to neutralize the pathogen or toxin. Subsequent exposure to the same
pathogen generates a more intensive memory response.
1.3.1 The Innate Immune system

It is the first line of defence of the body present from the time of birth. The
innate immunity components are present before the initiation of infection. It is
not specific for a particular pathogen but in general increases the ability of the
body to recognise commonly found molecules on the surface of pathogens.
Table 1.1 depicts various barriers and mechanisms of protection.
Table 1.1: Barriers and mechanisms of protection.
Sl. No. Barriers Mechanism of protection
1. Anatomical a) The skin has epidermis and dermis that

Barriers form a covering and prevent pathogen
invasion.
14
The low pH of secretions by sebaceous
and sweat glands is inhibitory to
pathogens.
b) Mucous membranes form a continuous

lining where pathogens are trapped in
mucous and are removed. Also, they have
to compete with the normal microflora of
the body for attachment sites.
2. Physiological a) Temperature-Fever protects against

Barriers pathogens.
The high body temperature of some

organisms protects them from diseases.
For example, chickens are protected from
B. anthracis due to their high body
temperature.
b) pH- Low pH of gastric secretions inhibits

most microbes.
c) Antimicrobial substances like lysozyme in

tears, saliva.
3. Phagocytic Phagocytic cells engulf, break down and kill the

Barriers pathogens. Examples are macrophages,
neutrophils, monocytes.
4. Inflammation There is leakage of fluid from blood vessels due

to vasodilation and increase in permeability.
There is an influx of cells to the area of pathogen
invasion/damage.
1.3.2 The Adaptive Immune System

Foreign pathogens and antigens are selectively recognised and eliminated by
the adaptive immune system when the innate immune system fails to defend
the body against the pathogen invasion. It is capable of responding only when
a stimulus is provided by the innate immune system.
The Adaptive or Acquired immune response takes much longer time

than the innate immune response to become activated and respond. It
can take days or even weeks but adaptive immunity is more pathogen specific
and also has memory. Adaptive immune response is generated post exposure
to a pathogenic antigen or after a vaccination. The responses are tailor made
to specific antigenic challenges and not present naturally like the innate
immune system.
The adaptive immunity can be naturally or artificially acquired:
• Naturally acquired immunity results when the body fights the pathogen
and recovers or when preformed antibodies are provided via the
placenta and mother’s milk. 15
• Artificially acquired immunity results when killed/attenuated pathogen or
toxoid is injected in the body. This process is called Vaccination.
1.3.3 Humoral Immunity

Humoral immunity depends on molecules found in the “humor”, that is the
body fluids. It is mediated by molecules like antibodies, various complement
proteins and antimicrobial peptides. Therefore, it is also as Antibody
Mediated Immunity.
Humoral immunity involves the production of antibodies and simultaneously

occurring events like the activation of helper T-cells and production of
cytokines. It also involves the various effector function of antibodies like-
• Neutralization of pathogens and toxins.

• Classical pathway of complement activation.
• Opsonisation (of pathogen) and phagocytosis.
• Eventual pathogen clearing.
1.3.4 Cell mediated Immune Response

Cell mediated immune response is the method of the body to fight against
pathogens like bacteria and viruses. It is also responsible for the killing of
cancerous cells and in the graft-rejection process.
The foreign antigen is recognised by phagocytic cells like macrophages and

dendritic cells of the innate immune system. They internalise the pathogen,
degrade it and present their antigenic peptides on their surface with MHC
Class II molecules. This MHC-antigenic complex is responsible for the
activation of adaptive immune system.
CD4+ and CD8+cells are formed from T-cell precursors in the thymus. The
MHC Class II complex on APCs (Antigen presenting cells) interact with the
CD4+ T cells while the CD8+ T cells interact with the antigen- Class I MHC
complex found on infected or cancerous cells. The CD8+ T cell transforms into
Cytotoxic T lymphocytes (CTL) that are responsible for the destruction of the
infected or the cancerous cell.
Table 1.2 describes the major cells involved and their important features.
Table 1.2: Cells and their features in immune response.

Sl. Cell Major features
No.
1. B-cell • Mature in bone marrow
• Express membrane bound

antibody molecules with
specificity to particular antigen.
• When naive B-cell encounters an

antigen, it is activated and
16 proliferates to form memory B-
cells and plasma cells.
• Plasma cells secrete antibodies

rapidly.
• Memory cells get activated on

subsequent exposure to the
same antigen and produce a
much more severe response.
2. T-cell • Formed in bone marrow but

matures in thymus.
• Express T-cell receptor (TCR) on

its surface.
• TCR can recognise antigen only

when bound to MHC molecules.
• Naive T-cell on encountering

MHC bound antigen proliferates
to produce effector T-cells and
memory T-cells.
• Helper T-cell (TH cell) on

activation secretes cytokines that
further activate cytotoxic T-cells
(Tc cells).
• Tc cells proliferate to form

cytotoxic T-lymphocytes (CTL)
that kill the pathogen.
3. Antigen presenting cells • Macrophages, dendritic cells and

B-lymphocytes.
• Express class II MHC molecules

on their surface.
• They internalise the antigen and

degrade it into smaller
fragments. The fragment is then
expressed with MHC-II
molecules on the surface.
• They provide co-stimulation

signal for TH cell activation.
1.3.5 Antigen Processing

The T-cell recognises antigen only after it is degraded into smaller peptides
that can form complexes with MHC Class I or II molecules. This process that
the antigen undergoes is called Antigen presentation and processing. The
route of antigen entry determines whether the antigen will be presented with
Class I or Class II MHC molecules. 17
Exogenous Antigen Processing
Exogenous antigen is taken up by the cell by phagocytosis or endocytosis and

degraded into smaller peptides. This process is performed by antigen
presenting cells like macrophages, dendritic cells and B-cells in the Endocytic
processing pathway.
The antigenic peptides produced are bound to MHC Class II molecules and
transported to the cell surface. Therefore the presentation of exogenous
peptides is limited to antigen presenting cells that bear MHC II molecules. Now
the CD4 displaying T-cells bind to MHC-II bound antigen. These cells act as
helper T-cells.
Endogenous Antigen Processing
Endogenous antigens are produced inside host cells. Common sources of

endogenous antigens are cancerous cells and virus infected cells that
continuously form viral proteins. They are degraded in the endoplasmic
reticulum to smaller fragments. These fragments bind with MHC-I molecules
and move to cell surface. Class I MHC-antigen complex is recognised by CD8
bearing T cells. These cells are killed by cytotoxic T-cells.
SAQ 2
State whether the following statements are ‘True’ or ‘False’:
a) T-cells are formed and mature in thymus.
b) Endogenous antigens are degraded to smaller fragments in

endoplasmic reticulum.
c) APCs express class I MHC molecules on their surface.
d) Humoral immunity provides protection against cancerous cells.
1.4 SELF AND NON-SELF CELLS

It is of critical importance that the immune system should differentiate body’s
own cells from foreign invaders. This is necessary to avoid attack on self-cells.
The immune system recognises the cells based on antigens present on the
surface. The microorganisms have antigens that are absent in the human
body and thus recognised as foreign.
The Major Histocompatibility Complex (MHC) is the major self-identification

molecule. Each individual has a unique combination of MHC molecules that is
recognised as self. When any difference is noted in these molecules in
pathogen infected cells, altered cancerous cells or in transplanted tissue, the
immune system is activated and attacks these cells.
The B-cells have antibodies attached on their surface that recognise and bind
to specific antigens on pathogen surfaces. The T-cell activation occurs via
antigen presenting cells (APCs) like macrophages. The pathogen is
internalised by APC, broken down and the fragment expressed with MHC
molecules present on the surface of APC. The T- cell binds to this presented
18 fragment via specific T-cell receptor (TCR) and this leads to T-cell activation
1.4.1 Tolerance
The ability of T and B cells to ignore or tolerate self-antigens is called as
Immunological tolerance. Tolerance involves selective elimination of self-
reactive cells during development. T-cells that bind to self-antigens are killed
in the thymus and likewise B-cells in bone marrow. The tolerance gained by
such mechanisms is called Central tolerance.
Therefore the immune system is able to develop cells with specificity to

antigen only through the process of tolerance and somatic recombination.
1.4.2 Autoimmunity
An autoimmune disease occurs when the body attacks its own self-cells
tissues and other body constituents. There are several reasons for the
development for autoimmunity-
1. The secretion of antibodies by plasma cells requires the activation of B-

cells by T-cells. But this need for T-cells can be neglected in certain
cases, example; super-antigens.
2. An imbalance between B and T cell functioning. For example; in coeliac

disease T-cells recognising gliadin activate B-cells recognising
transglutamine.
3. Damage in feedback mechanism mediated by B-cell receptor.
4. Dysregulation of cytokines.
5. Defective apoptosis of dendritic cell may lead to lymphocyte activation

and autoimmune conditions, since dendritic cells are antigen presenting
cells.
6. Molecular mimicry- the pathogen’s antigens closely resemble a molecule

in the host. Thus, immune response might be mounted on self-cells in
such cases.
SAQ 3
Fill in the blanks:
a) ………................. is an example of autoimmune disease.
b) The ability of T and B cells to ignore or tolerate self-antigens is called as

………................. .
1.5 THE CLONAL SELECTION THEORY

The Clonal Selection theory was put forward by Neils Jerne, F. Macfarlane
Burnet and David Talmadge.
Neils Jerne’s theory proposed that large amounts of antibodies are present in
the serum at all times. In the scenario of invasion by a pathogen, that antibody
is selected and produced in large quantities which have specificity for the
target antigen. 19
Burnet expanded Jerne’s theory in a paper titled “A modification of Jerne's
theory of antibody production using the concept of clonal selection”. He later
wrote a book called “The Clonal Selection Theory of Acquired immunity”
and postulated the theory of Clonal Selection.
The theory states that each lymphocyte expresses antigen specific membrane
receptors that are specific to a particular antigen. The receptor’s specificity for
a distinct antigen is determined even before the lymphocyte interacts with the
antigen. The interaction between the specific receptor and its corresponding
antigen causes the activation of B-cells in the secondary lymphoid organs
(spleen and bone marrow) where it encounters the antigen (Fig 1.1).The B-
cells then proliferate to form a clone of cells with the same antigen specificity
as the parent B-cell.
This is the currently accepted model for the immune response to foreign
antigens and selection of specific B and T cells to carry out the immune
effector functions.
Fig1.1: Clonal selection theory: B-cell specific to antigen is selected and

proliferates to form memory and plasma cells.
1.5.1 The Postulates of Clonal Selection Theory

• Each lymphocyte bears a receptor with specificity for a particular antigen.
• The activation of cell occurs only after interaction with that particular
antigen.
• A clone of cells is produced with identical antigen specificity as its parent
cell.
• Selective destruction of lymphocytes bearing endogenous antigens on
their receptors. This prevents the immune system from targeting self-
20 cells.
1.6 INTRODUCTION TO PATHOGENS
The term ‘pathogen’ comes from the Greek word “pathos” meaning suffering. Microbiology is the
Pathogen is an organism or an infectious agent that can cause disease. study of
microorganisms,
There can be several infectious agents like virus, bacteria, protozoan or including microscopic
fungus. Disease can also be caused by parasitic worms and insect larvae pathogens. The study
(Table 1.3). of parasites and their
hosts is called
Pathogenicity: It is the potential of a pathogen to cause disease. It is a Parasitology. The
qualitative term. The pathogenicity of a pathogen depends on several factors study of the diseases
like: caused by these
pathogens is called
• Ability to enter host tissue by Pathology.
• Colonise the host tissue
• Use the host nutrients
• Suppress the host immune system
• Ability to produce toxins
Transmission: The spread of pathogen. It occurs via several routes like

faeco-oral route, air, water, through direct and indirect contact, blood, body
secretions like milk, saliva and tears.
Table 1.3: Examples of common human pathogens and diseases caused

by them.
Sl. Pathogen group Name of pathogen Disease Caused

No.
1. Bacteria Klebsiella pneumonia Pneumonia

Baciilus anthracis Anthrax
Vibrio cholera Cholera
Mycobacterium Tuberculosis
tuberculosis
2. Virus Herpes simplex virus Herpes
Rhinovirus Common cold
Hepatitis virus Hepatitis
3. Protozoa Plasmodium sp Malaria

Leishmania donovani Leishmaniasis
4. Helminths Ascaris Ascariasis
Schistosoma Schistosomiasis
21
5. Fungi Candida albicans Candidiasis
Aspergillus flavus Aspergillosis
Dermophytes Athlete’s foot
1.7 MAJOR CATEGORIES OF HUMAN

PATHOGENS
A plethora of microorganisms are found in our surroundings and thus the
human body is susceptible to attack by many diverse groups of pathogens. A
few of them will be discussed here.
1.7.1 Virus
Virus is an infectious agent that is dependent on the host for its metabolic
activities and replication. Outside of the host cell, they exist as small inactive
particles called as ‘virions’.
The virion has:
1. Genetic material in the form of DNA/RNA but never both.
2. A protein coat (capsid) that protects the genetic material.
3. An envelope may also be present- Enveloped viruses.
Interaction of Virus with Innate Immune System
The innate immune system responds to viral infections by producing
Interferon is a protein
Interferons- IFNα and IFN- β and activation of Natural Killer (NK) cell
released by animal
activation. These Interferons bind to receptors called IFNα/β
IFN receptor and
cells, usually in
response to the entry
activate the JAK-STAT pathway. This goes on to cause the transcription of
of a virus, which has many genes whose products have many antiviral roles. For example, RNase L
the property of that degrades the RNA of the virus is activated by an enzyme called 2,5- oligo-
inhibiting virus adenylate-synthetase. This enzyme is a product of one of the activated genes.
replication.
Virus Neutralisation with Antibodies
Antibodies against specific antigens of the virus prevent viral spread and
protect against virus reinfection. Many viruses bind to the cell surface of the
host via specific molecules expressed on their surfaces. For example, Epstein
JAK-STAT Pathway Barr virus binds to B-cells via type II complement receptors. Antibodies that
is a chain of are targeted to these receptors would inhibit the binding of virus to the host
interactions between cell surface and thus prevent infection altogether.
proteins in a cell and
is involved in Agglutination of the virus can also occur by antibodies and complement
processes, such as proteins. This would promote virus phagocytosis by acting as opsonins.
immunity, cell division
and tumor formation. Virus clearance by Cell mediated immunity (Fig 1.3)
The innate immune responses are effective before the establishment of
infection, especially if the virus genome has integrated with the host genome.
Thus, cell-mediated immune systems are crucial in such scenarios.
The main defence components against viruses are CD8+TCcells and CD4+TH
cells. Various cytokines like TNF, IL-2 and IFN-γ are produced by activated
22 TH1 cells that directly or indirectly protect against the virus.
• IL-2 helps in bringing precursors of CTL (Cytotoxic T cells) into effector
population
• IFN-γ creates an antiviral state Epstein Barr Virus

(EBV) is the
• NK cells are activated by IFN-γ and IL-2 together. NK cells are important underlying pathogen
in providing protection against the virus in initial stages of the infection till of infectious
the CTLs are activated. mononucleosis, which
is a benign, self
limiting disease.
Opsonin is an
antibody or other
substance which
binds to foreign
microorganisms
making them more
susceptible to
phagocytosis.
Fig 1.2: The various responses generated to virus
1.7.2 Bacteria
Bacteria can gain entry into the body via cuts, breaks, wounds or through the
respiratory, gastrointestinal or genitourinary tracts. The response of immune
system depends on both the number of invading bacteria and their virulence-
• Lesser number of bacteria with low virulence are often dealt with tissue
macrophages.
• For larger numbers of bacteria with higher virulence, the response is
often by the adaptive immune system.
The flowchart (Fig 1.3) depicts the steps in establishment of bacterial infection:
Fig 1.3: The process of establishment of bacterial infection 23

Intracellular and Extracellular Bacteria
The main response for protection against extracellular bacteria is the humoral
immune response. Antibodies are secreted by plasma cells in lymph nodes
and in the submucosa of gastrointestinal and respiratory tracts.
Extracellular bacteria may secrete toxins (endotoxins/exotoxins) or effect a

local inflammation. The exotoxins are secreted out by the bacteria, like the
diphtheria toxin. The endotoxins are usually bacterial cell wall components,
like the LPS (lipopolysaccharide).
Protection against intracellular bacteria is provided by activation of NK cells.

Cell mediated immune responses are induced in the case of intracellular
bacteria, especially delayed type hypersensitivity. Cytokines like interferon-γ
secreted by CD4+ T cells activate macrophages. The activated macrophages
kill the pathogen effectively.
The antibodies can neutralise extracellular bacteria in many ways as shown in

Fig 1.4.
Fig 1.4: The various neutralisation mechanisms of bacteria by antibodies
1.7.3 Protozoa
Protozoa are single celled eukaryotes that are responsible for causing many
human diseases like Leishmaniasis, toxoplasmosis, malaria, African sleeping
sickness and Chaga’s disease.
The location of the protozoa in the body determines the type and effectiveness
of immune response developed.
The humoral immunity mostly works against the protozoa in the stages
of its lifecycle where they freely move in the blood stream. On the other
hand, the cell mediated immunity is most effective in stages where the
organism shows intracellular growth.
1.7.4 Helminths or Parasitic Worms

They are large, multicellular worms that are not intracellular pathogens. They
24 reside in the human body but do not normally reproduce there. Although their
larger size makes them more susceptible to the immune attack but often the
immune response is poor. Thus once the infection is established, it is often
difficult for the immune system to eliminate these parasites.
Helminths cause a variety of diseases in both animals and humans.
1. Ascaris – Roundworms present in the small intestine that cause

Ascariasis.
2. Schistosoma: chronic, debilitating disease called Schistosomiasis is

caused by it. The major pathogens in humans are:
• S. japonicum.
• S. mansoni.
• S. haematobium.
3. Pathogens of animals can sometimes also infect humans.
• Taenia- tapeworm that infects cattle, pigs.
• Trichinella- roundworm that is found in pigs.
SAQ 4
Fill in the blanks:
a) Diptheria toxin is an ………………….. .
b) B-cell activation takes place in the ……………………….. where it

encounters the antigen.
c) ………………….. are roundworms present in the small intestine that

cause Ascariasis
d) The endotoxins are usually bacterial cell wall components, like the
…………………..., ………………….. .
1.8 HOST- PATHOGEN INTERACTION

A pathogen must be able to evade the innate and adaptive immune systems if
it has to affect the host and cause infection.
1.8.1 Interaction with the Innate immune system

i) The innate immunity provides a primary effective barrier to the pathogen
in the form of skin and mucosal surfaces. This physical barrier is very
difficult for the pathogen to invade through the skin and gain entry.
ii) Additionally, many antimicrobial substances are also secreted by the

epithelial cells. For example, the stomach epithelial cells secrete
hydrochloric acid which is inhibitory to most microorganisms.
iii) The alternative complement pathway is activated by many microbial

molecules like, the peptidoglycan of bacteria. There is opsonisation of
the pathogen by the generation of C3b and thus enhanced phagocytosis
is seen. 25
iv) Macrophages or endothelial cells produce cytokines (like TNF-α, IL-1 )
when stimulated by endotoxins. This leads to further activation of
macrophages.
v) The pathogen is phagocytosed by phagocytic cells like macrophages.
vi) Antiviral response due to the production of interferons.
1.8.2 Mechanisms used by Pathogens to Evade

Adaptive Immune Response Mediated Killing
i). Pathogens shed their antigens or grow inside host cells where they are
safe from immune detection. By this mechanism they reduce their
antigenic potential.
ii). Pathogens mimic host cell surface molecules. For example, they may
gain membrane molecules with the same amino acids as the host
membrane molecules.
iii). Some pathogens regulate or selectively inhibit the immune responses.

This leads to an ineffective immune response against the pathogen.
iv). Some pathogens bring about variation in their surface molecules

continuously. This is achieved by either accumulating mutations
gradually or by a rapid change in the surface antigenic molecules.
1.9 SUMMARY
Let us summarise what you have learnt in this Unit:
• The immune system is a defence system that protects animals against

attack by pathogens and cancer.
• The body has innate and adaptive immune systems. The innate immune
system evolved earlier as it is also present in plants, earthworm and
insects. The presence of adaptive immunity is a unique feature of
vertebrates.
• The immune system has two major activities namely- recognition and
response.
• The innate immunity is the first, non-specific line of defence of the body
present from the time of birth whose components are present before the
initiation of infection.
• Foreign pathogens and antigens are selectively recognised and

eliminated by the adaptive immune system.
• The adaptive immune system further has humoral and cell mediated
immune systems.
• Self and non-self-recognition are important features of immune system.
• An autoimmune disease occurs when the body attacks its own self-cells
26 tissues and other body constituents.
• The ability of T and B cells to ignore or tolerate self-antigens is called as
Immunological tolerance.
• Clonal Selection Theory states that each lymphocyte expresses antigen

specific membrane receptor that is specific to a particular antigen. It
provides a mechanism for generation of diverse antibody specificities.
• The TH (helper) and TC (cytotoxic) cells are two subpopulations of T

lymphocytes. Helper cells recognise antigen-MHCII complex which
regulates immune response by secreting cytokines. Cytotoxic T cells
display cytotoxic activity by recognising antigen-MHCI molecules.
• Endogenous antigens are degraded in endoplasmic reticulum and are

displayed with MHCI molecules.
• Exogenous antigens are phagocytosed by Antigen presenting cells and

they are then broken down to smaller fragments. These fragments are
then displayed on surface with MHCII molecules.
• The killing of endogenous pathogens occurs by cell mediated immune

system and that of exogenous antigens occurs by humoral system.
• Pathogen is an organism or an infectious agent that can cause disease.
• There are several human pathogens like bacteria, fungi, protozoa,

viruses and parasitic worms.
1.10 TERMINAL QUESTIONS

1. Fill in the blanks:
a) The Clonal Selection Theory was put forward by…………..,

……......., and ……………………
b) RNAse L that degrades the RNA of the virus is activated by an

enzyme called …………………………………………
c) Outside of the host cell, viruses exist as small inactive particles

called as…………….
2. Expand the following terms:
a) ADCC
b) MAC
3. Write the various steps in the establishment of bacterial infection.
4. State whether the following statements are ‘True’ or ‘False’
a) The main response for protection against extracellular bacteria is

the adaptive immune response.
b) Protection against intracellular bacteria is provided by activation of

NK cells
c) IFN-γ creates an antiprotozoan state
d) Helminths are not intracellular pathogens. 27

5. Fill in the blanks
a) …………………….virus binds to B-cells via type II complement

receptors.
b) Antibody toxin complex formed is cleared by …………………….
c) A chronic, debilitating disease called Schistosomiasis is caused

by……………………..
d) An ………………………….occurs when the body attacks its own

self-cells, tissues and other body constituents.
6. Match the following:
Column I Column II
i) Pneumonia a) Innate immunity
ii) Measles b) Exogenous antigen
iii) Endocytic pathway c) Bacterial disease
iv) Low pH d) Viral disease
7. Define the following terms:
a) Tolerance
b) Autoimmunity
c) Phagocytic barriers of innate immunity
d) Inflammation
8. Give an example of each of the following in the space provided-
Bacterial disease that can prevented

due to high body temperature
Protozoan disease
Autoimmune disorder
Cytokine
1.11 ANSWERS
Self Assessment Questions
1. a) Lady Mary Wortley Montagu
b) Elie Metchnikoff
2. a) False- only mature in thymus
b) True
28
c) False- ClassII MHC
d) Cell Mediated Immunity
3. a) Rheumatoid arthritis
b) Immunological tolerance.
4. a) Exotoxin
b) Secondary lymphoid organs (spleen and bone marrow)
c) Ascaris
d) LPS (lipopolysaccharide).
Terminal Questions
1. a) Neils Jerne, F.Macfarlane Burnet and David Talmadge.
b) 2,5- oligo-adenylate-synthetase.
c) Virions
2. a) Antibody dependent cell mediated cytotoxicity
b) Membrane attack complex
3. The various steps in the establishment of bacterial infection are-
• Invasion by bacteria
• Attachment of bacteria to host cells
• Bacterial proliferation
• Invasion of tissues of the host
• Damage to host tissues via various toxins.
4. a) False. It is humoral response
b) True
c) False. It creates an antiviral state
d) True
5. a) Epstein Barr virus
b) Phagocytic cells
c) Schistosoma
d) Autoimmune disease
6. i) c, ii) d, iii) b, iv) a.
29
7. a) The ability of T and B cells to ignore or tolerate self-antigens is
called as Immunological tolerance.
b) An autoimmune disease occurs when the body attacks its own

self-cells tissues and other body constituents.
c) Phagocytic cells engulf, break down and kill the pathogens.

Examples are macrophages, neutrophils, monocytes
d) In inflammation there is leakage of fluid from blood vessels due to

vasodilation and increase in permeability. There is an influx of cells
to the area of pathogen invasion/damage.
8.
Bacterial disease that can be Anthrax

prevented due to high body
temperature
Protozoan disease Malaria by Plasmodium
Autoimmune disorder Rheumatoid arthritis
30
Unit 2 Components of the Immune System-I
UNIT 2
COMPONENTS OF IMMUNE
SYSTEM
SYSTEMI
Structure
2.1. Introduction 2.4. Complement System
Objectives Functions of the Complement
2.2. Innate Immunity System
Anatomical Barriers The Classical Pathway
Physiological Barriers The Formation of Membrane

Attack Complex
Endocytic and Phagocytic
Barrier The Lectin Pathway
Inflammatory Barrier The Alternative Pathway
2.3. Pattern Recognition 2.5. Phagocytosis
PAMPs- Pathogen Associated 2.6. Inflammation

Molecular Patterns Types of Inflammation
PRRs- Pattern Recognition 2.7. Summary
Receptors 2.8. Terminal questions
Toll Like Receptors 2.9. Answers
Natural Killer Cells
2.1 INTRODUCTION
This unit aims to provide you with a picture of the non-specific pathogen
evasion mechanisms in our body. The innate immunity which is present from
birth is a natural defence system of our body that protects us from a variety of
pathogens on a daily basis. Most pathogen groups share similar molecular
patterns that can be recognised as foreign and an immediate response can be
mounted. As the pathogen enters the body, it is faced with many barriers like
the phagocytic and endocytic barriers, wherein the pathogen is engulfed and
lysed. The inflammatory response is a cascade of events that is triggered by
tissue damage due to a wound or pathogen invasion. This phenomenon
serves to remove the damaged cell, prevent further spread of the infection and
also promotes the healing process. You shall also come to know about the
Complement system that includes inactive proteins and zymogens circulating
in the blood, which are activated by several mechanisms on encountering the
pathogen. 31
Objectives
After going through this unit, you shall be able to-
 define innate immunity
 list the various innate immunity barriers,
 describe pattern recognition, Pathogens Associated Molecular Patterns

and the receptors involved in this process,
 define Toll like Receptors,
 discuss the functions of NK cells,
 define complement system and list its functions,
 explain various complement activation pathways,
 explain the mechanism of phagocytosis using flowchart,
 explain inflammation and list its types, and
 describe the mechanism of inflammation.
2.2 INNATE IMMUNITY

It is the first, non-specific line of defense of the body present from the
time of birth. The innate immunity components are present before the
initiation of infection. Innate immunity is not specific for a particular
pathogen but in general increases the ability of the body to recognise
commonly found molecules on the surface of pathogens. Fig 2.1 depicts
the various types of barriers viz. anatomical, inflammatory, physiological
and phagocytic which provide immunity to the humans.
Fig: 2.1: Various barriers that provide immunity.
2.2.1 Anatomical Barriers

It includes skin and mucous membranes of the body. It acts as a primary
32 physical barrier that prevents the entry of microorganisms.
1. Skin: The skin of the body is the largest organ and thus serves as a
primary barrier. It has two layers- Epidermis and Dermis.
Epidermis is the thin outer layer made of dead cells and has keratin
deposition, while the dermis is thicker and has connective tissue, blood
vessels and sebaceous and sweat glands. The sebum produced has a
low pH around 3-5 and thus effectively prevents the growth of
microorganisms.
However, the pathogens may breach the skin via cuts, wounds and
other aberrations.
2. Mucous membranes: The mucous membranes line the conjunctiva,

respiratory, gastro-intestinal and the urogenital tracts of the body. It has
a number of defence elements like saliva, tears and mucous secretions
that wash off pathogens and also have antimicrobial activity, i.e. kill the
pathogens.
Mucous is the viscous fluid secreted by the epithelial cells of the

mucous membranes that serves to trap the pathogens.
2.2.2 Physiological Barriers

Include temperature, pH and other soluble and cell associated molecules.
1. Temperature: The normal body temperature discourages the growth of

most pathogens. For example the high body temperature of chickens
provides them immunity for anthrax.
2. pH: Microorganisms are very sensitive to pH changes and each microbe

has its optimum pH of growth.
The highly acidic pH of the stomach inhibits the growth of most

microorganisms. Also the low pH of sebum discourages microbial
growth.
3. Soluble and cell associated molecules: Various molecules circulate in

the body that serve as antimicrobial agents. These molecules and their
activity are given in Table 2.1.
Table 2.1: Activity of various antimicrobial agents.
Sr. Molecule Activity

No.
1. Lysozyme Found in tears, saliva and other mucous membrane

secretions. It cleaves peptidoglycan of bacterial cell
walls and thus eliminates pathogens.
2. Interferon Creates an antiviral state in the body.
3. Complement Circulating inactive proteins that may be activated by

formation of antigen-antibody complexes or by
reactions between complement proteins and cell
wall components of pathogen.
33
2.2.3 Phagocytic and Endocytic Barriers
This serves as the next line of defense for those pathogens that have
managed to cross the epithelial cell barriers. Endocytosis is the uptake or
engulfment of foreign material by the cell, as carried out in Amoeba.
Phagocytosis is a type of endocytosis carried out by macrophages,
neutrophils, dendritic cells and monocytes.
2.2.4 Inflammatory Barriers

It comes into play when tissue damage occurs due to a wound or in events of
pathogen invasion. It is a cascade of events. It is one of the earliest responses
to infection or irritation. This is stimulated by factors secreted by damaged
cells and helps to prevent spread of infection.
Thus we conclude that anatomical and physiological barriers form the

physical barriers while phagocytic and inflammatory barriers form the
chemical barriers.
SAQ 1
Fill in the blanks:
a) The …………………… line the conjunctiva, respiratory, gastro-intestinal

and the urogenital tracts of the body.
b) The antimicrobial substance in tear and saliva is ………………… .
c) Physical barriers include ……………………. and …………………….

Barriers.
d) ……………………of sebum discourages microbial growth.
e) Lysozyme cleaves ………………… of bacterial cell wall.
2.3 PATTERN RECOGNITION

It is the ability of the immune system to recognise a class of molecules that are
uniquely found in microorganisms and never in multicellular hosts. The innate
immune system is capable of recognising such molecules and fight with the
invading pathogens based on it.
The molecules capable of pattern recognition can be soluble or cell associated

receptors. The complement system involves circulating soluble molecules
capable of identifying microbial patterns. In the following subsections, you will
study about various types of receptors.
2.3.1 PAMPs- Pathogen Associated Molecular Patterns

They are sugar, protein or nucleic acid motifs present in multiple copies on the
surface of bacteria, fungi, viruses and other parasites. They help in the
34 identification of pathogen by the immune system.
2.3.2 PRRs- Pattern Recognition Receptors
These are the host receptors that recognise the Pathogen Associated Mannans are
Molecular Patterns. Some PRRs bind the microbe PAMPs like mannans, polysaccharides that
lipopolysaccharides and peptidoglycan and induce phagocytosis. are linear polymers of
the sugar mannose.
PRRs can be found on plasma membrane or in endolysosomes and in cytosol. Plant mannans have
This facilitates identification of both intracellular and extracellular pathogens. β 1-4 linkages.
Example of PRRs are: Mannan may also
refer to cell wall
1. LLRs- L Type Lectin Receptors polysaccharide found
• Mannose Receptor binds to mannans present on bacterial, fungal and in yeasts.
parasitic surfaces.
• Dectin-1 binds to β- glucans present on fungal cells.

2. Scavenger Receptors
• SR-A receptor binds to lipopolysaccharides (LPS), lipoteichoic acid

(LTA).
2.3.3 Toll Like Receptors(TLRs)

The first Toll protein was reported in the fruit fly Drosophila melanogasterby
Christiane Nüsslein-Volhard and Eric Wieschaus in 1985 and since then 10
TLRs(TLR1–TLR10) have been discovered in humans and 13 (TLR1–TLR13)
in mouse.
TLR (Toll-like receptors)are a class of pattern recognition receptors (PRRs)
that sense conserved molecular patterns for early recognition of pathogen by
initiating innate immune response. They detect a wide variety of patterns
associated with pathogens like viruses, bacteria, fungi and parasites as well as
damaged tissues.
TLRs are trans membrane proteins (Type I) having three structural domains
(Fig 2.2):
1. LRRs -Leucine-rich repeats motif. It helps in the recognition of pathogen.
2. A trans membrane domain.
3. Cytoplasmic Toll/IL-1 receptor (TIR) domain- It initiates signalling by
interacting with signal transduction adaptors.
Fig 2.2: The structure of Toll Like Receptors. 35

Most mammalian species contain the same set of TLR homologs but some
exceptions do exist.
They are found widely on leucocyte membranes, on antigen presenting cells

like dendritic cells and macrophages, on Natural killer (NK) cells (you will study
about NK cells in detail in the following subsection), T cells and B cells (cells of
adaptive immunity) and even on normal cells like fibroblasts, epithelial and
endothelial cells.
Upon activation, TLRs stimulate the antigen-induced signal transduction

pathway by recruiting adaptor proteins in cytosol of the immune cell. Adaptor
proteins serve to mediate other protein-protein interactions and then cause the
activation of other downstream proteins, like protein kinases
(TBK1,IKKi).These downstream proteins further amplify the signal and finally
lead to the suppression or upregulation of the genes that carry out the
inflammatory responses and other related transcriptional events. Often these
events eventually lead to cytokine production and proliferation of cells or
enhanced adaptive immunity.
If the TLR identifies a factor on bacteria, it is phagocytosed, digested and the

antigen are presented to CD4+ T cells. The infected cell may shut down its
growth and protein synthesis activity and undergo apoptosis (programmed cell
death) if a viral PAMP is identified.
Table 2.2 given below gives the list of a few important TLRs.
Table 2.2: Important Toll Like Receptors (TLRs).
Profillin is an actin Sr. Toll Like Location Ligand identified

binding protein No. Receptor
involved in the
dynamic turnover and 1. TLR1 Cell surface Triacylated lipopeptides
reconstruction of the
actin cytoskeleton. It 2. TLR2 Cell surface proteolipids, glycolipids,
is found in all lipoteichoic acid, zymosan
eucaryotic organisms
in most cells. 3. TLR3 Cell compartment Double stranded RNA
(endosome)
4. TLR4 Cell surface Lipopolysaccharide,

Virion is an entire
virus particle
lipoteichoic acid, heparin
consisting of an outer sulphate fragments, mannans
protein shell (capsid)
5. TLR5 Cell surface Bacterial flagellin, profillin
and inner core of
nucleic acid (RNA or
DNA).. 2.3.4 Natural Killer cells (NK cells)
NK cells are large granular lymphocytes that are naturally cytotoxic to tumor
cells even in the absence of previous immunisation to the tumor. It became
clearer later that NK cells are a separate lymphocyte lineage with roles like
cytotoxicity and cytokine-producing effector functions. They comprise around
5-10% of the lymphocytes in the body.
They play a crucial role in killing of virus infected cells in the body, graft
rejection mechanisms, controlling early signs of cancer and are also found in
36 the placenta during pregnancy.
They contain granules in the cytoplasm that contain lytic enzymes like
granzymes and perforins. When such molecules are released in proximity to
the infected cell, perforins create pores in the plasma membrane and allow
entry of granzymes and other enzymes, thus the cell undergoes apoptosis.
Apoptosis is required because lysis of the cell would release the virions and
further infect more cells, whereas apoptosis would terminate the virus within
the cell itself.
Cytokines like IFNγ and TNFα are also secreted by NK cells. These cytokines
act on macrophages and dendritic cells that further enhance the immune
response.
NK cells constantly come in contact with many cells and act as surveillance
system. Activating and inhibitory receptors are present on the surface of NK
cells and a balance of signals from these receptors decides whether or not a
cell will be killed by NK cell. Molecules expressed on the surface of infected
cells and cancer cells provide positive signals to activating receptors and
therefore activate the NK cells. The killing activity of NK cells is checked by
signals from inhibitory receptors. Class I MHC molecules are expressed on
most normal and healthy cells of the body and these cells are recognised as
‘self’. These MHC I molecules are recognised by inhibitory receptors on NK
cells that inactivate the NK cells and prevent them from killing any healthy cell.
Often infected and cancerous cells lose the MHC I molecules and thus their
self-tag. This makes these cells prone and susceptible to killing by NK cells.
Perforins and granzymes are released once a cell is marked to be killed by NK
cell. This function is important as most immune cells like T-lymphocyte cells
are not capable of recognising and eliminating cells with missing MHC class I
molecules.
The presence of CD56 and the absence of CD3 (CD56+, CD3−) help in the
identification of NK cells.
Functions of NK cells
1. Apoptosis via Cytolytic granules
They contain granules in the cytoplasm that contain lytic enzymes like
granzymes and perforins. When such molecules are released in
proximity to the infected cell, perforins (cytoplasmic toxic granules)
create pores in the plasma membrane and allow entry of granzymes and
other enzymes, thus the cell undergoes apoptosis. Granzymes are
serine-proteases that are stored as granules that depend on perforins for
delivery to target site. They effectively induce apoptosis in cooperation
with perforins.
2. Antibody dependent cell-mediated cytotoxicity (ADCC)
It involves the killing of target tumor or infected cell by NK cells with the
help of recognition of antitumor/antiviral antibodies produced in response
to the antigen on the target cell. The flowchart (Fig 2.3) and (Fig 2.4)
depict this process. 37
Fig 2.3: Flow chart to depict functions of NK cells.
Fig 2.4: Cell killing by ADCC.
3. Surveillance for presence of tumor cells.
NK cells are considered as part of innate immunity since NK cells lack

antigen-specific receptors and even target cells without prior exposure to
the antigen. This is important as T-cells and other immune cells are
unable to recognise cells in the absence of antigens. Once, NK cells
recognise tumor cells, cytokines like Tumor Necrosis Factor-α (TNF-α)
and Interferon γ (INF-γ)) are released to enhance immune response.
38 Before proceeding further, try to attempt the following SAQ.
SAQ 2
a) State whether the following statements are True or False.
i) PAMPs are proteins present in multiple copies on the surface of

pathogen.
ii) Nucleic acid cannot be recognised by any PRR.
iii) TLR is a pattern recognition receptor.
b) Match the following
Column A Column B
a) TLR3 i) PRR
b) Scavenger receptor ii) NK cells
c) Apoptosis via cytolytic granules iii) Single stranded RNA
2.4 COMPLEMENT SYSTEM

The term “complement” was coined by Paul Ehrlich for the activity of blood
serum that serves to complete the action of antibodies.
Complement system are group of soluble and cell bound proteins mostly
glycoproteins that are synthesized by liver hepatocytes, gastro-
intestinal, genitourinary tract epithelial cells, monocytes and
macrophages. They circulate in the serum as inactive proenzymes (also
called zymogens) and post proteolytic cleavage of inhibitory fragment, the
active site is exposed and they change into active molecules. Thus, the
complement system or the complement cascade involves a part of immune
system that helps antibodies and various immune cells to defend the body
against pathogens by promoting inflammation and attacking pathogen’s cell
membrane.
2.4.1 Functions of complement system

Complement system performs the following functions:
• Causes lysis of cells, pathogens like bacteria and viruses.
• Promotes phagocytosis of various particulate antigens via opsonisation.
• Complement receptors bind to many cells of the immune system. This

triggers specific cell functions, causes inflammation and subsequent
release of immune- regulatory substances.
• It also helps in the clearance of immune complexes from the body. 39

There are three established pathways of complement activation namely-
1. The Classical pathway
2. The Alternative pathway
3. The Lectin pathway.
2.4.2 The Classical Pathway

This pathway begins by the formation of a soluble antigen complex with
by the binding of an antibody to an antigen present on a target, for
antibody or by
example a bacterium.
It is important to note here that there exists a C1 macromolecular complex that

is involved in the initiation step (Fig 2.5).
Fig 2.5: The structure of C1 macromolecular complex.
The C1 macromolecular complex has three elements- 6 units of C1q, 2 units of

C1r and 2 units of C1s. This C1 complex binds by its globular heads to atleast 2
Fc sites on the antibody for stable C1 complex-antibody interaction (Fig. 2.6 and
Fig. 2.7).
40 Fig 2.6: The Classical Pathway of Complement Activation.

Fig 2.7: Flowchart representing the Classical Pathway.
2.4.3 The Formation of Membrane Attack Complex

(MAC)
C5b, C6, C7, C8 and C9 proteins interact to form the MAC. The MAC forms a
large pore in the plasma membrane of the target cells that leads to free
diffusion of ions.
The C5b formed by cleavage via C5 convertase provides an attachment site

for the other components of MAC. C5b is unstable and requires the binding of
C6 for stabilisation. Further C5b6 binds to C7 and the complex now has
hydrophobic areas exposed that would allow the insertion in the plasma
membrane of the target cell.
C5b67 attaches to C8 and the C5b67-C8 complex attached to cells and

creates a pore of 10angstrom diameter. But this is just sufficient to lyse red
blood cells but not pathogens. Thus, the involvement of C9 is crucial. About
10-17 molecules of perforin like C9 molecules form a complex capable of
insertion in pathogen membranes.
Therefore, the completed Membrane Attack Complex consists of C5b67-C8

complex surrounded by a perforin like poly C9 complex. The MAC is capable
of killing a variety of cells including Red Blood cells, nucleated cells, bacteria,
viruses and parasites.
2.4.4 The Lectin Pathway (Mannan Binding

Lectin Pathway)
The Lectin pathway is part of the innate immune system as it does not need
the formation of antigen-antibody complex for its activation. Pathogens like
Salmonella, Candida albicans, Listeria have mannose residues on the
carbohydrates or glycoproteins present on their surface. These mannose
residues bind to mannose- binding lectin (MBL) and thus lead to the activation
of the Lectin pathway.
Mannose Binding Lectin (MBL) is produced in inflammation as it is an acute

phase protein. MASP1 and MASP2 (Mannose associated serine- proteases)
bind to MBL and the complex so formed leads to the cleavage of C2 and C4
proteins (Fig 2.8). 41
The further steps are similar to the Classical pathway of complement
activation, which you have studied in subsec. 2.4.2
Fig 2.8: The Lectin Pathway.
2.4.5 The Alternative Pathway
The alternative pathway does not need the formation of antigen-antibody

complex for its activation. It is initiated by molecules present on pathogen that
are foreign to the host. Alternative pathway can be activated by cell wall
components from both Gram positive and negative bacteria. Therefore, it is
often considered as part of innate immune system. Figs. 2.9 and 2.10 depict
the mechanism of Alternative Pathway.
42 Fig 2.9: The Alternative Pathway.

Fig 2.10: Flowchart representing the Alternative Pathway.
SAQ 3
State true or false
i) The alternative pathway is a part of the innate immune system as it does

not need the formation of antigen-antibody complex for its activation.
ii) The MAC forms a large pore in the plasma membrane of the target cells
that leads to cell division disruption.
iii) Promotes phagocytosis of various particulate antigens via opsonisation.
SAQ 4
Fill in the blanks
a) The term “complement” was coined by …………………… .
b) Binding of C3b exposes site on ……………………. that allows binding of

Factor D.
c) The C1 macromolecular complex has three elements- 6 units of ……….,

2 units of …………… and 2 units of ……………. .
d) MASP1 and MASP2 (Mannose associated serine- proteases) bind to

……………………… and the complex so formed leads to the cleavage of
C2 and C4 proteins in the Lectin pathway.
43
2.5 PHAGOCYTOSIS
Cells internalise solid matter like pathogens by a special type of endocytosis
called as Phagocytosis. Many cells of the body are capable of performing
this task but it is best accomplished by cells called Professional antigen
presenting cells that include macrophages, immature dendritic cells and
neutrophils. Fig 2.11 and Fig 2.12 depicts the process of phagocytosis.
Fig 2.11: Flowchart representing the process of Phagocytosis.
Phagocytosis is an important part of the innate immunity as it does not

require antigen specificity and also serves to activate the adaptive immune
response. It not only helps to contain and kill pathogen but also in processing
antigens for further immune processes.
A number of receptors are involved in the phagocytosis process. This

includes the complement receptors and the Fc receptors that serve to help in
the phagocytosis of the opsonised pathogen.
pathogen. Other receptors like Toll like
Receptors, Lectin and Scavenger receptors are also important in pathogen
uptake.
44 Fig 2.12: Process of Phagocytosis.

2.6 INFLAMMATION
The inflammatory response is a cascade of events that is triggered by
damaged tissue due to a wound or pathogen invasion. It is a protective
response of the body that involves several elements like immune cells, blood
vessels and various molecular mediators. Inflammation is a part of innate
immune response as it does not involve pathogen specific mechanisms like
adaptive immunity but is a rather generalized response.
The inflammation process takes place to eliminate the cause of infection,

remove the damaged tissue and also initiate the healing process of the wound
or damage. Important signs of inflammation are given in Fig 2.13
Fig 2.14: The five Cardinal Signs of Inflammation.
2.6.1 Types of Inflammation

There are two types of inflammations.
1. Acute inflammation short term (lasts for a few days), triggered

immediately after injury of pathogen invasion. Microbial pathogens are
recognised by Toll Like receptors (TLRs). Neutrophils and macrophages
migrate to the site of inflammation under the influence of cytokines and
chemokines.
Acute inflammation is therefore the primary line of defense against

pathogen invasion. It is often initiated by resident macrophages,
dendritic cells and mast cells that recognise via PRRs, various PAMPs
(Pathogen associated molecular patterns) and DAMPs (Damage
associated molecular patterns).
Causes of acute inflammation include pathogens, toxins, allergens,

burns and frostbites. Sub -acute inflammation lasts longer from 2 to 6
weeks.
2. Chronic inflammation prolonged, which lasts for months to years.

Macrophages, plasma cells and lymphocytes are the primary cells 45
involved. Several diseases like allergies, cardiovascular diseases,
diabetes and COPD- chronic obstructive pulmonary disease are caused
by chronic inflammation.
It is also associated with conditions like hay fever and atherosclerosis.

Differences between these two inflammations are provided in Table 2.3.
Table 2.3 Differences between Acute and Chronic inflammation.
Sr. Acute Inflammation Chronic inflammation

No.
1. Lasts for a few days. Prolonged inflammation- months

to years.
Sub-acute inflammation may
last for 2-6 weeks.
2. Neutrophils are primarily Mainly involves macrophages,

involved lymphocytes and monocytes.
3. Little or no fibrosis is seen Marked fibrosis
4. Immediately occurs post Takes time to develop

wound/injury
5. Eicosanoids and vasoactive Involves cytokine growth factors,

amines are mediators hydrolytic enzymes and reactive
oxygen species
6. There is eventual healing. It may lead to fibrosis and tissue

destruction.
Now we will discuss about various events that take place during inflammation.
Events in Inflammation process
1. Vasodilation: This involves an increase in the diameter and

permeability of blood vessels that allows more blood flow at the site of
damage or injury. The redness in tissue and increase in temperature at
the site of inflammation that begins in the arterioles and eventually leads
to engorging of capillaries. The plasma moves out due to the increased
permeability of blood vessels that results in larger concentration of cells
which enlarge the blood vessels.
2. Increase in capillary permeability: This helps in the movement of fluid

from enlarged capillaries into the tissue spaces.
There is fluid accumulation that causes oedema.
3. Influx of phagocytes: Influx of phagocytes occurs at the inflammation

site due to increased permeability of capillaries.
46 The flowchart illustrates the process of influx of phagocytes (Fig 2.14).

Fig 2.14: Process of Influx of phagocytes.
Chemical Mediators of Inflammation
The chemical mediators of inflammation may be derived from various sources:
• Mediators produced locally by cells at the site of inflammation.
• Mediators sourced from plasma. These are formed in the liver.
• Some mediators are also produced by necrotic cells.
These mediators bind to specific receptors on target cells and bring about their
effects. Mediators like lysosomal proteases have direct toxic activity, while
some mediators may stimulate the secretion of secondary effector molecules
from target cells.
1. Cell Derived Inflammation Mediators
Activated cells (like mast cells) often secrete molecules (like histamine).
A variety of molecules may be secreted rapidly by mast cells (Fig 2.15),
macrophages and endothelial cells. A few of them have been listed
below:
• Histamine: It is rapidly secreted by mast cells, basophils and

platelets and causes increased vascular permeability and arteriolar
dilation. This increased permeability allows the influx of leucocytes
that are capable of combatting with the pathogen effectively.
Histamine release occurs when an antigen binds to an IgE

antibody present on the surface of mast cells or basophils.
It is responsible for itching and pain of the site of inflammation. 47

Fig 2.15: Degranulation of Mast cell.
• Serotonin: it is a performed mediator with vasoactive roles which

is released during platelet aggregation by platelet dense body
granules. It plays similar roles than histamine but is less potent.
• Cytokines: Activated monocytes and lymphocytes release a

variety of polypeptide substances called cytokines. The important
cytokines in acute inflammation include Tumor Necrosis Factor
(TNF) and Interleukin-1(IL-1) and in chronic inflammation-
Interferon-γ (IFN-γ).
The production of TNF and IL-1 is stimulated in response to

immune complexes, bacterial endotoxins and products of T
lymphocytes.
They are mainly responsible for endothelial activation.
• Chemokines: Molecules that serve as chemo-attractants for

leucocytes and activate them.
2. Plasma Derived Inflammation Mediators
It includes molecules from three systems, namely- fibrinolytic system,

clotting system and the complement. It involves inactive protein
molecules that are enzymatically activated by enzymes at the site of
inflammation.
• Hageman Factor: it is a plasma protein synthesized in the liver

that serves as the factor that activates all the three systems.
SAQ 5
Fill in the blanks:
i) .……………………… is main cell involved in acute inflammation.
ii) The main cells involved in chronic inflammation are ……………………,

……………………… and ……………………… is secreted by mast cells,
basophils and platelets and causes increased vascular permeability and
arteriolar dilation.
48
2.7 SUMMARY
Let us summarise what you have learnt in this unit:
• The innate immunity is the first, non-specific line of defence of the body
present from the time of birth whose components are present before the
initiation of infection.
• The innate immunity has physical, physiological, phagocytic and

inflammation barriers.
• Pattern recognition receptors recognise pathogen associated molecular

patterns on pathogens for example- Scavenger receptors.
• Toll like receptors initiate innate immune response by recognising

patterns on pathogens.
• NK cells are granular lymphocytes with cytotoxic activity even without

prior antigen priming. They have role in killing virus, cancerous cells and
in graft rejection.
• Complement system includes circulating serum proteins that are a part

of immune system that helps antibodies and other cells to kill the
pathogen.
• There are three pathways of complement activation- Classical,

Alternative and Lectin pathway. All these pathways are activated
differently.
• The Classical pathway of the complement system is activated by the

formation of an antigen-antibody complex.
• The Lectin and Alternative pathways are activated by binding of

antigenic molecules on pathogen to complement proteins. They do not
require the formation of an antigen-antibody complex.
• All the pathways lead eventually to the formation of a Membrane Attack

Complex (MAC) that lyses cells by inserting in the plasma membrane of
pathogen.
• There are several functions of the complement system like lysis of

pathogens, opsonisation, promotion of inflammation and also helps in
clearing immune complexes.
• Phagocytosis is a type of endocytosis performed by Antigen Presenting

Cells (APCs) through which the pathogen is engulfed.
• Inflammation is a cascade of events triggered due to wound/tissue

damage/pathogen invasion. It involves cells, blood vessels and various
molecular mediators.
• There are cell derived (e.g.-histamine) and plasma derived mediators

(e.g.- Hageman Factor) of inflammation.
• Localised and systemic effects are seen in acute inflammation. 49

• In allergies, transplants, autoimmune diseases, a chronic inflammatory
response is seen.
• Several inflammatory mediators are released due to degranulation of

mast cells and activation of macrophages.

a) ……………… and ……………… are the layers of the skin.
b) The pH of sebum is ……………… which is inhibitory to pathogens.
c) ……………… protects chickens from anthrax.
d) ……………… enzyme is in found in tears and saliva and is

bacteriolytic.
e) ……………… molecules create an antiviral state.
2. List the three parts of Toll like Receptors.
a) PAMPs
b) PRRs
c) DAMPs
d) MBL
4. Identify the following diagrams:
Sr. No. Diagram Identified as
1.
2.
3.
5. List the various steps of inflammation.

50
6. Explain the mechanism of activation of the Lectin pathway of
complement system.
7. Define the following terms:
i) Diapedesis
ii) Margination
iii) Chemotaxis
8. List the various signs of inflammation.
9. Identify the cell given below and write the significance of the granules
present.
2.9 ANSWERS
1. a) Mucosa
b) Lysozyme
c) Anatomical and physiological
d) Low pH
e) Peptidoglycan
2. a) i) False – can be nucleic acid, sugars also

ii) False, nucleic acid can also be a PAMP
iii) True
b) a) iii, b) i, c) ii.
3. i) True, ii) False, causes ion loss, ii) True.
4. a) Paul Ehrlich, b) Factor B, c) C1q, C1r, C1s, d) Mannose

Binding Lectin.
5. i) Neutrophil
ii) Macrophage, lymphocyte and plasma cells
iii) Histamine
Terminal Questions
1. a) Dermis and Epidermis, b) 3-5 pH, c) High body temperature,
d) Lysozyme, e) Interferons. 51
2. The three parts of Toll like Receptors are:
i) LRRs -leucine-rich repeats motif. It helps in the recognition of

pathogen.
ii) A trans membrane domain.
iii) Cytoplasmic Toll/IL-1 receptor (TIR) domain- It initiates signalling

by interacting with signal transduction adaptors.
3. i) Pathogen Associated Molecular Patterns.
ii) Pattern Recognition Receptors.
iii) Damage Associated Molecular Patterns.
4. Identify the following diagrams:
Sr. Diagram Identified as

No
1. Phagocytosis by
macrophage
2. Phagosome
3. Membrane
attack complex
5. The various steps of inflammation are:
i) Vasodilation
ii) Increase in capillary permeability
6. The Lectin pathway does not need the formation of antigen-antibody

complex for its activation. Pathogens like Salmonella, Candida albicans,
Listeria have mannose residues on the carbohydrates or glycoproteins
present on their surface. These mannose residues bind to mannose-
binding lectin (MBL) and thus lead
lead to the activation of the Lectin
pathway.
7. i) Margination- adherence of cell to endothelial wall of blood vessels.
ii) Diapedesis/Extravasation- Phagocytes migrate between capillary

endothelial cell and into tissues.
iii) Chemotaxis- Migration through tissue to site of invasion.
8. The various signs of inflammation are:
i) Rubor- redness
52
ii) Calor- heat
iii) Tumor- swelling
iv) Dolor-pain
v) Galen- loss of function.
9. The cell is a Natural Killer (NK cell). The granules denote perforin and
granzymes that help the NK cell to lyse the target cell. When such
molecules are realeased in proximity to the infected cell, perforins create
pores in the plasma membrane and allow entry of granzymes and other
enzymes, thus the cell undergoes apoptosis.
53
Block-1 Introduction to Immunology
UNIT 3
COMPONENTS OF IMMUNE
SYSTEM
SYSTEMII
Structure
3.1. Introduction 3.8. Primary and Secondary
Objectives
Immune Response
3.2. Adaptive Immunity Primary Immune Response
Four Characteristics of Adaptive The Secondary Immune

Immunity Response Response
3.3. B Lymphocytes 3.9. How do the Innate and

Adaptive Immune Systems
3.4. T Lymphocytes Work Together?
3.5. Cytokines
Natural Killer Cells-The Bridge
Different Features of Cytokines between Innate and Adaptive
Nomenclature of Cytokines Immune Systems
Functions of some Cytokines 3.10. Acquired Immunity
Chemokines Naturally Acquired Immunity
3.6. Humoral Immunity Artificially Acquired Immunity

Antibodies 3.11. Summary
Steps of Humoral Immunity 3.12. Terminal Questions
3.7. Cell Mediated Immune 3.13. Answers
Response (CMI)
3.1 INTRODUCTION
This unit aims to provide basic concept to the adaptive immune system of the
body. The adaptive or acquired immune system comes into action once the
pathogen has breached the innate immune system. The innate immune
system passes on stimulatory signals to activate the adaptive immunity. We
would study about various cells and molecules involved in the adaptive
immunity response. B cells on activation produce plasma cells that secrete
antibodies and generate memory cells that are dormant cells which are
activated on subsequent pathogen exposure. The T cells go on to produce
54 cytotoxic T lymphocytes that are involved in direct killing of the pathogen.
Unit 3 Components of the Immune System-II
An overview of the humoral and cell mediated immune systems is also
provided. The humoral immune response involves various components in the
body fluids like antibodies, complements and antimicrobial peptides; while the
cell mediated immune system has cell components to neutralize the pathogen.
We would also understand the difference between primary and secondary
immune responses. Then we would proceed to understand the
interrelationship between the innate and adaptive immune systems via NK
cells.
Objectives
 gain an insight about the adaptive immune system,
 differentiate between naturally and artificially acquired immunity,
 list the various features of adaptive immunity,
 explain B and T lymphocytes,
 discuss the role of cytokines and chemokines,
 give examples of cytokines with their functions,
 differentiate between humoral and cell-mediated immunity,
 list the steps of antibody activation,
 list the features of primary and secondary response, and
 explain the role of NK cells as a bridge between innate and adaptive

immune systems.
3.2 ADAPTIVE IMMUNITY

Foreign pathogens and antigens are selectively recognised and eliminated by
the adaptive immune system when the innate immune system fails to defend
the body against the pathogen invasion. However, it is capable of responding
only when a stimulus is provided by the innate immune system.
The Adaptive or Acquired immune response takes much longer time than the
innate immune response to become activated and respond. It can take days or
even weeks but adaptive immunity is more pathogen specific and also has
memory. Adaptive immune response is generated post exposure to a
pathogenic antigen or after a vaccination. The responses are tailor made to
challenge specific antigen unlike the innate immune system.
The differences between innate and adaptive immunity are given in Table 3.1. 55
Table 3.1: Differences between innate and adaptive immunity.
Lines of Timeline Cells Antigen Example

defense dependenc
y
Innate First Immediate NK cells, Independent Skin, hair,

(Non- response macrophages, cough,
specific) (0-96 neutrophils, mucous
hours) dendritic cells, membranes
mast cells, phagocytes,
basophils, granulocytes.
eosinophils.
Adaptive Second Long term T and B Dependent Pus,

(Specific) (>96 lymphocytes swelling,
hours) redness,
pain.
3.2.1 Four Characteristics of Adaptive Immune

Response
Adaptive immune responses are carried out by white blood cells called
lymphocytes. Four major features of adaptive immune response are as
follows:
i) Antigen specificity: This allows the immune system to detect even

minor differences among antigens. Antibodies can recognize even single
amino acid differences among protein molecules.
ii) Diversity: The property of adaptive immune system to generate

enormous diversity in the recognition molecules allows it to identify
billions of molecules on foreign antigens and pathogens.
iii) Immunologic memory: This attribute of generating memory against

specific antigen/ pathogen post primary encounter with the antigen
allows providing up to life long immunity to various pathogens due to
formation of memory B and T cells after initial exposure.
iv) Distinction between self and non-self: It is critical that the immune
system reacts and responds not only to non-self-molecules as response
to self-molecules can lead to several fatal conditions like autoimmune
disorders.
There are two types of adaptive immunity namely
a) Humoral Immune Response (Antibody Response) mainly involves B

cells and antibodies.
b) Cell mediated Response mainly involves T cells.
Before studying Humoral Immune Response and cell mediated response in

this unit let us discuss about B and T lymphocytes, cytokines and chemokines
56 in the following section.
3.3 B LYMPHOCYTES
They are lymphocytes that are named so due to their occurrence from the site
Bursa of Fabricius: is
of maturation in birds called the Bursa of Fabricius. In mammals like mice and a chestnut size sac
humans, B lymphocyte maturation occurs in the bone marrow. They are like lymphoid organ in
distinct from other lymphocytes and cells in the respect that they display birds,located dorsal to
membrane bound antibody molecules. These antibody molecules have the the rectum, anterior to
same antigen specificity and antigen binding sites. the sacrum,
communicating with
Several other molecules are found on the B-cell surface (Table 3.2) the posterior portion
of the cloaca. In birds
Table 3.2: Molecules expressed on B cell surface. B cells mature here.
Sr. Molecule Role

No expressed
1. B220 Frequently used as marker for precursor B cells

and mature B cells.
2. CR1 and CR2 They are receptors for the complement products
to bind.
3. CD32 Receptor for IgG
4. MHC Class II They allow B-cells to act as Antigen Presenting

molecule Cells
5. CD 40 Interacts with the CD40 on helper T cell surface.
The interaction of naive B cells antibodies with antigen, as well as with

macrophages and T-cells, causes rapid proliferation of B cells leading to the
production of B-cell clones. These cells differentiate into memory B cells and
plasma cells (Fig 3.1). The plasma cells rapidly secrete antibodies while
the memory cells act on subsequent exposure with the antigen.
Fig 3.1: Differentiation of B lymphocyte in plasma cells and memory B cell. 57

3.4 T LYMPHOCYTES
T lymphocytes are cells that mature in the thymus. They have T Cell
Receptors (TCRs) that are membrane bound receptors that do not directly
recognise the antigen. Most T-cells can recognise antigens only when they are
coupled with Major Histocompatibility molecule found on antigen presenting
cells like macrophages and dendritic cells and on tumor cells.
Several molecules are displayed on the membrane of T cells.
1. T-cell Receptor (TCR)

2. CD45 and CD28.
Two distinct subpopulations of T cells can be distinguished based on the
expression of CD4 and CD8 molecules:
1. CD4+ cells: They can recognise antigen bound to class II MHC
molecules and usually function as helper T cells (TH). Activity of TH cells
is depicted in Fig 3.2.
2. CD8+ cells: They recognise antigen bound to class I MHC molecules
and function as cytotoxic T cells (TC). Fig 3.3 depicts the activity of TC
cells.
Fig 3.2: Flowchart depicting the activity of helper T-cells (TH).
58 Fig 3.3: Flowchart depicting the activity of cytotoxic T-cells (TC).

3.5 CYTOKINES
Cytokines are group of proteins secreted by white blood cells and many
other cells of the body in response to external stimuli. They are low
molecular weight proteins or glycoproteins with regulatory roles.
Cytokines trigger signal transduction pathways and eventually lead to

alteration of gene expression in target cells by binding to specific
receptors located on the target cell. It is the presence of these receptors
that determines whether or not a cell is susceptible of action of a particular
cytokine molecule.
The cytokines may have:
Cytokines are involved in the stimulation or inhibiting the activation and

proliferation of many cells, regulation of antibody secretion and also the
secretion of other cytokines. In this way they are able to regulate the
magnitude and duration of the immune response.
The binding of cytokines to the target cells leads to increased expression of

cytokine receptors and also causes secretion of more cytokine molecules
which go on to affect other target cells. Therefore, even a small amount of
cytokines secreted by antigen activated lymphocytes can affect the activity of
many immune cells. For example, a plethora of interacting cells like B cells,
NK cells, macrophages, Tc cells, granulocytes and HSCs- (Hematopoietic
Stem Cells) are activated by the cytokines released by TH cells.
3.5.1 Different Features of Cytokines

Cytokines exhibit different features as discussed below:
1. Pleiotropy: It is the exhibition of different biological effects on different

target cells by the same cytokine. For example, IL-4 secreted by
activated TH cells goes on to activate B cell, thymocyte and mast cells.
2. Redundancy: It is when the same function is performed by two

cytokines. Thus, it becomes difficult to attribute a function to one
particular cytokine. For example, IL-2, IL4 and IL-5 secreted by activated
TH cells cause B cell proliferation. 59
3. Synergy: Synergy occurs when the additive function of two cytokines is
more than the function of a single cytokine.
4. Antagonism: The effect of one cytokine inhibits the function of other

cytokine.
5. Cascade induction: It is the initiation of a sequence of events where

the production of cytokine by a cell activates another cell. Now the
activated cell secretes more cytokines which further activate more target
cells.
3.5.2 Nomenclature of cytokines

Cytokines are principally named on the basis of the cells that produce them.
For example:
• Lymphokines: cytokines produced by lymphocytes.
• Monokines: cytokines produced by macrophages and monocytes.
• Interleukins: cytokines secreted by leukocytes and act on other

leukocytes.
• Some cytokines are also called by their common names. For example,
tumor necrosis factors.
3.5.3 Functions of some cytokines

Functions performed by some cytokines are as discussed below:
• TNF-α (tumor necrosis factor-α): It is synthesized by macrophages

and has several functions like: inflammation, formation of acute phase
proteins in liver, neutrophil activation and loss of body fat and muscle.
• Interferon-α: It is secreted by macrophages. It creates an antiviral state

in nucleated cells, activates NK cells and increases the expression of
MHC I expression.
• Interleukin -2: This is secreted by T-cells and causes B cell

proliferation, T cell proliferation and activation of NK cells.
• Interferon-γ: This is secreted by CD8+ T cells and NK cells. Serves to

activate macrophages, stimulates better antigen presentation and
increases the overall expression of MHC molecules.
3.5.4 Chemokines
Chemokines are cytokines that act as chemo-attractants. They play an
important role in migration of cells between blood and tissues through venules
during the process of chemotaxis. (Chemotaxis is the stimulation of cell
movement in response to chemical stimuli such as cytokine gradients).
Chemokines are also known to influence development of lymphoid organs and
T-cell differentiation. They mediate tumour cell metastasis and also function as
neuro-modulators in the nervous system.
Chemokine receptors are required for the action of chemokines on the target
cells. These receptors belong to G-protein coupled receptors (GPCRs) family
60 and help in initiating intracellular signalling pathways (Fig 3.4).
Fig 3.4: Mechanism of action of Chemokines
SAQ 1
State ‘True’ or ‘False’:
i) B lymphocyte maturation in mammals like mice and humans occurs in

the bone marrow.
ii) Redundancy is not a feature of cytokines.
iii) TCRs do not directly recognise antigens.
SAQ 2
Match the following items given in Column A with Column B.
Column A Column B
i) CD45 and CD 28 a) Macrophages
ii) Monokines b) Receptor for IgG
iii) B-cells c) Expressed on T-cells
iv) Interferons d) Bear antibody on surface
v) CD32 e) Antiviral state
61
3.6 HUMORAL IMMUNITY
Humoral immunity depends on molecules found in the “humor”, that is the
body fluids. It is mediated by molecules like antibodies, various complement
proteins and antimicrobial peptides. Therefore, it is also as Antibody
Mediated Immunity.
Humoral immunity involves the production of antibodies and simultaneous

occurring of events like the activation of helper T-cells and production of
cytokines. It is also involved in various effector functions of antibodies like:
• Classical pathway of complement activation
• Opsonisation of pathogen and help in phagocytosis.
3.6.1 Antibodies
Antibodies are immunoglobulins found in blood, tissue fluids and various
secretions of the body. They are globular proteins that are synthesized and
produced by plasma cells that are formed by activated B-cells. Five different
classes of antibodies are found in the body. They are: IgG, IgM, IgA, IgE and
IgD. You will study about them in detail in Unit 7 of this course.
Antibodies are used by the adaptive immune system to neutralize various

pathogens like viruses and bacteria. The antibodies can bind to specific
targets and cause agglutination and precipitation reactions. As a result various
immune complexes are formed that can be cleared from the body. Antibodies
also promote phagocytosis by various cells like macrophages and activate the
complement system.
3.6.2 Steps of Humoral Immunity

Various steps of humoral immunity are discussed below and shown in Fig 3.5.
1. Production of B-cells: The production of B cells occurs in bone

marrow. They have B-cell receptors (BCRs) displayed on their surfaces
which are specific for particular antigens. These mature B-cells that go
on to encounter pathogens in lymphoid organs, to where they have
migrated.
2. The activation of B-cells: The mature B cell encounters antigen in the

lymphoid organs. The antigen binds to the BCR which is then
internalised by endocytosis. The antigen fragments are then presented
with MHC-II molecules.
3. The proliferation of B-cells: The helper T-cell get activated on binding

to B-cell. The activation of helper T-cells results in release of various
cytokines that go on further to activate the B-cells to proliferate rapidly.
Soon a clone of B-cells is formed and these cells eventually form
memory cells or plasma cells. The plasma cells secrete large amounts of
antibodies while the memory cells are in a temporary resting state which
62 gets activated on subsequent encounter with the pathogen.
4. Antigen –antibody reaction: The antigen and antibody then react
forming an immune complex which is cleared from the body.
Fig 3.5: The steps of Humoral Immune Response.
3.7 CELL MEDIATED IMMUNE RESPONSE (CMI)

The cell mediated immune response is the method of the body to fight against
pathogens like bacteria and viruses. It is also responsible for the killing of
cancerous cells and in the graft-rejection process.
The foreign antigen is recognised by macrophages and dendritic cells of the

innate immune system. They internalise the pathogen, degrade it and present
their antigenic peptides on their surface with class II MHC molecules. This
MHC-antigenic complex is responsible for the activation of adaptive immune
system.
CD4+ and CD8+ T cells are formed from T-cell precursors in the thymus. The
MHC Class II complex on APCs interact with the CD4+ T cells while the
CD8+ T cells interact with the antigen- Class I MHC complex found on infected
or cancerous cells. The CD8+ T cells transform into Cytotoxic T lymphocytes
(CTL) and are responsible for the destruction of the infected or the cancerous
cell. (Fig 3.6)
The CD4+ cells prior to the interaction with MHCII- antigen complex present on
APCs are called as naive cells. The naive cell on activation can form memory
T cell or other TH-cell variants-
• Interferons are produced by Type I helper T-cells that cause pathogen

digestion with the APCs. They also stimulate CTL and B-cell activity.
• Interleukins that promote B cell activity are produced by Type II helper T-

cells. 63
Fig 3.6: Mode of action of Cell-Mediated Immunity.
You have studied about humoral and cell mediated immunity. In Table 3.2
differences between the two types of immunity are listed.
Table 3.2: Differences in Humoral and Cell mediated Immunity.
Sr. Humoral Immunity Cell-mediated Immunity

No.
1. The response is mediated by The response is mediated by cells.

antibodies.
2. Only helper T cells are involved. Both CD4+ and CD8+ T cells are
involved.
3. Mediated by B cells, T cells and Mediated by helper T-cells, cytotoxic

macrophages. T cells, NK cells and macrophages.
4. Involves B-cell receptors. Involves T-cell receptors.
5. Participates in homografts The preformed antibodies may lead

rejections and in GVHD- Graft to early graft rejection.
versus host disease.
6. No role in immune surveillance. Has role in defense against cancer

cells and also in immune surveillance.
SAQ 3
Fill in the blanks with appropriate words:
i) CD4+ and CD8+ T cells are formed from …………………... in the thymus.
ii) The CD8+ T cell transforms into .......................... that are responsible for
the destruction of the infected or the cancerous cell.
iii) …………………… participates in homografts rejections and in GVHD-

Graft versus host disease.
64
3.8 PRIMARY AND SECONDARY IMMUNE
RESPONSES
3.8.1 Primary Immune Response
Primary humoral response is generated when primary contact with the
exogenous antigen is established. It leads to the production of plasma cells
that secrete large amounts of antibodies and memory B cells.
The magnitude and kinetics of primary humoral response depend on several

factors like:
• Nature and type of antigen.
• The involvement of adjuvants.
• Route of antigen administration.
• The species of the organism.
The primary response has a long lag period during which several activities
occur like; clonal selection of B cells, their clonal expansion and subsequent
differentiation into plasma cells or memory cells. An exponential increase in
the serum antibody level is seen after the log phase. A plateau is reached after
some time and then the antibody levels gradually decline.
The process of antibody production has four distinct stages as discussed

below and shown in Fig 3.7.
1. Lag phase: It is the phase when primary contact with the antigen is
established. IgM appears and engages the antigenic element. The
length of the lag phase is variable. For example- the pneumococcal
polysaccharide persists for several hours while the Diphtherial toxin lasts
for 2-3 weeks.
2. Log phase: Rapid increase in the antibody levels.
3. Plateau: An equilibrium state where the antibody production and decay

is balanced.
4. Decline phase: The antigenic stimulus is removed and the serum

antibody level begins to fall.
Ab Titre
Time
Fig. 3.7: Stages of antibody production. 65

Initially a rise in the serum IgM levels is seen and later it is replaced by IgG
antibody. The IgM has higher avidity, which means that it is capable of
engaging more diverse antigens. The IgG on the other hand is more specific to
a particular antigen and thus appears in later stages of the immune response.
The primary response can last from a few days to a several weeks depending
on the antigen and the severity of the infection.
The memory cells that are generated during this process move out of the cell
cycle and progress into the Gο phase, where the cell is less metabolically
active. These memory cells last for variable durations in the body and some
may last for even the entire lifetime. It is the population of memory T cells and
memory B cells that together elicit the secondary immune response on
subsequent encounter with the same antigen.
3.8.2 The Secondary Immune Response

The secondary immune response is generated on subsequent exposure to the
antigen and its interaction with memory B cells generated during the primary
response. In secondary response, the lag phase is shorter but the magnitude
is greater and persists longer. There is secretion of antibodies other than IgM
that are more specific to the antigen.
Reasons for rapid and higher magnitude response in Secondary

Response
1. The population of naive B-cells is much lower that the more antigen
specific memory B cells.
2. The memory B cells are more readily activated than naive B-cells.
The production of higher affinity and different antibodies other than IgM is due
to the processes of:
1. Affinity maturation
2. Class switching.
Therefore, the antibodies produced are equipped with better effector functions
that are customised for a particular pathogen. There is a 100-1000 fold
increase in antibody concentration as compared to primary response and the
predominant antibody in this case is IgG along with IgA and IgE. In Table 3.3
Primary and Secondary Responses are compared and comparison of Ig levels
in serum in both the responses is depicted in Fig. 3.8.
Table 3.3: Differences between Primary and Secondary Immune

Responses.
Sr. Primary Response Secondary Response

No.
1. Occurs following first It occurs on encountering the same

exposure to a foreign antigen subsequently.
antigen.
66
2. A longer lag phase is The lag phase is very short.
observed that may last from a
few days to a few weeks.
3. Weaker response. Effective, rapid and more specific

response.
4. Appears mainly in spleen and First seen in bone marrow, then in

lymph nodes. lymph nodes and spleen.
5. IgM antibody predominates. IgG antibody predominates, also

small amounts of IgM, IgA, IgE.
(Fig 3.8)
6. The response occurs by Response occurs by memory B

naïve B cells and naïve T and T cells.
cells.
7. Rapid decline in antibody Antibodies persist for longer time.

levels is seen and become
undetectable after some time.
Fig 3.8: Comparison of serum Ig levels in primary and secondary immune

response.
3.9 HOW DO THE INNATE AND ADAPTIVE

IMMUNE SYSTEMS WORK TOGETHER?
As seen earlier, foreign pathogens and antigens are selectively recognised
and eliminated by the adaptive immune system when the innate immune
system fails to defend the body against the pathogen invasion. It is capable of
responding only when a stimulus is provided by the innate immune system.
An antigen is a non-self or foreign molecule that is recognised by cells of the

innate immune system. The information is then passed on to the adaptive
immune system. These cells are called antigen-presenting cells (APC) and
they recognise, engulf and pass on the activation signal to the adaptive
system. 67
The pathogen/antigen is phagocytosed by APCs and then digested into many
smaller fragments. These antigenic fragments are then transferred to the
surface of the APC. This fragment will act as a signal for other immune cells
activation. Dendritic cells and macrophages act as professional antigen
presenting cells.
Once the antigen is phagocytosed, a phagosome is formed which then fuses

with a lysosome to form a phagolysosome where the antigen is broken down,
and then attached to class II MHC molecules. The class II MHC molecules-
antigen peptide complex is then moved to the cell surface and present the
antigen peptides. Various immune cells respond when antigen is presented by
MHC-II molecules. One of the main cells to respond is Helper T-cells. They
release cytokines and cause further activation of cells.
Additionally, the adaptive immunity is fully activated by danger signals

displayed on cells. This occurs when the Pattern Recognition Receptors
(PRRs) present on APCs like macrophages and dendritic cells recognise
general classes of molecules frequently displayed by pathogens but never our
own body. These pathogen specific patterns are called Pathogen Associated
Molecular Patterns (PAMPs). This triggers events in the cell due to which
threat signals are displayed by cells. Also, various cytokines, chemokines and
chemotactic lipids are released that bring the adaptive immune system into
action. Furthermore, dendritic cells bridges the innate and adaptive immune
systems by presenting antigen and communicating the signal of activation to
CD4+ Helper T lymphocytes.
3.9.1 Natural Killer Cells-The Bridge between Innate and

Adaptive Immune Systems
The functional borders between innate and adaptive immune system is blurred
due to the sophisticated biological roles played by NK cells.
The immune system has been divided into: Innate immunity and Adaptive
immunity. The innate immunity consists of myeloid and lymphoid cells having
limited number of germ line-encoded receptors which cause rapid effector
functions. The adaptive immune system consists of lymphocytes- the B and T
cells that express a wide variety of antigen receptors. The receptors of these
cells are produced by site-specific somatic recombination. Naive B and T cells
exert their effector functions after undergoing cell division and maturation on
encountering the antigen in lymphoid organs.
NK cells are a population of white blood cells that have been classified as
lymphoid cells as:
• They originate from the common lymphoid progenitor cells.

• Many lymphoid markers are expressed by them.
• Morphological similarity.
NK cells do not express antigen specific receptors on their surface and are
thus considered to be a part of the innate immune system. They are cytolytic
cells that can kill tumor cells or virus infected cells even in the absence of any
68 prior immunisation, unlike cytotoxic T-cells.
NK cells are also known to produce many cytokines, chemokines and growth
factors. In several pathological and physiological conditions, several cytokines
like Interferon –γ (IFN-γ), pro-inflammatory cytokines like Tumor necrosis
factor-α (TNF-α) and immunosuppressive cytokines like interleukin (IL–10) are
also secreted. The NK cells are able to influence T-cell responses through the
secretion of interferon –γ. There is a direct interaction between naive T cells
and NK cells migrating from the site of inflammation in peripheral tissues to
secondary lymphoid compartments. Growth factors like G-CSF (granulocyte
colony-stimulating factor), IL-3 and as GM-CSF (granulocyte macrophage
colony-stimulating factor) are also produced. The chemokine molecules
secreted include CCL2, CCL3, CCL4, CCL5 and CCL8. These chemokines
play important role in facilitating the presence of NK cells with dendritic cells at
the site of inflammation.
The T cell responses are influenced by the killing of target cells by NK cells by
probably-
• Decreasing the load of antigen.

• Cross presentation of target cell debris to CD8+ cytotoxic T cells.
It is established that NK cells have cytolytic effects against tumor cells or virus
infected cells, but they also impact dendritic cells, macrophages and
neutrophils due to cytokine production and cytotoxicity. Thus NK cells play an
important role in influencing subsequent interaction of B and T cells with
antigens. Depending upon the nature of antigen, NK cells can negatively or
positively influence the B and T cell of the host immunity through the secretion
of IFN-γ and IL-10.
SAQ 4
Do as directed:
i) ………………... have cytolytic effects against tumor cells or virus
infected cells. (Fill the blank)
ii) Initially a rise in the serum IgM levels is seen in primary immunity and
later it is replaced by IgG antibody. (True/False)
iii) IgM has more affinity than IgG. (True/False)
3.10 ACQUIRED IMMUNITY

There are two types of acquired immunity viz. naturally acquired and artificially
acquired immunity (Table 3.4)
Table 3.4: Differences between Naturally Acquired and Artificially

Acquired Immunity.
Sr. Naturally Acquired Immunity Artificially Acquired Immunity

No
1. Active- This is acquired when Active- Killed or attenuated

the antigen enters the body pathogen is introduced in the host.
naturally; the host fights it and This process is called vaccination.
recovers naturally.
69
2. Passive- It occurs when the Passive- Preformed antibodies are
antibodies are passed from given to individual from an immune
mother to the foetus through animal/person.
the placenta or when the
antibodies are given to child
via breast milk.
3.10.1 Naturally Acquired Immunity

Naturally acquired immunity can be divided as active or passive-
1. Active: When a pathogen enters the body, the innate immune system
passes on a message for the activation of adaptive immune system via
antigen presenting cells. The B and T cells are activated via interaction
between cells and the secretion of many cytokines, chemokines and
other molecules. Eventually, memory B and T cells are formed and
immunologic memory of the antigen/pathogen is retained in the body.
Also, receptors specific to the pathogen are acquired by the host. On
subsequent exposure to the same pathogen, a much exaggerated
secondary response is mounted. This also forms the basis for
vaccination.
A wild infection with for example Hepatitis A virus would elicit an immune
response. A lifelong protection can be generated post- recovery.
2. Passive: New-borns are particularly susceptible to infections as they

have no prior exposure to most antigen/pathogens. Thus, the mother
provides passive protection to the baby.
The maternal antibodies (MatAb) are transferred from mother to the

foetus through the placenta via FcRn receptor found on placental cells.
This happens around the end of first trimester. Thus very high antibody
levels are found in the baby at the time of birth. These antibodies have
almost the same specificity for antigen as the mother. The only
antibody that can cross the placenta is IgG.
Also, breast milk contains large amounts of secreted antibodies (mainly

IgA) that protect the new-born till it becomes capable of synthesizing
antibodies itself.
This immunity is however very short lived as no antibodies are

synthesized or immunological memory is generated.
3.10.2 Artificially Acquired Immunity

The Artificially acquired immunity can be active or passive.
1. Active: This can be acquired by the process of Vaccination. A vaccine

contains an antigenic substance that can induce primary immune
response without producing any signs or symptoms of the disease. The
term “vaccine” was adopted by Louis Pasteur in honour of Edward
70 Jenner who developed the small pox vaccine in 1796.
The vaccination process involves providing immunization by priming the
immune system with the antigen deliberately. There are several types of
vaccines- their types and example are given in Table 3.5.
Table 3.5: Different types of vaccines and their examples.
Sr. Vaccine Description Examples

No
1. Inactivated Composed of potentially pathogenic Cholera
vaccines microorganisms that are no longer Flu
capable of causing infection as they
Plague
have been killed using chemicals/ heat
or other treatments.
2. Attenuated The potentially pathogenic Mumps
vaccines microorganisms are inactivated/ Rubella virus
weakened and are no longer capable of
Yellow fever
causing infection.
3. Toxoid based Used when the disease is caused by Tetanus

vaccines pathogenic toxin rather than the
pathogen itself.
4. Subunit/ Immunisation with small pathogenic Hepatitis B
recombinant fragments. virus
vaccine
2. Passive: Passive immunisation is critical when the infection is rapidly

spreading and there is insufficient time for the body to develop response
and protect itself. Artificially acquired passive immunity is due to the
intravenous or intramuscular injection of preformed antibodies from
human or animal plasma through antiserum therapy and immunoglobulin
therapy. This is short lived as no response is generated and antibodies
are superficially administered. It used in the treatment of several
types of acute infections and in the treatment of poisoning.
However, in this method the major drawback is the risk of developing

hypersensitivity reactions, especially when gamma globulins are
involved from non-human sources.
SAQ 5
Fill in the blanks:
i) A vaccine contains an ………………… that can induce primary immune

response without producing any signs or symptoms of the disease.
ii) The only antibody that can cross the placenta is ……………………...…. .
iii) During primary contact with the antigen, memory of this encounter is
generated in our system in the form of ……………………........ .
iv) In …………………… vaccine the potentially pathogenic microorganisms

are inactivated/weakened and are no longer capable of causing
infection.
71
3.11 SUMMARY
Let us summarise whatever you have learnt in this unit
• Adaptive immune response is generated post exposure to a pathogenic

antigen or after a vaccination. The responses are tailor made to specific
antigenic challenges and not present naturally like the innate immune
system.
• The features of adaptive immunity are diversity, antigen specificity,

immunologic memory and self and non-self-differentiation.
• The acquired immunity can be naturally and artificially acquired.
• There are several types of vaccines:-inactivated, attenuated, toxoid and

recombinant vaccines.
• B-cells are formed in the bone marrow and on activation form memory
and plasma cells.
• A signal transduction pathway is initiated by BCR binding to antigen.

This leads to the activation of B-cells.
• T-cells that recognise antigen-MHCII molecule function as helper T-cells.
• T-cells that recognise antigen-MHCI molecule function as cytotoxic T-

cells that on activation form cytotoxic T-lymphocytes.
• Cytokines are low molecular weight proteins or glycoproteins with

regulatory roles.
• Cytokines trigger signal transduction pathways and eventually lead to

alteration of gene expression in target cells by binding to specific
receptors located on the target cell.
• Cytokines exhibits several features: redundancy, pleiotropy, synergy and

antagonism.
• Humoral immunity is mediated by molecules like antibodies, various

complement proteins and antimicrobial peptides. Therefore, it is also
known as Antibody Mediated Immunity.
• The cell mediated immune response is the method of the body to fight
against pathogens like bacteria and viruses. It is also responsible for the
killing of cancerous cells and in the graft-rejection process.
• Primary response is seen on first encounter with the pathogen. It usually

has a long lag phase. IgM is the main antibody involved.
• Secondary response is seen on subsequent exposure to the same

72 antigen. It has a much shorter lag phase and is of a greater magnitude.
a) CTL
b) MHC
c) TH cell
d) APC
Attenuated vaccine Cholera
Toxoid Mumps
Killed vaccine Tetanus
3. State as ‘True’ or ‘False’.
i). Interleukin -10 is a cytokine.
ii). NK cells need prior antigen exposure to get activated and cause
cytolytic activity.
iii).The memory B-cells are more easily activated than naive B-cells.
4. List the various factors that determine the kinetics of humoral response.
i). …………………… is an example of active artificially acquired

immunity.
ii). …………………… is an example of active naturally acquired

immunity.
iii).Passage of antibodies via mother’s milk is an example of

...…………….
6. Why is the IgM that appears early in the infection replaced by IgG
antibodies in the later exposure?
7. Label the stages of antibody production given in the figure.
73
i) Activated B cell clones form …………......… and ………………….

cells.
ii) B-cells are called so due to their origin in ……………………. in

birds.
iii) CD8+ T cell activated transform into …………………… .
iv) B-cells mature in …………………… lymphoid organ.
9. Provide a name for the following situations.
i) IL-4 secreted by activated TH cells goes on to activate B cell,

thymocyte and mast cells.
ii) IL-2, IL4 and IL-5 secreted by activated TH cells all cause B cell
proliferation.
3.12 ANSWERS
1. i) True, ii) False, iii) True.
2. i) c, ii) a, iii) d, iv) e, v) b.
3. i) T-cell precursors
ii) Cytotoxic T-lymphocyte
iii) Humoral immunity
4. i) NK cells, ii) True, iii) False, iv) True.
5. i) Antigenic substance.
ii) IgG.
iii) Memory B and T cells.
iv) Attenuated vaccine.
Terminal Questions
1. a) Cytotoxic T lymphocyte.
b) Major Histocompatibility Complex.
c) Helper T cell.
d) Antigen presenting cell.
Attenuated vaccine Mumps
Toxoid Tetanus
Killed vaccine Cholera

74
3. i) True, ii) False, iii) True.
4. Factors that determine the kinetics of humoral response are:
• Classical pathway of complement activation.
• Opsonisation of pathogen and help in phagocytosis.
5. i) Vaccination.
ii) Exposure to antigen and natural recovery of the body.
iii) Passive naturally acquired immunity.
6. Initially a rise in the serum IgM levels is seen and later it is replaced by
IgG antibody. IgM has higher avidity, which means that it is capable of
engaging more diverse antigens. The IgG on the other hand is more
specific to a particular antigen and thus appears in later stages of the
immune response.
7.
8. i) Memory cells and plasma cells.
ii) Bursa of Fabricius.
iii) Cytotoxic T lymphocytes.
iv) Bone marrow.
9. i) Pleiotropy, ii) Redundancy.
75
UNIT 4
ORGANS OF IMMUNE SYSTEM
Structure
4.1 Introduction 4.5 Summary
Objectives 4.6 Terminal Questions
4.2 Lymphoid Organs 4.7 Answers
4.3 Primary Lymphoid Organs
4.4 Secondary Lymphoid Organs
4.1 INTRODUCTION
In the previous units you have studied about various important components of
immune system. You have also learnt about their significant role in providing
immunity. Human immune system is made up of many different organs and
tissues that are present throughout our body.
In this unit you will be studying about organs of immune system. These organs
broadly divided into two types that is primary lymphoid organs and secondary
lymphoid organs. However, in your previous courses you might have learnt
about these organs and their physiological importance. These organs are
located at different parts of your body and also have differences in their
activities. Primary lymphoid organs responsible for the development of
immune cells whereas secondary lymphoid organs act as site of immune
response.
In simple words primary lymphoid organs acts as sites where production of

lymphoid cells takes place and secondary lymphoid organs are the battle
grounds where antigen and antibody interaction takes place. You would be
excited to know the significant role played by bone marrow and thymus in
developing the immune cells. While studying this unit you will come across
lymphatic nodes and their significance as secondary lymphoid organs in
responding and providing immune response against the antigens.
In this context this unit is acting as a connecting link between the various
components of immune system and immunogenicity that is exhibited by
76 immune system.
Unit 4 Organs of Immune System
Objectives
After studying this unit you should be able to
 identify the important organs of immune system,
 compare and differentiate functions executed by primary and

secondary lymphoid organs,
 explain the involvement of lymphoid organs at various stages of

immune response, and
 enlist the biological significance exhibited by lymphoid organs.
4.2 LYMPHOID ORGANS

In BZYCT-135, you have studied about different organs of our body and there
diverse functions. During this you might have noticed that these organs have
different structures and functions and also located throughout the body. The
coordination among these organs is very much essential for the maintenance
of health. Similarly, there are different its lymphoid organs exist in our body
and are performing various functions in the development of immunity or
immune responses (Fig 4.1).
Fig. 4.1: Lymphoid Organs.
These organs can be e classified into two major groups that is as primary and
secondary lymphoid organs. To know more about role of lymphatic system in
immunity you are advised to watch the video available at the following link
https://youtu.be/kjLwVqxwaIM. 77
4.3 PRIMARY LYMPHOID ORGANS
We all know that B- Both thymus and bone marrow are considered as central or primary lymphoid
cells play an organs. These are the sites of lymphocyte maturation. In brief the immature
important role in the
lymphocytes produced during haematopoiesis get mature towards specific
immune system by
producing antibodies antigen inside these primary lymphoid organs. During this maturation process
whereas T-cells have lymphocytes attain the property of 'immunocompetent' i.e., the ability to show
a specific role in immune response.
performing cell
mediated immunity You are aware that there are two major types of immune cells like T cells and
which is significant B cells. Thymus is the site where T cells arise, however bone marrow is the
with respect to
site for the origin of B cells. Let us discuss about these two significant primary
controlling viral
infections. It is well
lymphoid organs in the following sections.
established that
THYMUS
antibodies are
clinically essential It is located above the heart; it has a flat, bilobed structure (Fig 4.2). These
to fight against covid-
lobes are surrounded by capsule like structure and are separated from each
19 infection. However
specific antibodies other by a connective tissue strands called as trabeculae. Each lobule is
levels against severe divided into two compartments the outer compartment is known as cortex
acute respiratory which is densely packed with immature T cells that are known as thymocytes.
syndrome corona However, the second inner compartment which is known as medulla contains
virus (SARS-CoV-2)
few thymocytes.
dropped below the
limit of detection
within 2-3 years,
whereas the specific
memory T-cells have
been detected even
after 11 years of
SARS-CoV-2
infection. More
studies are being
conducted to
understand the
protective role of T-
cells in controlling
SARS-Cov-2
infection (https://www.
nature.com/articles/s4 Fig. 4.2: Thymus.
1586-020-2550-z)
These two compartments of thymus are interconnected by a three-dimensional
network composed of epithelial cells, dendritic cells and macrophages. All
these three cells are responsible for the development of stromal cell network
that plays a significant role in the growth and maturation of thymocytes. Here it
is important to know about specific type of epithelial cells that are found in the
outer cortex that are known as nurse cells. These cells have long membrane
extensions and are surrounded by more than 50 thymocytes, altogether they
are responsible for formation of large multicellular complexes. Thymus also
exhibits a unique property of selecting the effective T cells that protect the
body from infection. You will know more about this process in Unit 9 where
you will be studying about major histocompatibility complexes (MHC) and their
78 importance in immune response.
It is important to remember that on the efficiency of thymus or thymic function
will be declining with growing age. This decline may be one of the reasons for
low immunity during old age in humans. It is interesting to note that the
average weight of thymus in infants is around 70 g whereas it is reduced to 3 g
in old people.
BONE MARROW
Bone marrow is the soft, spongy, highly vascular tissue found in the medullary
cavities of bones (Fig. 4.3 A). In humans it is primarily located in the regions
like ribs, vertebrae, sternum, and bones of the pelvis. In adults this site is
responsible for production of red blood cells, a process that is known as
haematopoiesis. Haemopoietic stem cell is the primary stem cell that are
responsible for production all other immune cells. It is interesting to know that
this Haemopoietic stem cells are found in foetal liver and bone.
Especially in mammals like humans and rats bone marrow acts as crucial site
for the origin and development (proliferate and differentiate) of B cells.
Whereas in case of bird’s bursa Fabricius, in case of cattle and sheep it is
the foetal spleen acts as primary lymphoid tissue for maturation proliferation
functions of B cells. Even in rabbit gut associated tissue like appendix acts as
primary lymphoid organ.
Structure of bone marrow
Bone marrow can be divided into two major components or parts the first one
is red marrow and the second one is yellow marrow. Red marrow is majorly
found in skeleton bone system and plays a significant role in the formation of
blood cells and also to remove the old cells from circulation. This part of the
bone consists of haemopoietic stem cells that in turn produce myeloid and
lymphoid stem cells. These cells in later stages divided into red blood cells
white blood cells and platelets. You will learn more about cells of immune
system in the next unit of this course.
Whereas the yellow marrow is predominantly found in soft bone region which
is also known as spongy bone. This part of bone marrow is known vascular
and consists primarily of fat cells. Though it possesses hemopoietic tissue but
it is physiologically inactive.
Microscopic observation of bone marrow depicts hemopoietic tissue islands

and adipose cells surrounded by vascular sinuses within a mesh work of
trabecular bone (Fig. 4.3 B). Structurally bone marrow can be divided into
vascular and non-vascular regions that are composed of both cellular and
non-cellular components. The non-vascular (peripheral) region is known for
haematopoiesis which is rich in cells of various lineages and stages of
maturity. The cells and tissues that are commonly found in this region include
fat cells, collagen fibres, fibroblasts, dendritic cells and bony tissues
(trabeculae). Whereas the vascular region (centre) is rich in blood vessels that
brings in nutrients and collects the mature blood cells into circulation.
Hence we can conclude that bone marrow is playing a significant role in

immune response by producing various lymphoid cells that migrate to
secondary lymphoid organs to divide further and also in maturation of B cells.
Platelets which play an important role in blood coagulation are also produced
in bone marrow. 79
Fig. 4.3: A. Bone marrow B. Microscopic view of Bone Marrow.
SAQ 1
Match the following:
Column A Column B
i) Thymus a) Haematopoietic stem cell
ii) Bone marrow b) protection from infection
iii) Nurse cells c) T cell maturation
iv) Selection effective of T cells d) Densely packed with immature
T cells
v) Cortex e) B cell maturation
vi) Primary stem cell f) formation of multicellular
complexes
vii) Non-Vascular tissue g) haematopoiesis
viii) Red bone marrow h) Collection of mature red blood
cells
4.4 SECONDARY LYMPHOID ORGANS

This group includes lymph nodes, spleen, mucosa associated lymphoid
tissues (MALT) and gut associated lymphoid tissue (GALT). Due to their
location in the body, they are known as the peripheral lymphoid organs they
mainly involved in trapping the antigen and act as sites for the interaction of
mature lymphocytes with antigen. Both lymph nodes and the spleen are
organised secondary lymphoid organs, as they have specific regions for T cell
and B cell activity and also surrounded by fibrous capsule, whereas MALT is
an unorganised or less organised. However, MALT is widely distributed in the
human body. Let us discuss these secondary lymphoid organs one by one.
i) Lymph nodes
These organs are bean shaped structures composed of reticular network that
80 is filled with lymphocytes, macrophages and dendritic cells (Fig. 4.4). Lymph
nodes are found at the junctions of lymphatic vessels (refer unit 3 of BZYCT-
135). Due to their widespread availability, they are the first organs to combat
antigens that enter into tissue spaces. The lymphatic fluid that is passing
through these nodes brings the antigens and these antigens will be exposed to
the phagocytic and dendritic cell network present inside these nodes.
Fig. 4.4: Lymphatic systemand Lymph node.
Lymph node consists of three regions the cortex, the paracortex and the
medulla. Where cortex contains B cells (Lymphocytes), macrophages and
follicular dendritic cells in their primary follicles (Fig 4.4). Once after interacting
with antigens the primary follicles convert into secondary follicle which is
comparatively large in structure and contains a germinal centre.
The para cortex rich in T lymphocytes also contains dendritic cells that have
migrated from surrounding tissues into the nodes. The last compartment that
is medulla that has a smaller number of lymphoid lineage cells and plasma
cells that are actively secreting antibodies.
If we put the entire mechanism that is taking place inside a lymph node it is
like, "the antigen is trapped, processed and presented to dendritic cells in the
paracortex which inturn activates T helper cells. Also, activation of B cells
takes place in the presence of T cell rich paracortex". These plasma B cells
are responsible for secreting Ig M and IgG antibodies. Phagocytic cells and
dendritic cells are responsible to trap bacteria or any foreign particle that is
coming into lymph node. It is interesting to note that this entire process
completes in a span of 4 to 7 days. It is also important to know that fluid
leaving lymph node through efferent lymphatic vessels is rich in antibodies and
concentration of lymphocytes.
ii) Spleen
Spleen located in the left abdominal cavity it is a large ovoid secondary

lymphoid organ (Fig. 4.5). Spleen please an important role in immune
response through producing antibodies. We have discussed in the previous 81
section that lymph nodes filter the antigens present in lymphatic circulation,
however, spleen is responsible to filter the antigens that are present in blood
circulation or blood borne antigens. Here it is important to know that spleen
plays a key role in systemic infections. Splenic artery brings in the blood along
with antigens, whereas splenic vein takes away the blood that is rich in
antibodies. There are two important compartments inside spleen like red pulp
and white pulp. The red pulp consists of sinusoid network, surrounded by
numerous macrophages, red blood cells and few lymphocytes. This site is
physiologically responsible for the breakdown of defective and dead RBCs,
whereas white pulp is rich in T lymphocytes forming a periarteriolar lymphoid
sheath (PALS).
The effects of splenectomy (a surgical procedure to remove spleen) on the

immune response depends on the age at which the spleen is removed. In
children, splenectomy often leads to an increased incidence of bacterial
sepsis caused primarily by Streptococcus pneumoniae, Neisseria
meningitidis, and Haemophilus influenzae. Splenectomy in adults has less
adverse effects, although it leads to some increase in blood-borne bacterial
infections (bacteraemia). Ref: Text book of Immunology by Janis Kuby.
Fig. 4.5: Spleen.
MUCOSAL-ASSOCIATED LYMPHOID TISSUE (MALT)
MALT is a diffuse system of small concentrations of lymphoid tissue found in

various submucosal membrane sites of the body. These sites include
the gastrointestinal tract, nasopharynx, thyroid, breast, lung, salivary
glands, eye, and skin. You would be surprised to know the size of MALT is
approximately 400 m2 (nearly the size of a basketball court). MALT lining
82 covers digestive system, respiratory system and urogenital system, that are
major sites of entry for the pathogens. These tissues include loosely arranged
lymphocyte clusters around villi and well organised tonsils (Fig. 4.6). MALT
can also be classified based on the tissues they are associated with: BALT
(Bronchus Associated Lymphoid Tissue), GALT (Gut Associated Lymphoid
Tissue), LALT (Larynx Associated Lymphoid Tissue), CALT (Conjunctiva
Associated Lymphoid Tissue), NALT (Nasal Associated Lymphoid Tissue),
SALT (Skin Associated Lymphoid Tissue), DALT (Duct Associated Lymphoid
Tissue) and LDALT (Lacrimal Duct Associated Lymphoid Tissues). Appendix,
and Peyer’s Patches found in the submucosal layers of the intestinal lining
(Fig. 4.7). MALT has the capacity to invade (endocytose) the antigens from the
lumen of the respiratory and urogenital tracts. Due to these immune abilities or
activities, antibodies are released immediately to fight against the antigens
that are entering into our body. It is important to know that, secretions of MALT
majorly consist of IgA antibody, hence it is known as secretory antibody.
Fig. 4.6: Types of Tonsil.
Fig. 4.7: Micro villi of gastrointestinal tract. 83

SAQ 2
Match the following
Column A Column B
i) Organised lymphoid organ a) Plasma B Cells
ii) Lymphoid cortex b) rich in T cells
iii) Lymphoid paracortex c) rich in B cells
iv) Secretory antibody d) Primary lymphoid organs
v) Dendritic cells e) Trapping bacteria
vi) Red pulp f) MALT secretions
vii) Spleen g) Break down of defective RBCs
viii) Ig A h) Filtering blood borne antigen
Some interesting Facts about our immune system:
Whenever you receive any vaccination or antibiotic through intramuscular

injection you might have noticed the development of small swelling/lesions at
the site of injection. Have you ever thought what would be the reason for this
swelling? This swelling is a by-product of interaction that is taking place
between antigen and antibody. In our daily life we came across so many such
incidents where our immune response combats with the antigens that are
entering into our body. Some of the examples include sneezing when smell
something strange and tears against the entry dust mites. These are a kind of
defence mechanisms that our body possess as a natural ability.
(Source: pinterest.com)
Have noticed the consequences that took place after meeting any minor
injury while playing football or any sport? If not, you will start observing after
going through this unit. Let us discuss one small such example, whenever we
suffer with small scratches on our elbows and toes (while playing in ground),
the next day morning we will notice swelling at the junction of thighs or under
arm pits. This swelling is due to the presence of lymph nodes at these
regions and their involvement in the battle against the antigens that might
have entered through the scratch.
You might have also heard about kids suffering from tonsils whenever they
84 consume something cold or exposed to allergens. Such people with
aggressive immune system are known as hypersensitive. Similar to this
adenoid is also one such response developed by our lymphoid organs.
(source:
https://www.aboutkidshealth.ca/Article?contentid=1220&language=English#a
rticle-intro)
You might be surprised to know that the rise in body temperature during any
infectious disease or condition is could be due to the immune reactions
(production of antibodies) that are taking place in your immune system and
the fight exhibited by antibodies against the antigens that entered into your
body. Hence, the rise in body temperature indicates that your immune system
is responding to the infection that has entered your body. Last but not the
least the lesions developed against mosquito bite or bee sting are also part of
our immune response.
(source: https://health.clevelandclinic.org/)
4.5 SUMMARY
In this Unit you have studied:
• Primary lymphoid organs namely thymus and bone marrow are

responsible for the development of immune cells.
• Primary lymphoid organs can be assumed as the centres or points

where the production of immune cells occurs.
• Thymus being a small organ in the body is responsible for the

maturation of T lymphocytes.
• Bone marrow plays a vital role in the process of haematopoiesis where it

produces various lymphoid cells.
• Bone marrow is the site from where B cells are produced. The
secondary lymphoid organs like lymph nodes, spleen and mucosa
associated lymphoid organs ate the sites of immune response.
• The secondary lymphoid organs can be considered as battle grounds

where the actual antigen antibody interaction takes place. 85
1. Write a detailed note on the lymphoid organs that are involved in the
maturation of lymphocytes.
2. Describe the structure of bone marrow with a neat diagram.
3. Write a comparative note on the role of Thymus and Bone marrow with
respect to immune response.
4. Draw a neat labelled diagram of spleen.
5. Compare and contrast primary and secondary lymphoid organs.
4.7 ANSWERS
1. i) c, ii) e, iii) f, iv) b, v) d, vi) a, vii) g, viii) h.
2. i) d, ii) c, iii) d, iv) a, v) e, vi) g, vii) h, viii) f.
Terminal Questions
1. Refer to Section 4.3.
2. Refer to Fig. 4.3.
3. Refer to Section 4.3.
4. Refer to Fig. 4.5.
5. Refer to Sections 4.3 and 4.4.
86
Unit 5 Cells of the Immune System
UNIT 5
CELLS OF THE
IMMUNE SYSTEM
Structure
5.1 Introduction 5.6 Cells of lymphoid lineage
Objectives Lymphocytes (T and B cells)
5.2 Hematopoietic Stem Cells Natural killer cells
5.3 Hematopoiesis 5.7 Epitope- Antigen
Genetic Regulation of Determinants
Haematopoiesis 5.8 Summary
Growth Factors in 5.9 Terminal Questions
Haematopoiesis 5.10 Answers
Nexus between Hematopoiesis
and Apoptosis
5.4 Cells of the immune system
5.5 Cells of Myeloid Lineage
Granulocytes
Phagocytic cells
5.1 INTRODUCTION
Immune system is a congregation of cells and organs that functions to provide
immunity against microbial infection. Primary and secondary lymphoid organs
in human or vertebreate body constitute the immune system. Primary organs
provide the conditions neccessary for the production and maturation of cells
involved in immune response. The secondary organ provides the platform for
interaction of antigens and mature lymphocytes. The two organs of immune
system are interconnected through network of blood vessels and lymphatic
ducts through which cells of immune system circulates to all the tissues and
organs of the body. Therefore the cells of immune system are in constant
patrol and looking for pathogens. On locating a pathogen/ antigen, they
multiply and release alert signals to other cells of immune system. The vital
role of recognition of self/ non-self, diversity of forms, specificity for antigens is
possessed by lymphocytes. The other leucocytes play the ancillary functions, 87
such as activating lymphocytes, efficient antigen clearance through
phagocytosis, or secreting different immune-effector molecules. The present
chapter would concentrate on the development of blood cells, properties of the
various cells of immune system, and their interaction with antigens.
Objectives
 discuss the process of generation of immune cells,
 explain regulation of production of immune cells,
 describe characteristics and functions of various immune cells,
 explain mechanism of immune responses and
 discuss the properties of Antigen Recognized by the B and T cells.
5.2 HEMATOPOEITIC STEM CELLS

Blood cells of our immune system that are formed from stem cells are known
as hematopoietic stem cells (HSCs). The term hematopoiesis refers to the
process of formation of blood cells, their development and differentiation.
Hematopoietic stem cells (HSC) are pluripotent cells which have the ability to
Pluripotent cell has differentiate in various different blood cells types like granulocytes,
two properties: Self
erythrocytes, mast cells, monocytes, megakaryocytes and lymphocytes (Fig.
renewal and
5.1). However, the hematopoietic stem cells have very low population in the
potency. They are
capable of giving bone marrow (less than 1 HSC per 5x104 cells). The study of HSC is still a
rise to several challenge due to its difficulty to growing them in vitro conditions.
different cell types.
The HSC remains at a stable level even during adult life due to its ability of
self-renewal; however, hematopoietic stem cells exhibit tremendous
proliferative potential when there is an increased demand by the body. HSCs
develop and mature in the stromal cells meshwork of bone marrow. These
stromal cells includes lipocytes, endothelial cells, fibroblasts and
macrophages. Stromal cells are non-hematopoietic but nurtures the growth
and differentiation of HSCs. They influence stem cell differentiation by
providing a cellular matrix and factors that promote growth and differentiation -
hematopoietic-inducing microenvironment (HIM).
Hematopoietic stem cells are pluripotent cells which are able to differentiate in
various different blood cells types.
Most of these hematopoietic growth factors are soluble agents that enter their
target cells through diffusion or through receptors on the surface of stromal
cells that are involved in cell-to-cell communication between the reacting cells
and the stromal cells. During infection, activated T cells and macrophages
induce hematopoiesis by producing hematopoietic growth factors. An average
human being is estimated to produce 3.7X1011 blood cells every day to
maintain steady state levels in the peripheral circulation. During hematopoiesis
cell division and differentiation are regulated by apoptosis, the programmed
88 death of cells. Failure in apoptosis may result in leukemia.
Fig. 5.1: Haematopoiesis. 89

5.3 HEMATOPOIESIS
In humans, during fetal stage hematopoiesis begins in the first weeks of
embryonic development during the yolk sac stage. Then HSC migrates to liver
from the yolk sac and subsequently to the spleen. Therefore, during the third
to seventh months of gestation this two organs play vital roles in
hematopoiesis (Table 5.1).
Thereafter, bone marrow becomes the primary hematopoietic organ, and

hematopoiesis in the liver and spleen ceases. The multipotent hematopoietic
stem cells differentiate to give rise to either a common myeloid or lymphoid
progenitor cell. The differentiation of stem cell is determined by its
microenvironment in terms of the nature and amount of growth factors. The
ability for self-renewal in HSC is lost once they differentiate into progenitor
cells and the fate of their cell lineage gets fixed. A common lymphoid
progenitor cells give rise to Lymphoidal cells like B-cells, T-cells, NK (Natural
Killer) cells and some dendritic cells arise from common lymphoid progenitor.
Red blood cells (erythrocytes) and other white blood cells are generated from
myeloid stem cells.
5.3.1 Genetic Regulation of Hematopoiesis

The differentiation of pluripotent HSC into different types of cells involves the
expression of lineage-specific genes in specific order at specific time period.
The product of these genes control stem cell differentiation and act as critical
components of regulatory networks. Studies using “knockout” mice
(replacement or disruption of an existing gene using an artificial piece of DNA)
has helped in understanding the genetic regulation of hematopoiesis. When
specific gene is knocked out, it failed to generate RBC or specific WBC in the
mice. Therefore, it can be inferred that this gene is essential for the
development of those cells. Although much remains to be done, number of
transcription factors playing important role in hematopoiesis has been
identified using this technology. Some of these transcription factors control
and regulate several or only single hematopoietic lineages of lymphocyte
90 development. GATA-2, a family member of transcriptional factor which
recognizes a nucleotide motif in target gene that has GATA sequence is one
such transcription factor that influences several lineages. A functional GATA-2
gene encoding factor is vital for the development of lymphoid, myeloid and
erythroid lineage. Hence, in animals with GATA impaired gene, the progeny
gets determinate during the embryonic development period. While
transcription factor Ikaros, unlike GATA-2 is crucial for the development of
lymphoid lineage cells only. In Ikaros knockout mice, the production of myeloid
lineage erythrocytes, granulocytes, and other cells are unaffected and
therefore, they survive embryonic development. Nevertheless, they display
severely compromised immunity . Usually they die at an early age from
infection as they are not able to produce substantial amount of B, T, and NK
cells (Table 5.2).
5.3.2 Growth Factors in Haematopoiesis

The hematopoietic cells in culture require a variety of growth factors for their
survival, proliferation, differentiation and maturation. They are also known as
hematopoietic cytokines. These factors are recognized from their ability in
promoting formation of colonies in a bone-marrow culture. Colony Stimulating
Factor (CSF), a family of acidic glycoprotein is one of the first cytokines to be
identified. Another significant hematopoietic cytokine produced in the kidney is
erythropoietin (EPO). Erythropoietin is a glycoprotein that plays significant role
in inducing production and regulating terminal development of RBCs. Studies
have revealed that the capacity of cytokine in promoting growth and
differentiation depends on the presence of cytokine receptors in the target cell.
Therefore, the fate of progenitor cell is directly related to the type of receptors
on the cells surface that are unique to that cytokine. Many different cytokines
and their receptors play important roles in inducing cell proliferation, promoting
differentiation, maturation, preventing apoptosis and functioning of mature cell.
Several other growth factors also function at different stages of
haematopoiesis. Some important growth factors are mentioned in the table
below (Table 5.3). 91
Hematopoiesis naturally maintains a steady-state between the development of

mature blood cells and loss mainly due to aging. It is estimated than an
average human being must produce 3.7 x 1011 WBCs per day to maintain
steady-state levels. White blood cells have differential life spans; for instance
certain T lymphocytes live from a few days to 20-30 years for neutrophils.
However, erythrocyte life span is about 120 days before being phagocytised
and digested in the spleen. To maintain the steady state level of different
blood cells, hematopoiesis is regulated by complex mechanism. In emergency
condition, during haemorrhages or infection, there is an inbuilt adaptability of
rapid cell production by ten to twentyfold. Management of steady-state
hematopoiesis is carried out in various ways, including: precise quantity and
class of cytokines that is released by stromal cells of bone marrow, cytokines
produced by activated T cells and macrophages having hematopoietic activity,
controlled expression of receptor in stem cells and progenitor cells for
hematopoietically active cytokines.
A failure in either of these regulatory frameworks or a combination of them can

have significant consequences. Anomalies in the production of hematopoietic
cytokines or expression of their receptors may lead to unchecked cell
proliferation contributing to the development of leukemia Finally, in every
hematopoietic family the number of cells recruited through cell division and
cells destroyed by cell death maintains the cells population. The rate of cell
proliferation and differentiation can be affected by one or a combination of
regulatory factors. Therefore, the fate of a hematopoietic cell to die is also
decided by these factors.
5.3.3 Nexus between Hematopoiesis and Apoptosis

Cells actively bring about their own demise by an induced and ordered
process called programmed cell death (PCD) or apoptosis. Programmed cell
death is a very crucial for steady-state maintenance of different types of cell
populations.
A number of molecular steps are involved during apoptosis, such as

intracellular protein activation, cell shrinkage, chromatin content condensation,
nuclear fragmentation, cleavage in a cell of intra-nucleosomal genetic material,
lead to its death. Each white blood cells has a distinct life span after which
they die by programmed cell death. For instance, blood circulating in an adult
92 human contains around 5x1010 neutrophils which have a life span of just a few
days until the onset of programmed cell death. Therefore, death of the cells
along with the continuous production of neutrophils, maintains a steady state
of cells number. Leukemia would develop if programmed cell death does not
occur. Hence, PCD plays a vital role in keeping a check on proper numbers of
hematopoietic progenitor cells. Death of cells can be PCD or from natural
process of aging and damage which is termed as necrosis. The former, i.e,
Apoptosis is distinctly different from necrosis (Fig. 5.2). In necrosis, the
damaged cell swells and burst losing its contents which then initiates a harmful
inflammatory reaction.
Fig. 5.2: Schematic diagram depicting internal cellular changes occurring

during. apoptosis (Fig a) and necrosis (Fig. b).
SAQ 1
State whether the following statements are ‘True’ or ‘False’:
i) Hematopoietic stem cells are pluripotent cells.
ii) Stromal cells affect hematopoietic stem cell differentiation by providing a

hematopoietic- inducing microenvironment.
iii) Necrosis, the cell death-related changes that arise from damage.
iv) Myeloid stem cells generate progenitor cells of lymphocytes and NK

cells.
v) In humans, during fetal stage hematopoiesis begins in the yolk sac for
first weeks of embryonic development.
93
5.4 CELLS OF IMMUNE SYSTEM
You have already studied in this courses that our immune system can be
divided into two types of responses; innate immunity and adaptive
immunity/acquired immunity. The innate immune response is a nonspecific
first line of defence. It is a highly complex integration of various components.
Cells that are involved in innate immune response comprises of neutrophils,
basophils, eosinophils, dentritic cells, mast cells and macrophages. Adaptive
immune response is a very specific response as it tailors its attack to a specific
antigen previously encountered. Adaptive immune response is mediated by B
lymphocytes, T lymphocytes and Natural killer cells. In general, the immune
response requires three types of cells, namely lymphocytes, leukocytes (white
blood cells) and monocytes (Table 5.4). The diverse collection of immune cells
arise from multipotent HSC which differentiates to either a myeloid lineage
cells or lymphoid lineage cells.
5.5 CELLS OF MYELOID LINEAGE

Cells from the myeloid lineage are derived from a common myeloid progenitor
in the bone marrow during haematopoiesis. Myeloid lineage is a primary
component of the innate immune system – the non-specific, first line of
defense. Four types of cells arise from common myeloid progenitor cells:
megakaryocytes, erythroblast, myeloblast and monoblast. The large
multinucleated megakaryocytes cells produce platelets, which are necessary
for normal blood clotting. Erythroblast give rise to Red blood cells (RBC).
Myeloblast differentiates to form the effectors of the granulocytes including
neutrophils, eosinophils and basophils. Monoblast cells mature into monocytes
which, in turn, develop into macrophages. White blood cells have primary
function of protecting the body from infection. Bone marrow produces white
blood cells, and organs including spleen, liver, and kidneys regulate their
growth levels. These cells types are broadly characterized into granulocytes
and agranulocytes based on the presence or absence of cytoplasmic
94 granules or sacs.
5.5.1 Granulocytes
Granulocytes are large spherical shaped cells with characteristic lobed nuclei.
Their membrane-bound cytoplasmic granules get stained very precisely with
Wright's stain. Granulocytes are to a greater or lesser degree, phagocytic cells
with much shorter-life span as compared to erythrocytes.
There are three types of granulocytes (Fig. 5.3):
• Neutrophils: They are the most abundant white blood cell constituting
about 50 – 70% of circulating WBC. They arise from myeloid progenitor
cell. The nuclei of neutrophils consist of three to six lobes and due to this
nuclear heterogeneity are often referred to as polymorphonuclear
leukocytes (PMNs). Since the granules of neutrophils take up both
acidic and basic dyes they are termed as neutrophils. Neutrophils are
the first cells to arrive at infection site. Neutrophils are drawn to
inflammation sites and phagocytic cells that engulf and destroy target
cells under the influence of chemotactic factors stimulated by tissue
damage (complement protein, clotting proteins and T cell derived
cytokines). They release their granules which acts as lysosomes
digesting cellular macromolecules and also cause self-destruction.
• Eosinophils: Eosinophils constitute 2-4 % of the circulating white blood

cells and are around the size of neutrophils. The nucleus of eosinophils
is bi-lobbed having a U-shaped appearance under microscope in blood
smears. The cytoplasm is granular which stains from brick red to
crimson with acidic dyes. Typically, eosinophils are located in the
stomach and intestinal connective tissues. They are phagocytic in nature
targeting the antigens bound with antibody. This antigen-antibody
complex signal the destruction of antigen by eosinophils. Eosinophils are
active particularly during parasitic infection like helminths and release a
toxin called Major basic protein, which help in removal of the parasite
from the body.
Fig. 5.3: Morphology of granulocytes. a) Neutrophil b) Eosinophil c) Basophil.
• Basophils: Basophils are found in the blood in low numbers with an

average of just 0.5–1 %. The nucleus is mutli-lobed and the cytoplasm
contains large, coarse granules containing histamine which have an
affinity towards basic dyes. Cross-linking of the IgE causes the basophils 95
to release histamine. Histamine, an active mediator of blood vessel
dilation, causes increased blood flow and capillary permeability to
facilitate rapid transfer of white blood cells to infected areas.
• Mast Cells: Mast cells are released as undifferentiated cells into the
blood during hematopoiesis. They only undergo differentiation after
leaving the blood stream and enter into tissues. Mast cells are
abundantly found in the connective tissues of different organs,
respiratory, genito-urinary, digestive mucosal epithelial tissues and skin.
Like basophils, they possess histamine containing cytoplasmic granules
in large numbers. These granules also contain important
pharmacologically active mediators. Mast cells, along with basophils
from the blood play an important role in allergy development.
5.5.2 Agranulocytes
Agranulocytes are the white blood cells that lack visible granules in their
cytoplasm and have characteristically larger nucleus. There are two types of
agranulocytes: Lymphocytes arsing from common lymphoid progenitor cells
and monocytes from common myeloid progenitor cells. Monoblast cells of
myeloid lineage mature into monocytes which, in turn, develop into
macrophages (Fig. 5.4).
Monocytes: Monocytes constitute 3-8 % of white blood cells. They are the
greatest in size amongst the white blood cells and have an average diameter
of 18 μm. They have pale-blue cytoplasm and a darkly stained purple nucleus
that is distinctly U-shaped or kidney-shaped. They differentiate into extremely
mobile macrophages or dendritic cells with remarkable appetites as circulating
monocytes migrate from blood to tissue.
Macrophages: Macrophages are found scattered in the body, some

macrophages take up residence in specific tissues and become fixed
macrophages and others remain motile as free/ wandering, macrophages.
Free macrophages migrate across the tissues by amoeboid movement.
Differentiation of a monocyte into a tissue macrophage involves a number of
changes like five to tenfold enlarged cell size; increase in both number and
complexity of the intracellular organelles; and attaining increased phagocytic
capacity, higher levels of hydrolytic enzymes production, and secretion of a
number of soluble factors.
96 Fig. 5.4: Typical Morphology of a) Monocyte b) Macrophage.

In several tissues, macrophage-like cells perform various roles and are termed
accordingly. Macrophages found in the lungs are termed as alveolar
macrophages, those found in the connective tissues are termed as
histiocytes, Kupffer cells in liver, mesangial cells, osteoclast, and
microglial cells in kidney, bones, and brain respectively. During resting
state, a number of stimuli activate macrophages. The initial activating stimulus
is the phagocytosis of a particulate antigen. The function of macrophage may
be further enhanced by cytokines and activators like IFN-γ secreted by
activated helper T cells. In contrast to resting macrophages, activated
macrophages show greater efficiency in tackling the impending pathogens.
These activities include; improved capability in killing phagocytosed microbes,
enhanced inflammatory mediators production, and improved capacity for T
cell activation. Furthermore, they secrete different cytotoxic proteins that aid
killing of a wide variety of pathogens, including intracellular bacteria, virus-
infected cells and tumour cells. These activated macrophages also show
higher expression of MHC class-II molecules allowing them to behave as
antigen-presenting cells more effectively.
Fig. 5.5: Phagocytosis and exogenous antigen processing by macrophage.
Antigens that are not of intracellular origin – exogenous antigen and antigens
whose source of origin is intracellular – endogenous antigen may be ingested
and digested by macrophages. During phagocytosis, initially macrophages get
attracted and migrate towards various chemical substances produced in an
immune response by chemotaxis. In the next step of phagocytosis, the antigen
gets adhered to the macrophage cell membrane after which membrane
protrusions stretch around the attached material, called pseudopodia.
Pseudopodia encircle the attached antigen and fuse with the membrane
forming a structure called phagosome. A phagosome moves towards the
interior region of the cell and fuses with lysosome. The structure thus formed
is called phagolysosome. Lysosome releases hydrolytic enzymes and
lysozyme that digest the ingested material which is then eliminated by process 97
of exocytosis. Macrophages can also deploy alternate mechanism through
which antigens could be made more susceptible to phagocytosis. This
mechanism is known as Opsonization. In opsonization, an antigen say a
bacteria is coated with a appropriate antibody forming an antigen-antibody
complex. A second antibody forms a link between the antigen-antibody
complex and receptor present on the macrophage membrane. The antigen-
antibody complex readily binds to macrophage receptor due to high affinity of
the second antibody with the receptor than the complex alone. Hence, this
results in enhanced phagocytosis (Fig. 5.6). Therefore such molecules that
bind to both the antigen-antibody complex with the macrophage to improves
phagocytosis are known as opsonin.
Fig. 5.6: A phagocytic cell recognizes the antibody (opsonin) on the surface of
an antigen.
Dendritic cells: Dentritic cells (DC) are located in skin, inner layers of the
nose, lungs and gastrointestinal tract. Dentritic cells are identified easily
from their characteristic projection of membrane that give the appearance
similar to the dendrites of nerve cells. There are four types of dendritic cell
(Fig. 5.7). They are: Langerhans cells, intestinal and myeloid dentritic cells
arising from myeloid lineage and lymphoid dentritic cells from lymphoid lineage
of HSCs at different location. All the four types of dentritic cells constitutively
expresses class II MHC molecules and B7 (co-stimulatory molecules) in high
levels. Hence, the DCs are much efficient than other APCs which require
trigger to function as an antigen presenting cells. The immature DC acquires
and processes the antigen through phagocytosis or endocytosis and mature
98 dendritic cells present it to T helper cells.
Fig. 5.7: Dentritic cell lineage from HSC.
Following microbial invasion or during inflammation, DCs of common myeloid

progenitor (Langerhans and interstitial) migrate and drain into lymph nodes for
presenting antigens to Helper T Cells. Some dentritic cells found in the lymph
follicle of lymph nodes which are rich in B cells. They are called Follicular
dendritic cells due to their exclusive location in the lymph follicles of lymph
nodes region. Unlike other dendritic cells, these cells do not participate in
antigen presentation since they lack MHC class II molecules on their
membrane. On the contrary, they show high level of antibody receptors on
their membrane for the binding of antigen-antibody complexes. These immune
complexes present in the blood stay in the blood for longer duration and hence
leads to an effective immune response.
SAQ 2
Fill in the blanks:
(i) ……………… cell has bi-lobed nucleus that appears U shape in blood
smear.
(ii) Macrophage in the liver is called ………………… cell.
(iii) ……………… dendritic cells lack MHC class II in its membrane, hence
do not participate in antigen presentation.
(iv) …………… act as opsonin which improves the process of phagocytosis

by macrophages.
(v) ………………. are the first cells to arrive at infection site.

99
5.6 CELLS OF LYMPHOID LINEAGE
The elemental cells of the immune system responsible for adaptive immunity
are the Lymphocytes. They are derived from a common lymphoid progenitor
cells. Lymphocyte possesses fundamental immunological trait of specificity,
memory, diversity and recognition of self/nonself. Lymphocytes constitute the
second most numerous white blood cells which is about 20-40% of the white
blood cell population. Morphologically, lymphocyte is characterized by dark
purple stained, spherical shaped, large nucleus slightly depressed that
occupies most of the cell volume with a pale blue cytoplasm. Lymphocytes are
in constant circulation (blood and lymph) through the tissues spaces and
lymphoid organs thereby integrating the immune system to a high level.
Lymphocytes can be divided into B cells, T cells and natural killer (NK) cells
based on their function and cell-membrane components. Unlike B and T cells
which possess surface marker, NK cells are large granular lymphocytes
without surface markers. Resting lymphocytes are usually small-sized naive
lymphocytes with densely packed chromatin, poorly developed endoplasmic
reticulum and Golgi apparatus and a few mitochondria. Once, the antigen is
encountered by naïve lymphocytes, these resting lymphocytes are triggered to
proliferate. Hence, the cell cycle arrest is withdrawn and these cells enter the
cell cycle. During this process, lymphocytes enlarge thrice its size and also
organellar complexity is enhanced and these are named as lymphoblasts
(Fig. 5.8).
Fig. 5.8: Fate of antigen-activated small lymphocytes.
5.6.1 B lymphocytes
B cells were first discovered in the lymphoid tissue called ‘Bursa of Fabricius’
which is a tissue associated with gut in birds. In humans and mice B cell
maturation takes place in bone marrow. After maturation, B cells migrate to
secondary immune organs. B cells constitutes about 10-15% of circulating
lymphocytes. B cells on encountering with an antigen, bind with the antigen
through their membrane receptors called B cell receptors (BCR). This
interaction stimulates rapid division of B cells and differentiation into Plasma
and memory cells (Fig. 5.9). Numerous identical copies of antibodies specific
to the antigen are produced and released into the bloodstream by these
plasma cells to target the circulating antigens. For the same antigen, memory
100 B cells develop immunological memory to impart enhanced reactivity to the
same antigen on the second encounter. In order to kill the antigen, the B cell
immune reaction requires the synthesis of antibodies in the blood and lymph,
hence, it is also often referred to as humoral immune response (humor, or
body fluid). Memory B cells have a long life span, therefore, provide life-long
immunity against many pathogens. Production of antigen specific antibodies
and antigen presentation to T helper cells for their activation are the two most
significant functions played by B cells in providing the protection to the body.
Fig. 5.9: Development of memory B cells and plasma cells.
Mature B cells display different molecules on their membrane. They are;
i) CD45 is form B220: Marker protein present in mature and immature of B

cells. It is, however, not expressed specifically by B-lineage cells, unlike
antibodies.
ii) Class II MHC: Facilitate the B cell to serve in presenting antigens.
iii) CR1 and CR2: Complement receptors for binding of complements and
its products.
iv) CD32: Receptors for antibody class G (IgG) also designated as FcγRII.
v) B7-1 and B7-2: Membrane proteins that interact with TH cell membrane
receptors (CD28, CTLA-A).
CD40: Costimulatory protein required for the activation of antigen presentation

and crucial role in the survival and production of plasma cells or memory cells.
5.6.2 T Lymphocytes
T lymphocytes or T cells like B cells originate from the bone marrow. They
migrate to thymus gland, where they undergo maturation. T lymphocytes
response to antigens is responsible for the adaptive immunity or cell-mediated
immunity. Unlike humoral immunity, where B cells possess the capability to
bind with soluble antigens, T cells cannot bind on its own in cell-mediated 101
immunity. They require major histocompatibility complex (MHC) molecules
to present the antigens. MHC molecules are expressed on the cell surface of
APCs or cancerous cells or virus infected cells.
T cells can be identified by the presence of two membrane molecules, namely

CD4 and CD8 (Fig. 5.10). The CD4 are limited to recognising antigens that are
bounded to class II MHC, CD8 is limited to recognising antigen with MHC
class I molecules. Additionally, the following membrane molecules are
expressed by most mature T cells:
 CD28: a receptor responsible for co-stimulatory function with molecules

of B7 family that are present in antigen presenting cells.
 CD45: Tyrosine phosphatase type receptor, present abundantly in T

cells as intergral membrane protein.
Fig. 5.10: Characteristic membrane molecules on lymphocytes. (a) B cells

possess membrane-bound antibody (b) T helper cells (TH) bear CD4
membrane receptors (c) T Cytotoxic cells (TC) bear CD8 membrane
receptors.
There are mainly three sub-populations (Fig. 5.11):
1. Helper T cells (TH): T cells expressing CD4 molecules are called TH

cells. They are restricted to recognising only those antigens bound to
MHC class II molecules.
2. Cytotoxic T cells (TC): T cells expressing CD8 molecules are called TC

cells.
3. Suppressor T cells (TS): TS are specific T cells involved in suppressing

humoral and cell-mediated immune responses.
The activation of T cells therefore, requires specific conditions since TC and TH

cells are restricted to antigens presented through Class I and II MHC
molecules respectively. When TC cells get activated they result in proliferation
and differentiation into effector and memory T cells. Activation of TH cells
produces cytokines (growth factors) that stimulate B cells to proliferate and
generate antibodies, trigger macrophages, and T cytotoxic cells to destroy
antigen/cells. TC cells on activation proliferate and differentiate into cytotoxic
102 T lymphocyte (CTL), under the influence of TH-derived cytokines. The CTL
does not typically secrete many cytokines unlike like the TC cell, instead they
display cytotoxic or cell killing activities. The CTL plays a crucial role in
tracking the body's cells and removing any antigen-showing cells, such as
virus-infected cells, tumour cells, and tissue graft cells. Those cells that display
antigens-MHC class I complex are referred to as altered self-cells; these are
CTL targets.
Fig. 5.11: Antigen presentation by MHC molecules TC cells and TH cells.
5.6.3 Natural Killer Cells (NK cells)

Natural Killer cells constitute about 5 to 10% of the total lymphocyte
population. NK cells do not exhibit specific membrane receptors or molecules
like the T and B cells lines. They use different strategies to identify potential
target cells. Anomalies like a reduced Class I MHC molecules display,
irregular profile of surface antigens that some tumour cells and some virus
infected cells exhibit are determined by the receptors of the NK cells. An
alternative approach through which NK cells identify and destroy possible
target cells is antibody-dependent cell mediated cytotoxicity. In certain tumor
cells and virus infected cells, antibodies binds with the antigens that are
displayed on the cell surfaces against which antibody mediated immune
response can be produced. NK cells express CD16 membrane receptor for
antibody (IgG) Fc region and hence, they are able to bind to these antigen
coated antibodies and eventually kill these targeted cells (Fig. 5.12). 103
Fig. 5.12: Schematic illustration of Antibody-dependent cell-mediated

cytotoxicity (ADCC) mediated by NK cells.
5.7 EPITOPES-ANTIGENIC DETERMINANTS

Immune cells do not interact with the entire antigen but interact with discrete
region of an antigen. These immunologically active regions of the antigen are
recognised primarily by B and T-lymphocytes, as well as free molecules of
antibodies which are known as epitope or antigenic determinant. Studies with
small antigens have shown that diverse epitopes present on the same
antigenic molecule can be recognised by B and T cells. However, the mode of
antigen recognition is distinctive, where a soluble antigen is recognised by
antibody in case of B cells. In case of T cells, recognition is made possible
through display of antigens peptides on MHC molecules of APCs and altered
self-cells. Therefore, the epitopes must be highly accessible and exposed to
the surface on the antigen.
5.7.1 Properties of B Cell Epitopes

The ability to function as a B cell epitope depends on the nature of antigen
binding site on antibody molecules of B cells. The interaction between B cells
and the antigens involves a binary complex comprising of antibody, the
membrane receptor and antigen by a weak non-covalent interaction (Fig.
5.13). Hence, having complementary shape is required for the formation of
binary complex between the binding site of the antibody and the epitope. This
104 criterion presents certain constraint on the epitope's properties.
The size of the epitope is always smaller than the antibody binding site and
the shape of the epitope recognizable by the antibody is determined by the
amino acid sequence of the binding site and the chemical environment they
generate for any given antigen-antibody reaction. For a proper binding of
antigen-antibody, the epitope of B cell should possess on its protein surface a
protruding region that is accessible. These regions are usually rich in
hydrophilic amino acids. The sizes of B cell epitopes are not constant. B cell
epitope proteins are generally large and often associated with the antibody
molecule with a larger, flatter, complementary surface. Also, complex proteins
comprise numerous overlapping epitopes of B cells, some of which are
immuno-dominant. Often, small ligand gets itself attached to antibody’s deep
pocket region. These ligands include, carbohydrates, haptens,
oligonucleotides and peptides.
Fig. 5.13: Interaction between B cells and the antigens involves a binary
complex.
5.7.2 Properties of T cell Epitopes

Soluble native antigens are not recognised by T cells directly. However, when
the antigens are processed into antigenic peptides and presented on MHC 105
molecules they can be recognized. The T cell recognized antigenic peptide
forms a tri-molecular complex of MHC molecule-antigenic peptide-T cell
Receptor (Fig. 5.14). T cell epitopes are mostly internal and are exposed as
antigenic peptides after undergoing processing inside APCs or altered self-
cells.
Fig. 5.14: Tri-molecular Complex of TCR-Antigenic peptide-MHC molecule.
5.8 SUMMARY
In this unit you have studied:
• Various types of white blood cells are present in our body and they play
an important role in immune response. Lymphocytes are the
fundamental immune cells that possess immunological features.
• Blood cells originate from hematopoietic stem cells. Progenitor stem

cells arise from the HSC which further differentiate into other specific
forms of cells.
• During hematopoiesis, the stem cell differentiation involves the

expression of various genes and transcription factors that establish the
lineage. Several hematopoietic growth factors (cytokines) cause various
blood cells to proliferate and differentiate.
• To maintain a steady-state of blood cells population, hematopoiesis is

closely regulated. The programmed cell death balances each of the
lineages' cell division and differentiation.
• Macrophages and neutrophils are specialised phagocytotic cells.

Opsonization promoted by antibodies coating antigen enhance the
phagocytosis.
• Activation of macrophages secrete factors that mediate adaptive

immune response. They also present antigens to TH cells through class
106 II MHC molecules.
• Dendritic cells play an important role in the activation of TH cells along
with macrophages and B cells by processing and presenting antigen
bound to class II MHC molecules and by supplying the required co-
stimulatory signal. Unlike the other dendritic cells, follicular dendritic cells
promote the activation of B cells but play no role in the activation of T
cells.
• Lymphocytes are differentiated into three forms namely, B cells, T cells

and natural killer (NK) cells based on the presence or absence of
specific membrane receptors.
• B and T lymphocytes form the central cells of adaptive immune

response. On encountering antigens they undergo proliferation and
differentiation into effector and memory cells.

1) What is hematopoiesis?
2) Differentiate between the B and T cells epitopes.
3) Expand the following:
(i) ADCC (ii) CTL (iii) MHC (iv) TCR (v) PMNs
5.10 ANWERS
1. True and False
(i) True, (ii) True, (iii) True, (iv) False.
(i) Eosinophils, (ii) Kuffer cells, (iii) Follicular, (iv) Antibodies
(v) Neutrophils.
Terminal questions
1) Hematopoiesis refers to the production of all types of blood cells
including formation, development, and differentiation of blood cells from
hematopoietic stem cells.
2) Refer to Table 5.5.
3) i) Antibody-dependent cellular cytotoxicity
ii) Cytotoxic T lymphocyte
iii) Major histocompatibility complex
iv) T-cell receptor
v) Polymorphonuclear leukocytes.
107
SUGGESTED READINGS
1. Judith A Owen; Jenni Punt; Sharon A Stranford; Patricia P Jones; Janis
Kuby. Text book of Immunology, New York: W.H. Freeman, ©2013. 7th
edition.
2. Online Education Resources.
3. Kuby Immunology. W. H. Freeman & Co. Fourth edition, 2000. 670

pages.
4. Immunology by Ivan Roitt, Jonathan Brostoff, and David Male. Mosby,

London. 6th edition, 2001. 480 pages.
5. Basic Immunology by Abul K. Abbas and Andrew H. Lichtman,

Saunders, 2001. 309 pages.
6. Kuby Immunology 8th edition by Punt, Stranford, Jones and owen. W,H,
Freeman McMillan learning., New York.
7. The Cell: A Molecular Approach by Geoffery M Cooper, 8th edition,

Oxford University Press.
8. Owen, J. A. Punt, J. Stranford, S. A. Jones, P. P and Kuby, J. (2013).

7thEdition Kuby Immunology. New York, USA: W.H. Freeman and
Company. ISBN-13: 97f8-1429219198.
9. Delves, P.J. Martin, S.J. Burton, D.R. and Roitt, I. M. (2017). 13thEdition.
Roitt’s Essential Immunology. New Jersey, USA: Wiley-Blackwell
Science. ISBN: 13: 978- 1118415771.
Acknowledgement of Figures
1. All figures of Units 1, 2 and 3 are drawn by Dr. Shivani G. Varmani,
Department of Biomedical Science, Bhaskaracharya College of Applied
Sciences University of Delhi, Delhi-110075.
2. All figures of Unit 5 are drawn by Dr. Indrakant K. Singh and Dr. Moses
Rinchui N., Department of Zoology, Deshbandhu College University of
Delhi, Delhi-110019.
108

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BZYET-141

Immunology deals with physical, chemical and physiological characteristics of the

Pathogens produce diseases in humans by the colonisation of host tissues or by liberating

• trace the course of development of the field of immunology,

4 • explain an overview of the immune system,

• list the various innate immunity barriers,

• discuss the functions of NK cells,

• define complement system and list its functions,

• explain various complement activation pathways,

• gain an insight about the adaptive immune system,

• differentiate between naturally and artificially acquired immunity,

• explain B and T lymphocytes,

• differentiate between humoral and cell-mediated immunity,

• compare and differentiate functions executed by primary and secondary lymphoid

• enlist the biological significance exhibited by lymphoid organs,

• discuss the properties of antigen recognized by the B and T cells,

• list the structure and properties of antigens,

• differentiate between T and B epitopes,

• define adjuvants and discuss their functions,

• explain the immunological variants of antibodies present in mammalian body,

• distinguish between isotype, idiotype and allotype antibodies,

• differentiate between polyclonal and monoclonal antibodies, and

• discuss the principles and applications of important immunological tools, and

Block Preparation Team

The presents volume (Volume I) comprises 2 blocks namely

Block 1: Introduction to Immunology

Unit 1 “Overview of the Immune System” gives an insight of historical perspective of

• trace the course of development of the field of immunology,

• define Toll like Receptors,

• discuss the functions of NK cells,

• differentiate between humoral and cell-mediated immunity,

• compare and differentiate functions executed by primary and secondary lymphoid

• discuss the process of generation, regulation and functions of immune cells,

• explain mechanism of immune responses, and

• discuss the properties of Antigen Recognized by the B and T cells,

The Innate Immune System Bacteria

The Adaptive Immune System Protozoa

Humoral Immunity Helminths or Parasitic Worms

Cell Mediated Immune 1.7 Host-Pathogen Interaction

Exogenous Antigen Processing Mechanisms used by Pathogens

 trace the course of development of the field of immunology,

 explain an overview of the immune system,

 explain the basic causes of autoimmunity,

 list the postulates of Clonal Selection theory,

 explain basic terms like pathogenicity and transmission,

 list the various classes of human pathogens, and

 give examples of major pathogenic diseases.

1.2 HISTORICAL PERSPECTIVE OF

• Thucydides in 430BC while describing a plague in Athens introduced the

• Lady Mary Wortley Montagu observed in 1718 the advantages of

• Edward Jenner, an English physician in 1789 went on to improve this

• The next discovery made by Louis Pasteur was a fortunate happening.

• The first vaccine was administered by Pasteur in 1885 to a young boy

• The first insight to the working mechanism of immunity was established

• Elie Metchnikoff observed that certain cells which he called phagocytes

• The lymphocyte was identified in 1950s as an important element of

• Bruce Glick demonstrated via his experiment on chickens that cell

a) Variolation was first performed by …………………. on her children.

b) ……………………. observed the phenomenon of phagocytosis for the