1. Classification
Genes that regulate & code for the MHC of human are located on the sixth chromosome,
clustered in amultigene complex for three subgroups called class I, class II, class III as show
in this table:
Name
Function
Expression
MHC
class I
All nucleated cells. They present antigen
molecules & code for Antigen-processing
fragments to cytotoxic T-cells via the CD8
markers that regulate acceptance or
molecule and also bind inhibitory
rejection of tissue graft.
receptors on NK cells.
MHC
class II
On most immune system cells, specifically
on antigen-presenting cells. they present
Modulate antigen loading onto MHC class
antigen fragments to T-helper cells by
II proteins in the lysosomal compartment.
binding to the CD4 receptor on the Thelper cells.
MHC Encodes for other immune components,
such as complement components (e.g.,
class III
C2, C4, factor B) and some that encode
region
cytokines (e.g., TNF-α)
Variable
2. Responses
The MHC proteins act as "signposts" that display fragmented pieces of an antigen on the
host cell's surface. These antigens may be self or nonself. If they are nonself, there are two
ways by which the foreign protein can be processed and recognized as being "nonself".
 Phagocytic cells such as macrophages, neutrophils, and monocytes degrade foreign
particles that are engulfed during a process known as phagocytosis. Degraded particles
are then presented on MHC Class II molecules.
 On the other hand, if a host cell was infected by a bacterium or virus, or was cancerous, it
may have displayed the antigens on its surface with a Class I MHC molecule. In
particular, cancerous cells and cells infected by a virus have a tendency to display
unusual, nonself antigens on their surface. These nonself antigens, regardless of which
type of MHC molecule they are displayed on, will initiate the specific immunity of the
host's body.
3. Uses of HLA typing
a- Determination of HLA compatibility prior to transplantation.
b- Paternity testing.
c- Establishing HLA disease associated,
4. Disease associated with HLA antigen have several characteristic
a- Of unknown cause& unknown pathophysiology mechanism, with hereditary pattern
of distribution but weak penetrance.
b- Associated with immunologic abnormalities.
c- Have little or no effect on reproduction.
Example:For MHC associated disease:
 Dermititis herpitiformis
 Insulin-dependent diabetus mellitus
 Autoimmune chronic active hepatitis.
 MHC & Disease :1. Certain human diseases occur more frequently among individual who carry particular
MHC alleles. These diseases include the susceptibility to certain in factions agents. As
well as to a number of auto immune disorders.
For exam ankylosing spondylitis whose cause is unknown but another of Caucasian
parent with this disease express HLA Balled designated.
2. HLA associated susceptibility to infection disease HLA could be due to an inability of the
particular HLA protein to associate effectively with processed Ag. From the pathogen
there by limiting the capacity of the individual to mount an immune response against it.
3. Animal populations that reduced MHC polymorphism may predispose a population to
infections disease. This accrue because the reduced polymorphism limits the range of Ag
to which a population can respond.
4. Although there may be individuals within a species that are unable to respond to a given
pathogen because they lack the appropriate MHC alleles. Polymorphism ensures that at
least some individuals will be able to respond & that the species as a whole will survives.
Antigen, Immunogen :
Immunogen : is any agent that is able of inducing an immune response such as M.O or
tissue graft; or acquired immune response arise as a result of exposure to foreign stimuli,
the compound that evokes the response is referred to either as antigen or immunogen.
Antigens : are compounds that are incapable of inducing an immune response& they are
capable of binding with the component of the immune system that has been induced
specifically against them. Thus all immunogens are antigens but not all antigens need to be
immunogens.

Required for immunogenecity :Substances must posses the following characteristics to be immunogenic:
A) Foreignness :
Animals normally don’t respond immunologically to itself, thus for example if a rabbit
was injected with its own serum albumin will not mount an immune response. It
recognizes the albumin as itself, by contrast if the rabbit serum albumin is injected into
guinea pig. The guinea pig recognizes the rabbit serum albumin as foreign & mounts an
immune response against it.
B) Method of administration :
Quantitatively of substances that have no effect when injected intravenously may evoke
great Ab response when injected subcutaneously.
C) Genetic constitution of the host animal :
For example pure poly saccharides are immunogene when injected in to mice or human
but not when injected into guinea pigs or rabbits.
D) Chemical composition:
- large macromolecular proteins are most potent immunogen
- polysaccharide & short polypeptides & some synthetic organic polymers are also
immunogen but the pure lipids & nucleic acid have not been show to be immunogenic,
although Ab that reach with them can be elicited by immunization with nucleoprotein or
lipoprotein complex. Therefore this material called Hapten which are substances and
called HAPTENS if they fail to stimulate immune-response in their native form due to
their low M.WT & their chemical simplicity. These compounds are not immunogenic
unless they are conjugated to high M.WT Physiochemically complex carriers. Thus an
immune response can evoke thousand of chemical compounds.
The hapten simply serves as one of the residues that contribute to the epitope together
with amino-acid residues from the carrier.
This method has practical importance since it provide simple way of obtaining antibodies
directed against any small molecule regardless of its inherent immunogenicity. Therefore
the hapten can act as antigen.
E) High molecular weight :
Immunogenic is that it must have a certain minimal molecular weight. In general,
compounds that have M.WT less than 1000 Daltons for example penicillin &
progesterone are not immunogenic. Those of M.W between 1000 – 6000 like insulin may
or may not be immunogenic & those of M.WT greater than 6000 Daltons, for example
albumin tetanus toxins are generally immunogenic.
F) Chemical complexity :
It’s a certain degree of physiochemical complexity such a polymer of lysine which is of
M.W 3000D are seldom good immunogenic, similarly a photopolymer of poly –  - D –
glutamic acid (the capsular material of Bacillus antharacis of M.W 5000D is not
immunogenic); the absence of immunogenecity is because of these compounds,
although they are of high M.W are not sufficiently chemically complex. In general, an
increase in the chemical complexity of compounds results in increase of the
immunogenecity.
G) Degradability:
The substance must be susceptible to partial enzymatic degradation that takes place
during antigen processing by presenting cells such as macrophages. Substances which are
resistant to enzymatic degradation are not immunogenic.

Antigenic determinant (epitop) :-
These structures are referred to as antigenic determinant or epitopes & represent exposed
active area of the molecule with which an antibody can combine & can be found by
immunoglobulin proteins, therefore called B-cell epitopes but T-cell epitopes are recognized
by T – lymphocytes only often being processed & presented in association with a MHC
protein on the surface on an (APC).
There are many characteristic for epitopes which are :
1. Conformational & linear epitop:
Conformational epitop
linear
2. Immunodominance: large Ag usually contains numerous epitopes, for example one
epitope may evoke Ab quantities & with high binding affinity; than do other available
epitop such appeared epitope is said to be immunodominant.

Cross – reaction :
Identical epitope may be found on a number of different antigenic molecules.
As a result Antibodies directed against one antigen may be found to react unexpectedly
with antigen from apparently unrelated source.

Major classes of antigens :
Most materials that serve as antigens fall into the following chemical categories:
1.
2.
3.
4.

Proteins & poly peptides
(enzymes, albumin, antibodies, hormones, exotoxins).
Glycoproteins
(blood cell markers).
Nucleoproteins
(DNA complexed to proteins but pure DNA is not).
Polysaccharides
(certain bacterial capsule & lipopolysaccharide).
Definition of antigenic specification :
In general Antigens may be classified into two major types:
1. Exogenous Ags : are those that are presented to the host from the exterior in the
form of micro – organisms, pollen, drugs or pollutant.
2. Endogenous antigens : are those that are found within the individual & include many
types of antigens, allogenic antigens (Homologous).

Some terms used by immunologist for detection of Ag types:
1. Autologous Antigen  is ones own Ag, which under appropriate circumstance
includes auto antibody formation, autologous Ag is thus synonymous with auto-self
antigen.
2. Heterologous Antigen  is merely an antigen different from that used in an
immunization, it may or may not reach with the antiserum, depending on its chemical
similarity to homologous antigen.
3. Homologous Antigen  is simply that antigen used in the production of antiserum.
In serology (serologic tests) a heterologous antigen may be used as a negative control
for any non specific reaction arising from errors in performing the serologic test or in
the preparation of the serologic reactants.
4. Cross reactive Antigen  heterophil (Heterogenic) antigens are antigens that exist in
unrelated plants or animals but are either identical or so closely related that
antibodies to one will cross – react with the other. In many instances, heterophil
antigens are polysaccharides.
 Antigen Nomenclature
(T – Cell dependant & independent antigens) : T. dependant Ag :
The antigens that require T – cells in order to generate an immune response T. dependant
Ag & have this characteristic :
1. T – cells are required for the high level of immunity that follows booster injections of
antigen.
2. Only (TD) antigens are able to initiate the booster or memory response.
3. The clonal expansion of Ag specific helper T cell is required for many of the characteristic
features of secondary Ab response & that an immunogen must contain at least on T-cell
epitope in order to induce functional immunological memory.
 T – cell – independent (TI) antigen :Antigens that stimulate B-cells without the intervention of T-cells & characteristic :
1. To stimulate an optimal immune response to (TI) antigen, the antigen dose must be
selected carefully. Too little antigen will be inadequate & too much will favor the
development of immunological tolerance rather than immunity.
2. (TI) antigens are structurally simpler than (TD) antigen (it’s not proteins). Diphtheria
toxoid, bovine serum albumin, hemocyaneis…are usually (TD) antigen.
3. (TI) antigens are often composed of a limited number of structural units that are
repeated through the molecule. This arrangement limits the variety & complexity of their
epitope.
4. Though (TI) antigens are less complex than (TD) antigen, they are often catabolized more
slowly in vivo.
5. One striking property of the responses to thymus independent Ags, is that no apparent
memory even after repeated exposure & the Ab responses are occur after a relatively
long lag period & in all other respects resembles primary humeral response.
Comparison of T- cell independent & dependent Ags
(TI) ANTIGEN
(TD) ANTIGEN
1. required T cells
No
Yes
2. initiated memory
response
No
Yes
High
Low
Simple, repetitive
More complex
IgM & IgG3
IgM, IgG, IgG2, IgG3, IgG4, IgA, IgE
Limited
Varied
Slow
Fast
3. dose dependency of
immune response
4. structure
5. class of antibody
formed
6. idiotype of Ab formed
7. metabolism in vivo
8. induction of tolerance
9. Ag processing
Easy
More difficult
May not be
required for all
Required
 Antibody & Immunoglobulin
The Ab are bifunctional molecules which bind specifically to Ags & also initiate a variety of
secondary phenomena such as complement activation or opsonization
 The 4 – chain Basic unit :
1. Each Ig molecule is made up of 2 different types of polypeptides, the larger of these
called heavy (H) chains, but smaller light (L) chains & the Ig molecule contain equal
number of heavy & light chain.
These chains are held together by non covalent forces & also by covalent interchange
disulfide bridges & both the heavy & light polypeptide chains are composed of a number
of folded globular domains. Light chains always contain 2 of these domains, whereas
heavy chains contain either 4 or 5.
2. The light & heavy chains in any single Ig protein are identical but the sequences of these
chains vary widely, in both heavy & light chains; this variability is confined largely to the
N – terminal domain whereas the sequence of the other domains remains relatively
constant. For this reason N – terminal domain in a heavy or light chain is called variable
region but the other domains are called constant region.
3. All light chains can be classified into 2 types called (kappa ) & (lambda  )
4. There are 5 (γ – α – μ – δ – ε) different classes of Ig heavy chain which differ in their CH
– region sequences & in their physical & biological properties. The γ and α classes are
divided into subclasses ( γ1, γ2, γ3, γ4 and α1, α2 ).
5. The Ig are generally natural present in the blood human without previous Ag stimulation
but Ab are produced by B cell after antigenic stimulation.
 Major functional regions of the immunoglobulin in
molecule
1. Fab fragment
is monovalent with respect to Ag – binding site which contain antigen
binding site.
2. Fc region
most of the secondary biological property such as (complex activation) is
determine by sequence in Fc region & Fc binding site for IgGs that attach via Fc region to
the various cell types (Macrophages, neutrophils, mast cells).
3. Hinge region
has loose secondary structure that confers flexibility, enabling the 2
arms to move relatively freely with respect to each other (located between the CH1 &
CH2 domain).
Properties of Ig class :
 IgG properties
1. The major immunoglobulin & the most abundant Ab produce during secondary H.I.R in
the blood.
2. It consists of a monomer.
3. Passes through the placenta.
4. Diffuses readily in to extra vascular spaces.
5. Enhances phagocytosis of microorganism.
6. Activate complement after its reaction with antigen.
7. After attachment to microorganism attracts killer cells..
8. Macrophages & other cell type express surface receptor that bind the Fc region of IgG
molecule.
 IgM properties
1.
2.
3.
4.
5.
6.
7.
8.
9.
The first Ig to appear after immunization & predominant in early P.I.R to most Ag.
It is a pentamer (5 units).
Does not pass through placenta.
Active in phagocytosis (500 – 1000  more than IgG).
Activate complement (1000  more activate than IgG).
Agglutination particulate Ags (20  than IgG).
It has 10 active sites, only 5 are active but all react as hapten.
It found as natural Ab against such Ag as the blood group determinant.
IgM (usually accompanied by IgD) is the most common Ig express of the B cell.
 IgA properties
1.
2.
3.
4.
5.
6.
7.
The major Ig in extra cellular excretions like milk, tear, mucous, urine, bile.
Monomer in serum, dimmer in excretion.
Does not pass through placenta
Weak in phagocytosis.
Activate alternative pathway of complement.
Weakly active in agglutination.
Protects outside surfaces of body.
 IgD properties
1. Found mainly on B – lymphocyte & although it found on surface of these cell it is
rarely secreted in significant amount.
2. Monomer.
3. It is relatively liable to destroying by heat.
4. Its biological activity is not known.
 IgE properties
1.
2.
3.
4.
5.
6.
7.
8.
Mainly on mast cells, attached to it by Fc..
Monomer.
Does not pass through placenta.
Not active in phagocytosis.
Does not activate complement.
Attaches to mast cells & Basophiles.
Responsible for defense of body against parasite infection & helminthes.
Active in hypersensitivity. When these Ab attach to the surface of mast cell act as Ag
receptor, therefore when contact with Ag the mast cell releases inflammatory
mediator substance that produce many acute manifestation of allergic disease.
 Kinetic of the antibody response following immunization :
 Primary response:
The first exposure of an individual to a particular immunogen is referred to as the primary
immunization & the measurable response that ensures is called the primary antibody
response may be divided into several phases, as follow :
1) Latent or lag phase: after initial injection of antigen, a significant amount of time elapses
before antibody is detectable in the serum. The latent period includes the time taken for
T & B cells to make contact with the antigen to proliferate & to differentiate.
2) Exponential production phase: during this phase the concentration of Ab in the serum
increase exponentially.
3) Study state: during this period production & degradation of Ab are balanced.
4) Declining phase: finally the immune response begins to shut down & the concentration
of Ab in serum decline rapidly.
 Secondary response:
A second exposure to the same immunogen results in a secondary response. This second
exposure may occur after the response to the first immune event has leveled off or has
totally subsided (within weeks or even years).
The secondary response differs from the primary response in many aspects :
1) The lag phase is considerably shorter.
2) Ab may appear in less than half the time required for the primary response.
3) The production of Ab is much greater & higher concentration of Ab is detectable in the
serum.
4) The production of Ab may also continue for a longer period, with persistent levels
remaining in several months or even years later.
5) There is a marked change in the type & quality of antibody produced in the secondary
response. .
6) The capacity to make a secondary or memory response may persist for a long time (years
in human) .
CHARACL
PRIMARY I. S.
SECONDARY I. S.
Mainly by non B. cell
B lymphocytes
increasingly important
Relatively high
Low
5-10 days
Relatively 2-5 days
Relatively low
Relatively high
Mostly IgM
Other class IgG, IgA
Relatively low
Relatively high
7. Mono specific Ab
Abundant
Rare
8. The periods of reaming of
Low period
High
1. Ag presentation
2. Ag concentration needed
or induce response
3. Ab response lag phase
4. Peak concentration
(Ab levels)
5. Classes
6. Ag affinity
Ab
in
the
stem
at
detectible levels
 Plasma cells & memory cell:
Plasma cells are proteins factory, producing about 2000Abs/sec, in their short life time 5 – 7
days. Memory cells are capable of initiating the antibody mediated immune response upon
detecting the particular antigen molecule for which they are genetically programmed. They
live longer than plasma cells.
Memory cells may live for several years or decades & are responsible for the human system
rapid secondary Ab response to the same Ag.
 The Ag – Ab reaction:
(A) This reaction has the following feature :
a. It’s highly specific.
b. The binding of Ag to Ab does not involve covalent bond, but only relatively weak
forces (H – bonding, vanderwals forces).
c. The entire molecule reacts but not fragments.
d. The combination is firm & reversible.
e. There should be an optimal proportion between size & number of Ag with that of Ab.
(B) The globulins protein in serum:
a.
Globulin
γ
β
α1 α2
b.
Globulin
γ
β
α1
α2
a. Tracing of an electrophoretic separation of normal serum.
b. Some type of tracing of serum from a patient with multiple myloma.
Albumine
(C) Nature of antigen-antibody reactions :
1-Lock and Key Concept : The combining site of an antibody is located in the Fab portion of
the molecule and is constructed from the hyper variable regions of the heavy and light
chains. X-Ray crystallography studies of antigens and antibodies interacting shows that the
antigenic determinant nestles in a cleft formed by the combining site of the antibody.
thus, our concept of Ag-Ab reactions is one of a key (i.e. the Ag ) which fits into a lock (i.e.
the Ab ).
2-Non-covalent Bonds : The bonds that hold the Ag in the antibody combining site are all
non-covalent in nature. These include hydrogen bonds, electrostatic bonds, Van der waals
forces and hydrophobic. Multiple bonding between the Ag and the Ab ensures that the Ag
will be bound tightly to the Ab.
3-Reversible : Since Ag-Ab reactions occur via non – covalent bond , they are by their
nature reversible .
(D) Affinity and avidity :
1) Affinity : Antibody affinity is the strength of the reaction between a single antigenic
determinant and a single combining site on the antibody . It is the sum of the attractive
and repulsive forces operating between the antigenic determinant and the combining
site of the antibody.
Affinity is the equilibrium constant that describes the Ag-Ab reaction, most antibody
have a high affinity for their antigens.
2) Avidity : Avidity is a measure of the overall strength of binding of an antigen with many
antigenic determinants and multivalent antibodies. Affinity refers to the strength of
binding between a single antigenic determinant and an individual antibody combining
site whereas avidity refers to the overall strength of binding between multivalent
antigens and antibodies. Avidity is influenced by both the valence of the antibody and
the valence of the antigen. Avidity is more than the sum of the individual affinities.
(E) Monoclonal Antibody production :
 Clinical immunology :First\\ Immunodeficiency :
There are 2 types :
(A) Primary imm.def. states :
These occur in the human as result of any stage of differentiation in the whole immuno
system.
 Defect in phagocytic cells, complement pathway or B-cell system lead to infection with
bacteria which eliminated by opsonization & phagocytosis.
 T- cell deficiencies are susceptible to viruses & molds which are normally eradicated by
(CMT).
(B) Secondary immunodeficiency:
These may arise as a secondary consequence of malnutrition & lymphoproliferation disorder
& some agents such as cytotoxic drugs & viral infection, AIDS.
Second\\ Hypersensitivity :
Allergy (hypersensitivity) allergy is an altered state of reactively to an antigen or hapten,
hypersensitivity means a heightened reactively.
The 2 terms are interchangeable on the basis of common usage & the pathological reaction
can subsequently elicited by that antigen or by structurally similar substance.
 Immunological basis of hypersensitivity:
1. Immunization & the formation of antibodies does not uniformly leads to state of
2.
3.
4.
5.
resistance or immunity e.g immunization with bovine γ globulin, sheep RBC …..Etc.
Allergic or hypersens. Responses are immunologic in origin.
The initial stage in their development is an exposure to an antigen (called sensitizing
exposure).
Sensitization is expressed after immunologic waiting period of 5-10 days.
The sensitivity can be demonstrated by injection a second dose of antigen.
 Classification of
hypersensitivity:
According to time required for host sensitized.
1. Immediate hypersensitivity. This response appear within a few second or a few
minutes after administration of second dose of antigen. This reaction disappear
rapidly. It depends on IgE.
2. T- lymphocyte – mediated hypersensitivity delayed hypersensitivity (DH).
The response in this type is slow in developing reach its maximum after 24-72 hr after
exposure to antigen.
Comparison of IgE &T. cell mediated hypersensitive
T -cell mediated
IgE- mediated
Second response.
Appear with in few minuts
fades with in few hrs
(immediate).
Develop & rades
gradually 24- 72 hrs
(delayed).
2. Special target tissue.
Usually smooth muscle but
organ vary with spec.
Generalized tissue
involvement
May occur.
Occurs.
Yeas: IgE.
None.
Vascular.
Vascular & relatively a
Vascular.
6. Histology of skin reaction.
Neutrophils , eosinophils
edema , wheal & erythema.
Mononuclear some
Neutrophils less edema
& wheal erythema .
7. Mediators.
Histamine, serotonin, kinins.
lymphokines .
Yes, relatively easy.
Yeas, with difficult .
1. Timing of response after.
3. Tissue death.
4. Humoral factors
involvement.
5. Type of tissue involved.
8. Immunotherapy.
Immunophathologic classification of hypersensitivity according to this system
four type of hypersensitivity are included :-
1. Anaphylactic type of reaction is that in which immunoglobulin of the IgE type
synthesized by plasma cell become attached to mast cells & basophiles through the in Fc
portion.
Fab regions protrude from the cell surface & when combined with antigen alter the
permeability of these cells pharmacologically active substance such as histamine &
serotonine released by the cells affect the smooth muscles primary plasma cell.
2. Cytotoxic allergy: this involves the death of cells bearing Ab attached to antigen , Abs are
of IgG & possibly IgM classes react directly with antigen on the surface of tissue cells.
Complement participate in this reaction & promot cytolysis or cytotoxic reaction
E.g. hemolytic reaction drug, allergies, autoimmune disease & allograff rejection.
3. Immune complex reaction antigen antibody complex form in the soluble or fluid phase
of tissue or in blood & then deposit on vessel walls & glomerular membrane to interrupt
normal physiological process. This lead to complement become activated & release
chemotactic factors. The attracted leucocytes release enzymes possibly other agent that
injure local times, E.g. Arthur reaction auto immune reaction, glomerlonephritis.
4. Delayed type reaction :- the cell mediated hypersensitivity reaction involved antigen
sensitize T-cells which respond directly or by the release of lymphokines.
E.g. dermatitis & allergies of infections. The delayed appear of an indurate &
erythematus reaction which reaches a maximum at 24-48 hrs & is characterize histology
by with mononuclear phagocytes & lymphocytes.
Type of hypersensitivity reaction
 Immunoglobuline
 Ag involved
 complement
Anaphylactic
Cytotoxic
I gE
IgG ,
possibly
other
IgG , IgM …
Autologous
Auto. or
Heterologous
Heterologous
Heterologous
Immunocomplex
T-cell dep.
Non
Auto. Or
No
Yes
Yes
No
Mast cell &
basophiles.
Red, white
blood cell ,
platelets
Host tissue cells
Host tissue
cells
Mast cell
product &
other
Complement
dependent
cytolysis
Complement
dependent
reaction
Lymphpkines
Anaphylaxis ,
hay fever ,
food allergy
Transfusion
reaction , Rh
disease
Arthus reaction
serum sickness
Allergy of
infection ,
contact
dermatitis
involved
 cellular
involvement
 chemical
mechanism
 Examples
Third\\ Tumor immunology :
1. Changes on the surface of tumor cells
Some tumors express genes which are silent in normal tissue:-
-
Tumors express weak Ag associated with in oncogenes.
Many tumors express normal differentiate Ag specific for that tissue.
Tumors may lack class I MHC molecules.
Dysregulation of tumor cells frequently causes struct. Abnormalities in surface
carbohydrate str.
2. Immune response to tumors 2
 Cytotoxic T–cells may provide surveillance & cause tumor cell destruction or apoptosis.
 NK cell probably play a role in containing tumor growth & melaslases. They can attack
MHC class I negative tumor cell because the class I MHC imparts inactivation signal to
NK cell.
Fourth\\ Autoimmune disease :
This disease associated with certain disease which forms a spectrum. At one pole the
autoantibodies & the lesion are organ specific with the organ acting as the target for
autoimmune attack (e.g. hashimotos thyroiditis). At other pole the autoantibody have wide
activity& the lesion relating to deposition of circulating immune complex there for this
called non organspecific or systemic autoimmune disease e.g. (SLE).

Genetic & environmental influences :-
 Multif genetic factors increase predisposition to autoimmune disease these include HLA
tissue type.
 Females have higher incidence of autoimmunity than males, perhaps due to hormonal
influences.
 Environmental influences in many disorders: both microbial & non microbial factors.
 Microbes may initiated auto immune disease by a number of mechanisms, including
molecular or by acting as adjuvant or super antigen.
 Autoimmunity can arise by pass of T- helper tolerance to autoantigens
through
abnormal modification of the autoantigen by break down & combination with
or
cross reaction with exogenous antigen can provide new carriers determination which
can activate T-cell.
 B-cell & T-cell can be stimulated directly by superantigen which are a class of bacterial
toxin that have the ability to bind both class II molecular & the TCR ß chain outside of
the peptide binding groove.
 Autoimmunity can arise through by pass of regulatory mechanism.
 The derepression of class II genes could give rise to inappropriate cellular expression of
class II so breaking the silence cellular autoantigen & autoreactive T inducer.
 TH1 & TH2 imbalance may result in overproduction of inflammatory cytokines.
Fifth\\ Immunological tolerance :
1. Definition
The failure or relative reduction in immune response on reexposure or exposure to
certain specific antigen.
2. Tolerance types
tolerance may be peripheral which included by soluble antigen , soluble immune
complexes , blocking antibodies or it may be central which is attributed to absence of
lymphocyte production , absence of Ag receptors & or due to non-production of
lymphocyte receptors. Tolerance may be complete or incomplete.
3. Toleragens
Antigen which induce tolerance to termed as toleragens.
toleragens are of tow types low dose toleragens & height dose toleragens . Soluble Ags
are more toleragens than articulate. Ags tolerance occurred in T-cell rapider than in B –
cells.
4. Characteristic
 The I. S. remains specifically to tolerant toward the many self determinant to which it
is continually exposed.
 The tolerance accrue by either B cell (that could be achieved either by eleminating any
cell that express an autoreactive Ab or by permining such cell to survive in
a
functionally & inactive state) or T cell which become tolerance by remove in
compination with self MHC.