Basic Immunology

Acknowledgements

 Addis Ababa University

 Jimma University
 Hawassa University
 Haramaya University
 University of Gondor
 American Society for clinical Pathology
 Center for Disease Control and Prevention Ethiopia
 Chapter 1

An Overview of the Immune System

 Learning Objectives for Immunology
Overview

Upon completion of this lecture and exercises the

student will be able to:
 Define the terms immunity, immunology
 Describe major historical events in the development of
immunology
 Differentiate innate and adaptive immunity in terms of
components and type of immune response.
 Explain the major defenses of innate immunity
 Describe the mechanisms used by the body to defend
itself in an innate response.
 Outline

1.1. Terminologies in immunology

1.2. History of immunology

1.3. The immune system

1.4. Natural immune system

1.5. Adaptive immune system

1.1. Definition of terms

 Immunology
 The study of immune system or immunity
 the study of all aspects of host defense against
infection and of adverse consequences of immune
responses.
 The study of the physiological mechanisms which
enable the body to recognize materials as foreign and
to neutralize, metabolize or eliminate them without
injury to the host tissue.
 cont…

 Immunity
 State of protection from infectious diseases

Immune system
 A remarkably versatile defense system that has evolved
to protect animals from invading pathogenic
microorganisms and cancer.
 It is able to generate an enormous variety of cells and
molecules capable of specifically recognizing and
eliminating an apparently limitless variety of foreign
invaders.
1.2. History of immunology

 Its principles among the earliest written observations;

 Individuals recovering from certain disease rarely
contracted that same disease again.
 observation promoted deliberate attempts to induce
immunity
 Athens plague as of Thucydides in 430BC (recovered
people only nurse sick one)
 cont…
 Chinese(1500A.D) custom of inhaling crusts from
smallpox lesions to prevent development of small pox in
later life.
 Injecting materials from crusts or fluid from smallpox
blisters (“variolation”), used through out the eastern
world, in 1718 was introduced into western medicine by
British ambassador’s wife, to Turkey, had her children so
treated.
 Note- The virus used could be transmitted =>

protection by variolation was hazardous to the

community at large!!
 cont…

 In 1798, Jenner’s work on vaccination, describing a

related, yet safe procedure.
 Noted people, who had cow pox, were spared in
small pox epidemics,
 inoculated boy with pus from milk maid with cow pox,
and
 re-inoculated same boy with infectious pus from a
patient in the active small pox.
 No disease state followed these inoculations, and
experiment was repeated several times with great
success!
 cont…

Louis Pasteur- demonstrating

that it was possible to
attenuate, or weaken, a
pathogen and administer the
attenuated strain as a vaccine.
In 1885, Pasteur administered
his first vaccine to a human, a
young boy who had been
bitten repeatedly by a rabid
dog

Wood engraving of Louis Pasteur watching Joseph Meister receive the rabies vaccine.
[From Harper’s Weekly 29:836; courtesy of the National Library of Medicine.]
 cont…
 Jenner`s provided first clear evidence that active
immunization could be used safely to prevent an
infectious disease.

 Almost 70 Years later, Pasteur - introduced

pasteurization also
 Recognized and exploited the general principle
underlying vaccination

 At about 1900,
 Role of phagocytes and cellular immunity were
elucidated
 cont…

 Killed vaccines were introduced

 Complement was described
 In 20th century,
 Acquired immunity resulted from both cellular and
humoral elements were demonstrated.
 Opsonization was described
 The term antigen came in to regular use
 cont…
Noble prize winners for immunologic research
 1901 Emil von Behring, Serum antitoxins
 1905 Robert Koch, Cellular immunity to tuberculosis
 1908 Elie Metchnikoff, Role of phagocytosis
 1908 Paul Ehrlich, antitoxins in immunity
 1913 Charles Richet, Anaphylaxis
 1919 Jules Border, Complement-mediated bacteriolysis
 1930 Karl Landsteiner, Discovery of human blood groups
 cont…
 1951 Max Theiler, Development of yellow fever vaccine
 1957 Daniel Bovet ,Antihistamines
 1960 F. Macfarlane Burnet and Peter Medawar,
Discovery of acquired immunological tolerance
 1972 Rodney R. Porter and Gerald M. Edelman,
Chemical structure of antibodies
 1977 Rosalyn R. Yalow, Development of
radioimmunoassay
 1980 George Snell, Jean Daussct and Baruj Benacerraf
Major histocompatibility complex
 cont…
 1984 Cesar Milstein and Georges E. Köhler, Monoclonal
antibody
 1984 Niels K. Jerne, Immune regulatory theories
 1987 Susumu Tonegawa, Gene rearrangement in
antibody production
 1991 E. Donnall Thomas and Joseph Murray
Transplantation immunology
 1996 Peter C. Doherty, Role of major histocompatibility
complex
 1996 Rolf M. Zinkernagel, in antigen recognition by by T
cells
 1.3. The immune system

Immune System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Humoral

Cell-Mediated
Components Components (Ab)
 1.3. The immune system
Overview of the Immune System
1.4 The Innate immunity

Natural immune system (Innate Immunity)

 Non – specific
 First line of defense
 Repeated exposure - no augmentation
 Components
 Biochemical
 Physical
 Cells
 cont…

1. Components Lysozymes
a. Biochemical
Mucus
 enzymes, C’, etc.
 secretions Cilia: trachea
 pH Sebaceous glands
b. Physical
 skin Skin
 cilia
Acid in
c. Cells stomach
 Phagocytes, NK
Commensal
2. Example
organisms in
a. Burn response gut & vagina
Spermine in semen
cont…
 cont…

 Overall non-specific reaction of body to injury or invasion

– starts immediately with infection or trauma
 Reactants may initiate, expand, or sustain the
response
 Can be acute (short duration) or become chronic
(prolonged duration)
 Has 4 cardinal signs: heat, pain, redness, loss of
function resulting from:
 cont…
 Increased blood and plasma flow to the area
 Increased capillary permeability by retraction of
endothelial cells
 mediated by vaso active agents such as histamine
and prostaglandins.
 derived from injured cells and later from cells that
infiltrate the area.
 Migration of leucocytes, particularly Neutrophils and
macrophages, from the capillaries to the site of injury is
due to a process called chemotaxis.
 cont…
 Migration of white cells, especially early migration of
neutraphils then macrophages to the area
 Increased release of mediators such as histamine
from damaged mast cells – furthering capillary
dilation
 Increased concentration of acute phase reactants
that can amplify and/or control the response
 Complement – a series of enzymes normally
circulating in an inactive form may be activated
resulting in lysis or enhanced phagocytosis of
cells
 cont…
1.4.1 External Innate Defense Systems
Prevent entrance:
 Structural barriers – effective with most
microorganisms
 Skin - epidermis = layers of tightly packed

epithelial cells. Outer layer is dead cells and

keratin, waterproofing protein
 Inner layer skin - dermis = blood vessels, hair

follicles, sweat glands, and sebaceous glands

that produce an oily secretion called sebum
 Cilia and cough reflex – helps expel microbe

containing mucous
 Sneeze
 cont…
1.4.1 External Innate Defense Systems
Mucus - conjunctivae, alimentary, respiratory, and urogenital
tracts
• saliva, tears, and mucous secretions wash away
invaders and contain antibacterial or antiviral
substances.
• acidity (pH 5.6) of sweat, sebaceous glands, vagina
(pH 5) and stomach (pH 1) – unfriendly to many
microorganisms
 enzymes present in the skin and stomach, tears
Normal flora - out compete pathogens for attachment sites
on the epithelial cell surface and for necessary nutrients.
 cont…
1.4.2 Internal Innate Defense System
To prevent expansion of penetration
 Recognize carbohydrates not normally present on cells
such as mannose
 May cause nonspecific activation of white cells
 Phagocytosis – by neutraphils, eosinophils,
basophils, or macrophages, mast cells, and dendritic
cells
 Clotting mechanism which entraps organisms in fibrin
clots
 Complement System can lyse cells or enhance
phagocytosis
 cont…

Physiologic Barriers
 Soluble factors contribute to innate immunity, they are
collectively known as acute phase reactants.
 Normal serum components, non-specific responders to
inflammation
 Increase because of infection, injury, trauma
 Produced mostly by liver in response to inflammation
and cytokine stimulation
 Cytokines: IL-1, IL-6 and TNF alpha which are produced by
macrophages and monocytes at inflammatory site are activators
 cont…
 Acute phase reactants are chemically varied and include:
 C-reactive protein,
 serum amyloid A,
 mannose binding protein,
 alpha-1 anti-trypsin,
 haptoglobulin,

 fibrinogen,

 ceruloplasmin,

 alpha-1 acid glycoprotein

 Complement
 cont…
 Complement – a series of enzymes normally circulating
in an inactive form
 May be activated by the classical or alternate
pathways
 Can result in lysis or enhanced phagocytosis of cells

 Lysozyme, a hydrolytic enzyme in mucous secretions

and in tears, can cleave the peptidoglycan layer of
bacterial cell wall.

 Interferon, proteins produced by virus-infected cells.

Has many functions including ability to bind to nearby
cells and induce a generalized antiviral state.
 cont…
C-Reactive Protein
 Normally trace levels in serum

 Early acute inflammation indicator:

 increases within 4-6 hrs of infection or trauma
 100 to 1000 fold increase serum concentration
 concentration drops rapidly in serum when stimulus
removed
 Enhances opsonization, agglutination,
precipitation, and classical pathway complement
activation – enhances removal of irritant
 cont…
Phagocytosis
 Phagocytic cells Chemotaxins such as
 Complement components
 Coagulation cascade proteins
 Bacterial and viral products
 Attract phagocytic cells including:
 Mast cell, lymphocyte, macrophage, neutrophil
products
 Physical contact between phagocytic cell and foreign
object results in
 Formation of phagosome
 Formation of phagolysosome
 Digestion
 Release of debris
 cont…

 Phagocytosis
 Is a form of endocytosis.
 Important body defense mechanism is process in which
specialized cells engulf and destroy foreign particles
such as microorganisms or damaged cells.
 Macrophages and segmented Neutrophiils are the most
important phagocytic cells.
 cont…

 Can be divided in to several stages:

 chemotaxis – attraction of leukocytes or other cells by
chemicals
 Movement of neutraphils is influenced by chemotaxins –
chemical messangers
 Complement, proteins from coagulation,
 Products from bacteria and viruses,
 Secretions from mast cells, lymphocytes, macrophages,
and other neutraphils
 cont…

 Phagocytosis ...
 Adherence – binding of organism to the surface of
phagocytic cell.
 Engulfment:- is the injestion of m/os and formation of
phagosomes.
 Digestion – after the foreign particle or m/os is
ingested, cytoplasm lysosome fuse with phagosome
The enzymes of lysosome then contribute to microbial
killing and lysis.
 cont…

Phagocytosis ...

Source: Kuby immunology 2007, 5th ed

 1.5. The adaptive immune system

Immune System

Innate Adaptive
(Nonspecific) (Specific)

Cellular Humoral Humoral

Cell-Mediated
Components Components (Ab)
1.5. The adaptive immune system
1.5. The adaptive immune system

1.5. Adaptive Immunity

 Specific
 Second line of defense
 Repeated exposure - augmented – memory
 Faster response
 More vigorous response
 Longer lasting response
 Anamnestic

Components
Classic Immune System
 Cells (Cell mediated) =CMI
 Soluble Factors (Humoral immunity) = HI
1.5. The adaptive immune system
 Capable of recognizing and selectively eliminating
specific foreign microorganisms and molecules(i.e.,
foreign antigens).
 Unlike innate immune responses, adaptive immune
responses are reactions to specific antigenic challenges
 Different populations of lymphocytes and their products
are the major actors together with accessory cells –
Antigen presenting cells (APCs)
 Cardinal features are :
 Specificity

 Diversity , Memory,
1.5. The adaptive immune system

Cardinal Features of adaptive Immune Responses

 Specificity –
 specific for distinct antigen, and
 for different structural components of a single
complex protein, polysaccharide, or other
macromolecules.
 Portions of such antigens recognized by individual
lymphocytes are called determinants or epitopes.
 This fine specificity exists because individual
lymphocyte express membrane receptors able to
distinguish subtle (slight) differences in structure
between distinct antigens.
 1.5. The adaptive immune system

 Diversity- total number of antigenic specificities of the

lymphocytes in an individual, called the lymphocyte
repertoire, is extremely large.
 estimated mammalian immune system can discriminate
109 to 1011 distinct antigenic date ruminants.
 This property of the lymphocyte repertoire is called
diversity. It is the result of variability in the structures of
antigen- binding sites of lymphocyte receptors for
antigens.
1.5. The adaptive immune system

 Memory- Exposure of the immune system to foreign

antigen:
 enhances its ability to respond again to that antigen.
 Responses to second and subsequent exposure to
the same antigen, called secondary immune
responses, are usually more rapid and larger than the
first or primary immune response.
1.5. The adaptive immune system

 An effective immune response involves three major

groups of cells: Cellular Immunity (T lymphocytes),
Humoral Immunity (B cells), and Accessory cells (antigen-
presenting cells).
 The two major populations of lymphocytes—B
lymphocytes (B cells) of Humoral immunity and T
lymphocytes (T cells) of Cellular Immunity provide us
with our specific adaptive immunity
1.5. The adaptive immune system

 Specialization –the immune system responds in distinct

and special ways to different microbes, maximizing the
efficiency of antimicrobial defense mechanisms. Thus,
humoral immunity and cell mediated immunity are elicited
by different classes of microbes or by the same microbe
at different stages of infection (extra cellular & intra
cellular)
 Self –limitation- All normal immune responses returning
the immune system to its resting or basal state with time
after antigen stimulations, process called homeostasis.
Summary of innate and adaptive immunity

Comparison of Innate and Adaptive Immunity

Innate Immunity Adaptive Immunity

• No time lag • A lag period

• Not antigen specific • Antigen specific

• No memory • Development
of memory
 Summary of innate and adaptive immunity

Adaptive and Innate - Interactions

Infectious Innate Immunity No
Exposure holds Disease

Innate Immunity
Fails
Adaptive Immunity
Specific memory

Disease

Adaptive Second Infectious

Recovery Exposure
Immune system
Same organism
Summary of innate and adaptive immunity

This is the end of chapter I

and

The next chapter will be:

The cells and organs of immune system

Next
Review questions

1. Define the term immunity and immunology?

2. Describe the historical events of immunology and its

development.

3. What is the difference between innate and adaptive

immunity in terms of components and type of immune
response.

4. Explain major defense mechanism of innate immunity

and adaptive immune system
 Reference
1. Kuby; Goldsby et. al. Immunology. 2007 (5th ed)

2. Tizard. Immunology an introduction,4th edition ,Saunders publishing,1994

3. Naville J. Bryant Laboratory Immunology and Serology 3rd edition.

Serological services Ltd.Toronto,Ontario,Canada,1992

4. Abul K. Abbas and Andrew H. Lichtman. Cellular And Molecular

Immunology 2008, 5th edition

5. Mary T. Keogan, Eleanor M. Wallace and Paula O’Leary Concise clinical

immunology for health professionals , 2006

6. Ivan M. Roitt and Peter J. Delves Essential immunology 2001, 3rd ed

7. Reginald Gorczynski and Jacqueline Stanley, Clinical immunology 1990.