Immunity(Lectures)
D.Wafaa Alwazni
IMMUNOLOGY
 Definition
It is the Science which deals with Immunity. Immunity is a condition of being immune
(resistant) to an infection.
Immunology is related to the following sciences:
-
Microbiology
Biochemistry
Genetics
Medicine
Others
 Branches of Immunology
1. Serology: the study of antigen – antibody in vitro, use of serum in the diagnosis of
infection
2. Immunochemistry: the chemistry of immunity & it deals with the chemical analysis of
antibodies molecules & the chemical structures of antigen.
3. Immunobiology: the reaction of biologic phenomena to immunity & study of cellular
behavior of animal & man, when foreign material introduced to the body. Ex:
Hypersensitivity, Auto immune disease, tolerance.
4. Immunogenetics: deals with the inheritance of antigenic characters related to immune
response or is a science that investigates the genetic control of Ab diversity,
transplantation reaction & graft rejection.
5. Immunopathology: is a science that deals with the immunologic causes of human &
animal diseases like graft rejection & tumor host relation.
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 Compartment of immune system :Three basic compartment of the immune system have been recognized, these are:
1.
2.
3.
4.
Hematopoietic system (HS)
Lymphoid system (LS)
Reticuloendotheloid system (RES)
Secretory system (SS)
First\\ Hematopoietic System (Cells of the Immune System)
There are 3 groups of blood cells involved in the immune response which totally arise
from stem cell or cells residing principally in the bone marrow . these groups include
1.
Granulocytes:
It is composed of 3 distinct cell types which distinguished by the structure both nuclear
& cytoplasmic components
a-Neutrophils:
They are generally the first WBC to
localize at the site of a foreign invasion & makes these functions:
*Phagocyte activity
*Margination phenomenon
which occurs in 2 phases:
 The initial weak binding is mediated by selectins on the neutrophil
 The integrins mediate tight binding to the endothelial surface &
later facilitate emigration & migration of neutrophil through the
adjacent tissue by ability to bind to fibronectine & other component
of the extra cellular matrix .
The emigrated neutrophil passes between endothelial cells, with their active
collaboration, to migrate out of the vessel into the adjacent tissue. The neutrophil
then travel by amoeboid up the concentration gradient of chemo-tactic factors until
they arrive to the injury or infection.
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*Contain important material in granule: as show in this table
MATERIAL
AZAROPHILIC
GRANULES
SPECIFIC GRANULES
Microbiocidal
proteins
Lysozyme
Lysozyme
Protease
Collagenase
Collagenase
Acid hydrolyses
Lipases
Lactoferrin (inhibit bacterial growth
by chelating iron)
Other proteins
b- Basophiles: have some immunological
1. Phagocytes poor
2. participate in hypersensitivity as mast cell
3. involved in parasite immunity
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function:
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c-Eosinophils: Its immunological functions:
1. Phagocytic less active
2. Associated with allergic reaction
3. Play a role in containment of parasitic infection.
2- Monocytes :
The blood monocytes migrate in to peripheral tissue where they enlarge & differentiate
into macrophages or histiocytes and named according to organ found in it such as :
( In liver
in spleen
Kupffer , in kidney
Sinusadal , in brain
mesangid , in lung
Alveolar ,
Microglial , in bone
Osteoblast )
The function of monocytes:
1. phagocytic
2. Lysis of tumor cells
3. produce IL – 1
The function of Macrophage:
1.
2.
3.
4.
5.
6.
Phagocytic
Secretors complement component
present Ag to lymphocyte (T-cells)
Lysis tumor cell
Activate lymphocyte
Production certain lymphokines (IL-1)
3.Lymphocytes:
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They are the most important cells involved in the immune response, & posses most of
the properties that make the immune mechanism in higher vertebrates unique among
biological systems.
4.Mast Cells:
They play a very important role in allergic reaction in most species..
Properties of 3 major human cells linkage involved in host defense
CHARACTERISTIC
N
M
L
Primary effectors function
Phagocytosis
phagocytosis
varies
Cytoplasmic granules
Many
Moderate
No
Can synthesize new membrane
or secretory proteins
No
yes
yes
Principle normal location
Blood marrow
All tissue
Lymphoid tissue
Antigen presentation
No
yes
yes
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Immunoregulatory cytokine
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No
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yes
yes
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 Ontogeny of blood cells :-
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Second\\ Lymphoid System (organs):A\\ Primary lymphoid organs
Second/ Lymphoid System (Organs)
A/ primary lymphoid organs
It consists of the Thymus gland which plays a central role in the cellular
immune system& bone marrow which represent a haemolymphoid
organ. i.e.: It is the site where blood cells are formed as well as
lymphocytes matured. In non mammalian vertebrates, like birds (avis),
there is an organ which is called Bursa of fabricius (equivalent to the
bone marrow in mammals). Bone marrow or bursa of fabricius furnishes
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the immune system with B-lymphocytes which is actively producing cells
for Ab (Humeral immunity).
B\\ Secondary lymphoid organs
These organs are represented by spleen (It is the major site for removal
& destruction of dead RBC & it is an important organ of the immune
system) , peripheral lymph nodes(are small (less than 1cm) bean –
shaped structure, distributed throughout the entire body & linked
together by an equally extensive circulatory system of lymphatic vessels.
The principle functions of these nodes are in the entrapment of foreign
material in the lymph circulation & as a site for the antigen driven
maturation of lymphocytes) and Payer’s Patches which are lymph
aggregates located in the gut especially in the appendix & colon; they
contain:
 Fixed macrophages.
 Lymphocytes (B&T) cell, from gut associated lymphoid tissue GALT
(local immunity).
 Plasma cell IgA mainly.
 BALT: Bronchus Alveolar macrophage associated Lymphocytes
Tissue.
Third\\ Reticuloendothelial System
This system is represented by mononuclear leucocytes fixed in lungs,
liver, spleen & brain. These cells are embedded in reticular C.T &
vascular bands. Functionally, this system maybe responsible for local
immunity & may be known recorded as bronchus associated lymphoid
aggregate & gut associated lymphoid aggregates.
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Fourth\\ Secretory System
This system is mainly constituting plasma cells, or Ab producing
lymphocytes, on mucous membrane, saliva, ear wax. Immunoglobulin is
mainly IgA whether IgA1 or IgA2.
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The position of lymphoid organs
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 The architecture of the immune
system
The architecture of the immune system is multilayer with defenses on
several levels as shown in this figure
PATHOGEN
INNATE IMMUNE S.
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ADAPTIVE I. S.
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Physiological
condition
Cellular condition
Phagocytes' cell
Lymphocyte cell
 Types of immunity:
First\\ Natural
(Innate,
inherited)
immunity :
Natural (Innate, inherited) immunity: The type of immunity associated
with genetically controlled resistance.
a) Characteristic :
1. Non specific :- effective against many different kinds of infectious
2.
3.
4.
5.
agents.
Not affected by prior :- (earlier) contact with the infectious
agents.
Species specific :- one animal species contract a certain disease
with other species are resistant. e.g. human get mumps but dogs
don’t. Mammals get anthrax but birds do not.
Race differences :- human races seem to have differences in
susceptibility or resistance to certain disease. E.g. Black are more
resistant to diphtheria than whites.
Sex differences :- in certain strains of mice BA-LB/C females are
more resistant than males to certain infectious agents (Listeria
monocytogenes)
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6. Nutritional influence :- Resistance & susceptibility are affected by
nutritional status.
Low protein diet
Vitamin B1 B2 deficiency
Low C3
Low lymphocytes activity
7. Hormone relation :- hormone imbalance (insulin, diabetes) affect
susceptibility to infectious agent.
8. Age effect :- very young & very aged are more susceptible than
youth (less phagocytosis)
b) Mechanism of natural resistance :
1. Local or external (physical &cellular) includes : Skin :- anatomic barrier & contain antimicrobial secretion & it is
outer Keratein layer that shields the living cell & beneath it from a
hostile environmental.
 Eyes :- washing of tears & presence of lysozyme in tears.
 Respiratory tract : Mucous: it is a protective barrier, blocks adherence of
bacteriato epithelial cells.
 Ciliated epithelium: Coughing & sneezing
 Alveolar macrophage: phagocytosis
 Digestive tract : Lysozyme in saliva
 Stomach acidity
 Normal flora : which act in this ways:a- Competition for essential nutrients
b- Production of inhibitory substances
 Genitourinary tract :-
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



Washing of urine
Acidity of urine
Lysozyme in urine
Acidity of the tract
2. Internal factors or general :a) Humoral (potent biochemical substance)
1. Complement
2. B lysine
3. Interferon (one type of cytokines) :
α- interferon released by leucocytes.
β- Interferon released by fibroblast.
γ- Interferon released by T- cells.
4. Acute phase protein: proteins present in blood plasma & increase
during infection.
5. Lysozyme
b) Cellular
*Phagocytic cells (phagocytes) that include :
1. Amateur
- Epithelial
- Endothelial
- Fibroblast
2. Professional
- Macrophages
- Monocytes
- Polymorphs (Neutrophil) :
*Natural killer cells : are large lymphocyte cell that contain
cytoplasma granules where defined initially by their ability to kill
certain tumor cell & virus infiction cells in vitro.
 Their physiologic role are :
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 To be involved in host before against malignancies.
 Can be stimulated to produce a variety of cytokines &
may have complex regulatory role.
Development & tissue distribution of NK cells :
 Derive from bone marrow precursor & the require mat
for development of the NK cell lineage are clearly
distinct from those of T & B cell.
 NK cell make up about 15% of peripheral blood
lymphocytes & 3-4% of spleenic lymphocytes and are
also found in the lung interstate, the intestinal mucosa
and the liver but they are rare in the thymus & lymph
nodes.
Relationship between innate and adaptive immunity
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 The complement system
Complement : is a collective term use to designate a group of plasma
and cell membrane proteins that play a key role in the host defense
process
 pathway of Complement activation
The Complement cascade can be activated in 2 ways :
1. Classic Complement pathway
Under normal physiologic condition activation of this pathway is
initiated by antigen-antibody complex.
2. Alternative Complement pathway
(Properdin pathway) at does not have an absolute requirement for
antibody for activation.
 Activators of Complement
Can show in these tables:
IMMUNO
MICROORGANISMS
OTHERS
GLOBULIN
Viruses
Bacteria
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Others
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* Polyanions
po4 (DNA ,
Complexes
Murine
Lipid A ,
Classical
Containing
Retroviruses
Cardiolipin )
pathway
IgM,IgG1
Vesicular
IgG2 or
Stomatitis
IgG3
Virus
mycoplasma
* SO
(dextran
sulfate
heparin)
* Terminal
mannose
groups
Complexes
containing
IgG ,IgA
Alternative
pathway
or IgE
(lese efficial
than the
classical
Pathway)
Some virus
infected
cells
(e.g. ERV)
Many
Dextrose
sulfate
heterologus
Strain of Trypanosomes Erythrocytes
leishmania
G+ve &
many fungi Carbohydrate
G-ve
organism
(e.g. agarose)
 The major biological activates of the Complement system
:
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1. opsonization (coating) of m.o & immune complex so that they can be
recognized by cells expressing Complement receptor .
2. Lysis of target cells 2.
3. activation of phagocytes cells including macrophage & neutrophils
 Complement cascade :
Classical Pathway
MBLectin Pathway
Terminal Pathway
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Alternative Pathway
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 Acute phase proteins
APPs are plasma proteins that modify their concentration following
infection, inflammation, trauma or stress. APPs are mainly of hepatic
origin and their synthesis is regulated by pro-inflammatory cytokines,
hormone peptides that act as mediators between the damaged tissues
and the liver. some of which have antimicrobial affects for e.g. the
protein which binds to the so called C protein on the surface of
Pneumococci & thus promotes their destruction by the complement
cascade.
 Cytokines
Many interaction among cells of the immune system are controlled
by soluble mediators called Cytokines, which are diverse group of
intercellular signaling proteins that regulate not only local, system
immune & inflammatory responses but also wound healing,
hematopoiesis and many other biologic process.
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They are not produced by specialized glands but by different tissues
& individual cell. There for the cytokine produce by lymphocytes called
lymphokines but that produced by monocyte or macrophage called
monokines.
Each cytokines is secreted by particular cell types in response to
specific stimuli , produces a characteristic constellation of effects on the
growth, mobility, differentiation or function of its target cells for
example, the most important cell involved in allergy is the T lymphocyte,
and the control of migration, proliferation and differentiation of
activated T lymphocytes is co-ordinate by cytokines of various types. as
shown in this figure
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Second\\ Acquired or adaptive Immunity :
The immunity which a person develops during life time.
Characteristics :
a) Antigen (pathogen) specific
b) Depend on/or mediated by :
 Humoral substances. e.g. Antibodies or interferon
 Cellular in origin i.e. associated with activities of cells like
macrophages & T- lymphocyte.
A) Humeral or antibody mediated immunity is very efficient &
divided into :
1. Actively acquired immunity mean that a person synthesize his own
antibodies & which may be :
 Natural acquired : Result from infection
 Artificially acquired : result from immunization with :
- Artificial peptide
- Killed M.O
- Attenuated (viable but weak organism) produces mild infection
- Toxoid
- Gene cloning
2. Passively acquired Ι : mean that individual received their Ab from
some other individual either human or lower animal & which may be
:
 Natural : such as : Transplacental
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 Via colostrums (first milk) : This result in the coating of
infant digestive tract with antibodies secreted in first milk.
 Artificial : acquired of Ab through : Injection of hyper immune serum
 Injection of γ globulin
Comparison of active & passively acquired Immunity
Active
Passive
Source
Self
Some other human or lower
animal
Effect
High
Moderate or low
Administration of Ab by:
Method
Time to develop
1. Disease
2. Immunization
5-14 days
1. Material Hans placental
2. Injection of γ globuline
Immediate on injection
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Duration
Relatively long
Short days-several weeks
May be years
Ease of reactivate
Easy (booster)
Dangerous Anaphylaxis
Use
Prophylactic
Prophylactic & therapeutic
B) Cellular mediated immunity :
Or immune response is associated with activities of cell macrophages, Tcell & B cell This activation occurs as shown in these figures :-
 Activation of helper T cells
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 Activation of cytotoxic T cell
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 Activation of B cells to make antigen
The process by which T cell and B cells interact with Ag is summarized
in the diagram below:-(The immune system process can
summary in this figure):
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General distinctions between innate & adaptive
immunity :
Characteristic
 Receptor
 Distribution
 Kinetics
 Specificity
Innate
Adaptive
General encoded
Somatically engineered
Non clonal
Clonal
Rapid (minutes)
Slow (6 days)
Recognizes non-self through
(pattern recognition)
Recognizes (attired self) (in
order to survive lymphocytes
must recognize self, but not
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(exbacterial cell wall patterns)
 Effector cells
All cell of body potentially
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too strongly or too weakly)
Primarily lymphocytes and
macrophages
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The immune response
A)Characteristic of I.S. :
The immune system has at least 3 major functional properties that
distinguish it from all of the bodies other defenses:
1. Its extreme specificity:
The ability to recognize & distinguish among a vast number of different
target molecules & to respond (or not) to each of these individually.
2. The immune system discriminates between self & non self, so that it
normally coexists peacefully with all of the innumerable proteins & other
organic materials that make up the half but respond vigorously against
foreign substances, including cells or tissues from other people.
3. The immune system has memory that is the ability to be molded by
its experiences so that subsequent encounters with a foreign
pathogen provoke more rapid & more vigorous responses than
occurred at the initial encounter.
B)Types of immune response :
First\\ Non specific immune response:
A. Phagocytosis
B. Inflammation
A. Phagocytosis :
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 A process, by which microorganisms are engulfed, killed & digested.
Microphages: polymorphonuclear Nutrophil (PMN)
 Cells
Macrophages: Tissue phagocytes (Monocytes in blood &
macrophages inconnective tissue as Histiocytes).
 Phagocytic process :
 Include 4 steps:
1.
2.
3.
4.
Chemotaxis
Opsonization
Ingestion (engulfment)
Killing
(1) Chemotaxis :- Migration of phagocytic cells towards foreign – body
(micro organism) & accumulation at inflammatory loci in tissue.
Random
Motility
Directional
Example of Chemotaxins : Substances that promote directional motility
of phagocytes.
 Endogenous
- Fibrin fragment
- Collagen fragment
- Complement derivatives (C5a)
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- Chemokines (I L – 8)
- Platelet activating factor
 Exogenous
N – formylated oligopeptide in present of the amino terminals of
proteins from most type of micro organisms.
(2) Opsonization :- Coating of foreign body or (microgram) with
molecules that promote attachment of phagocytes to this body.
Specific : e.g. Antibodies
Opsonins
Non – specific : e.g. C3b of the alternative pathway.
(3) Ingestion (engulfment) :- Encirclement of foreign body by
cytoplasm of phagocytic cell & the formation of a vacuole called
phagosome.
 Engulfment of particle is characterized by the following
characteristics :
1) Increase oxygen uptake (respiratory burst) of phagocyte.
2) Increase of glycolysis or oxidation of glucose by hexose
monophosphate shunt (HMP – shunt)
3) Increase degranulation (removal of cytoplasmic granules)
 Steps of ingestion:
1) Formation of phagosome by encirclement of foreign body by
cytoplasm.
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2) Formation of phagolysosome by fusion of lysosomal granules
with phagosome.
(4) Killing :- Death of engulfed M.O.
Oxygen – dependent
Mechanisms of killing
Oxygen – independent
B. Inflammation :
Although lymphocytes & APCs are the key cells in all immune responses,
other types of cells may be recruited into the response.
For example cytokines or other products released by activated
lymphocytes & macrophages may :
1. Chemo attracts neutrophils or eosiniphils.
2. Stimulate proliferation of fibroblasts & endothelial cells
3. Cause mast cells & basophils to discharge other bioactive substances
into the local tissues.
These agents, as well as products of the complement cascade may lead
directly or indirectly to increased local vascular perfusion, capillary
permeability, accumulation of extra vascular fluid & pain.
In some instances, other enzymatic pathway such as the kinin, clotting &
fibrinolytic systems may also become activated.
Second\\ Specific immune response:
When an antigen enter the body *Encounters a specialized class of
cells called (A.P.Cs) which capture a minute amount of the antigen &
display it in a form that can be recognized by Ag – specific helper T
lymphocyte, this step called Ag processing & presentation,
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*
T cells only recognize immunogens that are bound to major
histocompatibility complex (MHC) proteins on the surface of other cells,
this stage called activation of the helper T cell which in turn promote the
activation of other classes of lymphocyte such as B cells or cytotoxic T
cells, these activation depended on many signals such as :-
1. Signal of the Macrophage activation :
1. A tissue macrophage lives for approximately 2 – 4 months. During
this time, some macrophages remain immobile while other wander
by amoeboid motion, in either case the cell continually samples its
surrounding environment by pinocytosis (occurs through formation
of minute surfaces ), receptor – mediated endocytosis (occur by the
binding of soluble ligand to one or more specific surface receptor). &
zippering process (occur through an extensive array of receptor on
bacterial surface).Whenever it encounters certain stimuli, the
macrophage undergoes a process known as activation, in which it
rapidly increases its metabolic rate, motility & phagocytic activity.
2. Signal of activation T.H. cells :
The activation of H.T cell occurs early in an IR & requires 2 signals :-
a. The first signal is provided by binding of the T cell receptor to the Ag
peptide MHC II complex on the APC surface.
b. The second signal is provided by activate APC, which expressed on
their surface specific ligand known as Costimulators, such as proteins
in the B7 family that are necessary to activated at H cell after contact
with accessory molecule CD28 on the surface of T cell.
In addition the APC also release IL – 1 which acts on APC itself in an
autocrine manner by increasing surface expression of class II MHC
proteins & of various adhesion molecules & therefore strengthens
binding of the TH cell & enhances Ag presentation & acts on TH cell in
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a paracrin manner to promote IL – 2 secretion & IL – 2 receptor
expression.
c. These 2 signals induce the helper T cell to begin secreting interlukin
(IL – 2) & also to begin expression specific high – affinity IL – 2
receptors on its surface.
3. Signal of activation cytotoxic T – cell :
a. The first signals provided by binding of the T cell with specific Ag in
the context of a class I MHC molecule on the surface of a target cell,
this signal will induces high affinity IL – 2 receptor on the T cell.
b. The second signal is provided by Activated T helper cell which
secretes IL – 2 that activate T cell. The cytotoxic T cell activation by
receiving these signals acquired cytotoxic activity, enabling it to kill
the cell to which it is bound by releasing specific toxins onto the
target cell or by inducing the target cell to commit suicide (
Apoptosis: an evolutionary conserved form of cell suicide, allows
multicellular organisms to eliminate damaged or excess cells in
order to maintain tissue homeostasis. Dysregulation of apoptosis is
associated with various pathological conditions, including cancer
and neurodegenerative disorders ).The different between apoptotic
and necrotic cell death process show in this figure in which
Apoptosis includes cellular shrinking, chromatin condensation and
margination at the nuclear periphery with the eventual formation of
membrane-bound apoptotic bodies that contain organelles, cytosol
and nuclear fragments and are phagocytosed without triggering
inflammatory processes but necrotic cell swells, becomes leaky and
finally is disrupted and releases its contents into the surrounding
tissue resulting in inflammation.
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4. Signal of Activation B lymphocyte :
a. The B cell unlike T cell, B cells recognize Ag in its free non processed
form. There for some highly polymeric Ag that cross – link multiply Ag
receptor are sufficient to activation of B – cell.
b. Most monomeric Ag are not sufficient to activate B cell because the
binding Ag alone with Ig receptor on B cell generate only an
incomplete signal which fall to activate B cell; such as induction IL – 2
receptor which make the cell more receptive to other stimuli
provided by activated TH cell which either secreted soluble cytokine
called Helper factor.
Such as CD40 on B cell surface which bind with CD40L found on TH cell
only after they become activated.
The direct contact can aid activation of B cell that has not bound Ag,
this is called bystander activation.
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c. Certain accessory molecules on the B cell such as CD22 complement
receptor & class II MHC protein can send signal that promote B cell
activation.
d. The B – cell in the same instance must act as APC in order to be
activated, because it does not only receive signal from the Ag bound
to it but also become ready to direct contact with helper T cell.

The major histocompatibility complex
(MHC):The immune system is encoded by set of gene families namely:
a) Immunoglobulin gene families (Informatcatiol gene families)
b) Major Histocomputiblity gene families.
The major histocompatibility complex (MHC) is a large genomic region
or gene family found in most vertebrates. It is the most gene-dense
region of the mammalian genome and plays an important role in the
immune system and autoimmunity. The diversity of MHC is important in
the immune diversity in the population. The proteins encoded by the
MHC are expressed on the surface of cells in all jawed vertebrates, and
display both self antigens (peptide fragments from the cell itself) and
nonself antigens (e.g., fragments of invading microorganisms) to a type
of white blood cell called a T cell that has the capacity to kill or coordinate the killing of pathogens and infected or malfunctioning cells.
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