1. Antigen:
Antigen is a substance usually protein in nature and
sometimes polysachharide , and glycoproteins which when
introduced into vertebrate host can induce the specific
immune response either by producing specific antibodies or
especially sensitized T-cells or both.
Types of antigen:
1. Complete antigen or immunogen: Immunogenecity is the
inherent ability of a substance to induce the specific
immune response resulting in the formation of
antibodies.Immunogen are foreign substance which can
induce an immune response by themselves. Immunogen
are generally high molecular weight substances and
proteinous in nature.
2.
3. 2. Incomplete antigen or hapten: Hapten or incomplete
antigens are those which can't induce an immune
response by themselves. Haptens are not immunogenic
but are antigenic because they can react with immune
lymphocytes or antibodies.Haptens being incabable of
inducing immune response by themselves so they are
converted into immunogen with the specific molecule
known as carrier.Haptens are usually low molecular
weight substances and non-proteinous in nature.
Hapten-carrier conjugates have
native antigenic determinants of
the carrier as well as new
determinants of the hapten
4. All molecules that have the property of immunogenicity
also have the property of antigenicity but the reverse is not
true. For e.g some small molecules like haptens are
antigenic in nature but incapable by themselves of
inducing immune response.
Carrier molecule: The carrier molecules for hapten may be
serum proteins such as albumin,globulin or synthesized
polypeptides.Haptens are of two types:
•Complex haptens are relatively large molecules and
combine with specific antibody forming visible
precipitate.e.g Capsular polysacharides of Streptococcus
pneumoniae,Cardiolipin etc.
•Simple haptens do not form visible precipitate.
5. Factors influencing Immunogenicity:
The immune system actually recognize particular
macromolecules generally either proteins or polysaccharides.
Proteins are the most potent immunogens than
polysachharides.
Immunogenicity is infleunced by following 6 properties of
immunogen.They are:
•Chemical Composition:Majority of immunogens are protein
and glycoprotein in nature.They are the strongest antigens
because they have the largest array of potential building
blocks(amino acids).Heteropolymers(composed of different
amino acids)are usually more immunogenic than
homopolymers(composed of single amino acids).
6. •Molecular Size: Molecular size plays an important role in
immunogenicity of the molecule.Usually the larger
molecule is better immunogenic.Molecules having less
than 10,000 D mass cant induce immune response and are
called poor immunogens.e.g Drugs are poor immunogens.
•Genetic constituent of Host:The genetic constitution of an
immunized animal also influences the type of immune
response as well as the degree of response.For e.g
If polysachharide is injected, than no immune response is
induced by rabbit.
If polysachharide is injected than immune response is
induced by Guinea pig
7. •Foreignness:The immune system possess the
capacity to distinguish between self and non self
molecules. Antigen are non-self in nature because
our immune system generally produces no immune
response against self antigen. The greater the
phylogenetic distance between two species, the
greater the structural difference between them.For
.e.g The antigen Bovine serum albumin is not
immunogenic when injected into cow but strongly
immunogenic when injected into rabbit.
8. •Method/Route of administration and Dose:Dose
and route of administration of antigen is also a
factor of immunogenicity.Antigen administrated
intravenously is carried first to spleen where as
antigen administrated subcutaneously movest first
to local lymph nodes.Differences in the lymphoid
cells may be reflected in subsquent immune
response.An insufficient dose will not stimulate an
immune response and excessive dose also cant
induce immune response but are tolerable.For e.g
An 0.5 mg dose of antigen fails to induce an
immune response in mice,whereas a thousand fold
lower dose of same antigen can induce immune
response in Guinea pig.
9. •Antigen processing and presentation:The
development of both humoral and cell mediated
immune response requires interaction of T-cells with
antigen that has been processed and presented
together with MHC molecules. Larger, insoluble
macromolecules generally are more immunogenic
than small and soluble ones. Macromolecules or
Antigens that cannot be degraded and presented
with MHC molecules are poor
immunogen.Molecules which are polymer of L-
amino acids can easily degraded due to the presence
of degradative enzymes than D-amino acids.So our
body can recognize L-amino acids and acts as high
immunogens.
10. Antigen determinants(epitopes)
Immune cells donot interact with or recognise an entire
immunogen molecule,instead lymphocytes recognize
discrete sites on the macromolecules called epitopes or
antigenic determinants.
Epitopes are the sites on
or within the antigen with
Which antibodies react.
Immunogens or
macromolecules may
contain 1 or more epitope
but all epitope are not immunogenic.Epitopes are very
small i.e just four or five amino acids or monosachharides
residue 3 D structure and steric structure.
11. Epitopes determine the specificity of the antigen
molecule and induce the antibody response.
Antibodies are specific for epitopes.
There are two types of epitopes. They are:
1.B cell epitope
2.T cell epitope
B cell epitope: Antigenic determinants recognized
and bound by the B-cell receptor is the B cell
epitope.. Epitopes recognized by the B-cell
receptor are located on the surface of the antigen.
B cells recognize soluble antigen that is free in
solution,so B cell epitope should match paratope
of Antibody.
12.
13. T cell epitope:T cell receptors never bind free
antigens or epitopes. It can bind epitope that are
bound to MHC molecule. Epitopes recognized by the
T-cell receptor are often located in the inner,
unexposed side of the antigen, and become
accessible to the T-cell receptors after proteolytic
processing of the antigen.
T cell epitopes must be processed inside the cell so
as to bind to the MHC molecules. Hence T cell
bound to that epitope which are presented by antigen
presenting cells(APCs).
14.
15. Origin of Antigen:
Antigens can be classified in order of their origins.
•Exogenous antigen: Exogenous antigens are those which are
entered into the body from outside e.g by inhalation,ingestion or
injection. By endocytosis or phagocytosis, exogenous antigens are
taken into the antigen-presenting cells (APCs) and processed into
fragments. APCs then present the fragments to T helper cells (CD4+)
by the use of class II MHC molecules on their surface.
•Endogenous antigen: Endogenous antigens are generated within
our cells as a result of normal cell metabolism or because of viral or
intracellular bacterial infection. The fragments are then presented on
the cell surface in the complex with MHC class I molecules. If
activated cytotoxic CD8+ T cells recognize them, the T cells begin to
secrete various toxins that cause the lysis or apoptosisof the infected
cell.
16. •Auto antigen: An autoantigen is antigen which is protein
and are recognized as non self antigen by the immune
system of patients suffering from specific auto immune
diseases.The diseases condition where the immune system
attacks its own body parts is called auto immune system.
17. Sources of antigen:
•Particulate:
Cells e.g tumor cells, RBC, Leukocytes
Microorganisms e.g bacteria,viruses.
•Soluble antigens
Proteins
Polysachharides
Nucleic acids
Exotoxins and Super antigens.
18. Types of Antigen:
1. T-dependent antigens:T dependent antigens are those
which produces antibodies with the help of T-cells. In T-
dependent antigen T-cells produces cytokines which
gives the message to the B-cell for the production of
antibody.The produced antibody is monoclonal in
nature.
2. T- independent antigen:T-independent antigens are those
which can directly stimulate the B-cells to produce
antibody without the requirement of T-cell help.e.g
Lipopolysachharides.Due to polymeric structure of
LPS,B cell don’t require help of T-cell for the
production of Antibody. The produced antibody is
polyclonal in nature.
19.
20. 3. Super antigen: Super antigens activate a large number of
T-cells which harms the body.In some cases exposure to
super antigens can be fatal.e.g Styphylococcal toxic
shock toxin,Streptococcal pyrogenic exotoxin
etc.Normally when ag is encountered in body only 0.5%
T cells are activated but when super antigens are
encountered 25% T cells are activated.
Symptoms when super antigen is encountered are:
• High T cell activation
• Production of massive cytokines.
• Systemic effect like vasculation leakage
• Hypotension,fever,chill and shock and death.
Superantigens bind non specifically to the ß sub unit of
T-cell receptor and at the lateral site of MHC II
molecule.
21. 4. Cross-reactivity antigen (Heterophile antigen):
Certain antigens of similar nature present in
different tissues of more than one species are called
heterophile antigens or Substances that stimulate the
production of antibodies capable of reacting with
tissue of a wide variety of un related animals or
plants are called cross reacting antigen.
• Forssman antigen:
• Rickettsial antigen(Weil-felix reaction)
• Epstein Barr virus:
• Cardiolipin antigen:
22. • T cells recognize linear peptides not whole proteins.
• T cells only recognize epitopes when they are complexed
to MHC molecules.
• Therefore protein antigens must be processed and
presented by other cells to be recognized by T cells.
• This process is referred to as antigen processing and
presentation.
– Note: the association of antigenic peptides /MHC is a
saturable, low-affinity interaction with a slow off/on
rate.
• In general CD8+ T cells recognize endogenous antigens
and CD4+ T cells recognize exogenous antigens.
• MHC molecules bind multiple peptides, however each T
cell only recognizes one peptide.
Antigen Recognition by T Cells
