IMMUNOLOGY AND SEROLOGY_PRELIM

HUMAN IMMUNE SYSTEM_REVIEW OF IMMUNITY d. Innate immune response

Human Immune System _Overview 7. Differentiated forms of B lymphocytes

PRE TEST a. Mast cells

b. Plasma cells
1. A component of the innate defense system serving c. Macrophage
as the external protective shield of the body against d. Lymphoblast
colonizing microbes.
8. Which of the following cells are capable of
a. Intact skin recognizing foreign antigens.
b. Mucous membrane
c. Phagocytes a. B cells
d. Normal flora organisms b. Dendritic cells
c. Langerhan cells
2. They are innate lymphoid cells with cytokine d. Macrophage
producing capacity. e. All of the above
a. Natural killer cells TRUE or FALSE
b. Macrophage
c. T helper cells 9. Active acquired immunity is conferred to an
d. B cells individual who have recovered from an illness or
disease.
3. It is both a lymphoid and endocrine organ important
in the development of functional T lymphocytes. 10. Passice immunity provides lifelong protection from
a disease.
a. Bone marrow
b. Spleen Learning Outcome
c. Thymus  Discuss the basic structures and functions of
d. Lymph nodes the tissues, organs and cells comprising the
immune system.
TRUE or FALSE  Describe the roles of the different organs,
tissues and cells in the development of immune
4. There is a gradual decrease in the size and
response.
secretory abilities of the thymus as one ages.  Define immunity
 Differentiate the characteristics of Natural and
5. The skin, respiratory and gastrointestinal tract are
Acquired Immunity
lined with epithelial barriers that contains dendritic  Discuss the components of the Natural and
cells that capture and deliver antigens into the Acquired Defense system and their mechanism
lymphatics. of action.

6. T lymphocytes are involved in what type of immune Immune System

response?
- Refers to the lymphatic system - considered as
a. Cell mediated immune response one-way system to the heart
b. Humural immune response - Network of cells, tissues and organs that
provides the body mechanisms to resist
c. Both cell mediated and humoral immune
infection amd disease.
response - Root of the study of Immunology

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- Considered as return system

Oveview of the Components of Human Immune

System

Human Immune System – Functional

Compartments

A. Stem Cell / Generative Compartment

- Bone Marrow
B. Primary / Central Lymphoid
- Thymus – lymphocytes will mature
- Bone marrow
C. Secondary / Peripheral Lymphoid – where
mature lymphocyte will reside
- Encapsulated
- Unencapsulated
- Organs e,g. (cutaenous IS, MALT)

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Primary Lymphoid Organ – Thymus – this is where

T cells develop their identity

- At birth: 30 g, puberty: 35g

- Site of development of functional Tcells
 Cortex – immature thymocytes, surface
antigens are acquired
 Medulla – mature Tcells and APC- Antigen
Presenting Cells

Bone Marrow / Myeloid Tissue – largest tissue in the

body; weight 1300 - 1500

- Center for antigen-independent lymphoiesis

- Birthplace of all hemapoietic stem cells
- Precursor cells proliferate and mature as
induced by cytokines. Ex. C-kit, IL3, IL7, CSFs,
Fit-3 ligand

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- Naïve or resting lymphocytes die w/in a few

days after leaving the primary lymphoid organs
unless activated by foreign Ag

Lymph Nodes

- Superficial groups
Thymus  Cervical
 Axillary
- H&E stain, Magnification 100x respectively.  Inguinal
Note the detail of the thymic corpuscle, - Deep groups
chowing the concentrically arranged acidophilic  Tracheobronchial
layers and the relationship of these structures  Aortic
to the medullary region  Iliac
- Drainage
Thymic corpuscles
 Superior R ¼ of body: R
- Release cytokines that targets on dendritic cell lymphatic duct (green)*
activity  The rest: thoracic duct*

Secondary Lymphoid Organs Lymph Node

- Spleen, lymph node, tonsils, appendix, peyer’s  Filters the lymph of impurites
 Provides an environment where immune cells
patches, MALTs
can interact with foreign agents
- Where reproduction of lymphocytes occur (Ag
dependent)

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- Cortex – B cell area

 Primary follicle – resting /
naïve cells
 Secondary follicle – primed B
cells
- Paracortex – T cell area
- Medullary Cord – Plasma cells

Lymphocyte Recirculation

- Movement of lymphocytes from the blood to the

- Refers to the migration of lymphocytes from the
lymphoid organs and back to the blood.
central lymphoid organ to the secondary
Lymphocyte honning and recirculation
lymphoid organs or tissues, via the
bloodstream, in order to perform their functions.
- Cells continuously recirculate throughout the
body to seek out, recognize foreign agents

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- Mechanism: Migration of immune cells - Large discriminating filter

involves interaction of multiple adhesion - Pitting and culling
molecules preesnt on cell surfaces with their - Splenic tissue can be divided:
ligans on endothelial cells to permit traffic from o Red pulp- destroys old RBCs
the bloodstream into the lymphoid tissues and o White pulp- contains the lymphoid
inflammatory sites tissue

 Periarteriolar Lymphoid Sheath (PALS):

T cells area
 Primary follicles: B cells
 Marginal zones: dendritic cells; plasma
cells

- Protects the body from foreign antigens in the

blood; remove effete RBC, immune complexes,
opsonized microbe from the circulation; initiate
interaction of immune cells to blood borne
Spleen antigens.
- Largest 2o lymphoid organ
- 12 cm length, 150 g weight (adult)
- Upper-left quadrant of the abdomen

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Tonsils

- Simplest lymphoid tissue: swellings of mucosa,

form a circle

Other Secondary Organs

 T and B cells are segregated and perform

specialized fxn
 MALT: GIT, Respiratory, Urogenitals
: MO and lymphocytes
 Peyer’s patches: specialized MALT
 Tonsils: pathogens entering the respiratory
and alimentary tracts
 Appendix
 CALT: epidermis plus lymphocytes

Parts of the intestine are so densely packed with

MALT (mucosa-associated lymphoid tissue) that they
are considered lymphoid organs

- Aggregated lymphoid nodules (Peyer’s

 Palantine (usual tonsillitis)
Patches)
 Ligual (tounge)
o About 40 follicles, 1 cm wide
 Pharyngeal (“adenoids”)
o Distal small intestine (ileum)
 Tubal
- Appendix

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Cells of the Immune System

Professional Phagocytes
Neutrophil
- 3-5 lobes
Monocyte
- Bean-shaped
- Has granules
- Grainy cytoplasm
Macrophage
- Monocyte that
escaped from
blood to tissue

- attractant

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- elimination of Antigen-
antibody complexes

Dendritic Cells

- Professional antigen presenting cells

- Most potent phagocyte

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Natural Killer Cells Important Receptors:

- Third Population Cells / Large Granular  Inhibitory Receptors

Lymphocytes 1. KIR – Killer Inhibitory Receptors –
- Primitive T Cytotoxic Cells prevent killing of self cells
- With tumoricidal and anti-viral activity 2. CD94/NKG2A – binds to MHC Class I
- MHC – unrestricted cytolysis or Cytotoxic  Activation Receptors
reaction 1. CD16
- Antibody Dependent Cell Mediated Cytoxicity 2. NKG2D
(ADCC)  Both receptors bind to diseased
and cancer cells – cells
producing stress proteins

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 Ontogeny of B Cells

 Ontogeny of T Cells

Antibody Dependent Cell Mediated Cytotoxicity

T and B Lymphocytes

IMMUNITY

Ontogeny of T and B Cells Major Pillars of Immunity

 Innate Immune System

o Also called natural immunity
o Non specific, In-born immunity system
o First step in host defense against infection –
first line; second line
 Adaptive Immune System
o Acquired immunity system

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o Complex system that mounts a specific - Ability to resist infection by means of normally
immune response towards foreign agent present body functions
(antigen) - Same response for all pathogens
- No prior exposure is required
- Response does not change upon repeated exposure
- Influence by factors llike nutrients, age, fatigue,
stress and genetic determinants
- External defense mechanism-keep microorganism
from entering the body
- Internal defense mechanism - both cellular and
humoral factors

Innate Immune System

- includes physical, chemical, and cellular barriers

- physical barriers eg. skin and mucous membranes
- chemical barriers eg. stomach acidity, secreted
antimicrobial peptides
- cellular barriers eg. macrophages, neutrophils
- innate immune response activation occurs within
minutes of pathogen recognition

External Defense System

Lines of Defense of the Immune System

- structural barriers that prevent microorganisms from

entering the body
- intact skin
- mucous membranes
- secretions
Innate Immunity o Examples of secretions:
 actic acid (sweat)
Natural Immunity
 fatty acids (sebaceous glands)
- Also called innate immunity  lysozyme (saliva, tears): attacks
gram + bacteria
- Non specific/non-adaptive
 acid pH (stomach)

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 anti-fungal peptides called alpha-

defensins (intestinal tract)
 anti-microbial peptides called beta-
defensins (respiratory, urogenital
tract)
 surfactant-A and -D proteins
opsonize pathogens for enhanced
phagocytosis (lung)
 lactic acid (vagina)

Epithelial Defense Mechanisms

Second-Line Defenses
- flushing action of urine
(also acid pH) - If a pathogen is able to get past the body’s first line
- motion of the cilia of defense, and an infection starts, the body can rely
- presence of normal flora on its second line of defense.
(competitive exclusion)
Internal Defense System

- Cells and soluble factors play essential parts

- Recognize moelcules
o CHO mannose
- WBCs, phagocytosis, inflammation
- Acute phase reactants: enhances phagocytosis

First-Line Defenses

- the body’s first line of defense against pathogens

uses mostly physical and chemical barriers

External Barriers to Infection

Physical Barriers to Infection

 Skin – Stratum corneum – provides a hostile

environment unfavourable for bacterial colonization Internal Barriers to Infection
and growth.

- commensal organisms

Acute Phase Reactants

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- Normal serum constituents

- Increase rapidly due to infection, trauma, injury
- egs:
o C-RP -MBP
o serum amyloid A
o fibrinogen
o complement components
o haptoglobin
o alpha1
o antitrypsin
o ceruloplasmin o Cellular localization:
 Lysosomal localization (i.e.
subcellular) of TLR-3 and TLR7-9
 TLR-3 and 7-9 recognize
viral/bacterial nucleic acids
 lysosomal expression isolates
pathogen nucleic acid recognition
away from potential cross-reaction
with host mammalian nucleic acid
motifs

Inflammatory Cytokines
Innate Immune Receptors
These cytokines are critical for host defense.
- Innate immune receptors are not clonally distributed
Egs:
- Binding of receptors results in rapid response
- Innate immune receptors mediate three functions:  TNFa activates macrophage and PMN phagocytosis
o phagocytic receptors to stimulate pathogen and killing
uptake  IFNab activates anti-viral mechanisms
o chemotactic receptors that guide phagocytes  IL-1 stimulates inflammation and fever
to site of infection
o stimulate production of effector molecules
and cytokines that induce innate responses
and also influence downstream adaptive
immune response

Toll-Like Receptors (TLRs)

Activated macrophages secrete proteins that drive innate

response

 Cytokines

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-
- induce response by binding to specific
receptors
- can function in autocrine or paracrine
manner
- cytokines (and their receptors) are clustered
according to structural similarities
- critical cytokines secreted by macrophages
following activation include TNFa, IL-1,
IL-6, IL-12 to stimulate inflammation and
phagocytosis/killing
 Chemokines
- diverse family of chemotactic cytokines,
induce directed chemotaxis of cells
- all related in amino acid structure
- certain chemokines induce cell activation in
addition to cell recruitment
- promiscuous in receptor usage, each can
bind more than one receptor
- likewise, receptors are promiscuous
- Infection induces the release of various
chemokines
- Theses substances bind specific and
sometimes shared receptors to recruit
various types of immune cells to the site of
infection Inflammation

- Cardinal Signs of Inflammation

 Rubor (redness)
 Calor (increased heat)
 Tumor (swelling)
 Dolor (pain)
 Functio laesa (loss of function)

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Clinical symptoms of inflammation:

1. Increased vascular diameter, increased

blood flow (heat, redness)
2. Activation of vascular endothelium to
express adhesion molecules, increases
leukocyte binding
3. PMNs are first cell type recruited to site,
followed later by monocytes
4. Increased vascular permeability results in
local swelling and pain

- Principal Components:
 Vasolidation leading to an increase in
blood flow to the infected area.
Microvascular coagulation helps prevent pathogen
 Increased capillary permeability
spread into bloodstream (physical barrier)
 Diapedesis of leukocyutes

What is the importance of these inflammatory

responses mounted by inate defences against the
infecting agent?

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Summary and Review of Innate Immune Responses

In summary…

Innate Immunity

Characteristics:

- rapid
- does not generate immunologic memory
- dependent upon germline encoded receptors recognizing structures common to many pathogens

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from person who was previously

immunized by the foreign antigen.
Adaptive Immunity  Both Active and Passive immunity may be
developed by natural or artifical means.
Adapative Immune System

- also known as ACQUIRED IMMUNITY

 specific protection acquired from
infection or intentional immunization
- made up of highly specialized cells that
expressed unique antigen receptors to
Active vs. Passive Adaptive I.
recognize and mount a destructive response
against foreign agent.
- Third Line of Defense of the immune system

Innate vs Adaptive Immune System

Major Arms of Adaptive Immune System

Forms of Adaptive I. Active and Passive

 Active Adaptive Immunity

- Acquired or developed in an individual
on exposure to a foreign body. This
individual’ immune system is involved in
the production of immune factors (e.g.
antibodies and sensitized lymphocytes) POST TEST
 Passice Adaptive Immunity
TRUE OR FALSE
- in contrast to active immunity, the
individual receives the immune factors

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1. The isolation of lymphiod stem cells and their 9. Which immune cell is engaged in ADCC?
descendant from the general circulation is through the
blood thymus barrier. 10. (Identify) This granulocyte is the major immune cell
of adaptive immunity.
2. In th elymph nodes, resting or naïve T and B cells
are able to recognize and respond to foreign antigens
brought and collected by the from peripheral The human immune system is essentially the
tissues. body's defense mechanism against infection and other
a. Blood pathogens. It is made up of a network of cells, organs,
b. Plasma and tissues from the body. The bone marrow, thymus,
c. Lymph spleen, and lymph nodes are among the organs
d. All of the above involved. The immune system is made up of cells such
as professional phagocytes, dendritic cells, natural
TRUE OF FALSE killer cells, and T and B lymphocytes. Furthermore, the
innate immunity system, also known as the natural
3. The anatomci organization of the componentys of immunity system, and the adaptive immune system
the immune system is critical in the rapid delivery of are the two major pillars of immunity.
innate immune cells to site of infection as well as
efficient adaptive response to antigen.

4. Which of the following factors is not a component of

the internal innate defense system?

a. Complement
b. Cathelicidin
c. Ceramides
d. CRP

5. The is the first line of the innate defense

system as it serves as the protective shield of the body
against colonizing pathogens.

6. A neonate receiving BCG immunization will

developed what form of adaptive immunity?

7. Lymphoid follicles having germinal centers would

contain what type of lymphocytes?

a. Naïve B cells
b. Resting T lymphocytes
c. Activated B cells
d. Primed T cells

8. (Identify) Collectively, this refers to the immune

components associated with the mucosal lining of the
bronchus and the gastrointestinal tract.

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