ANTIGEN

Dr. Soumya Dasgupta

 Antigen: substances that can stimulate an immune
response and, given the opportunity, react specifically by
binding with the effector molecules (antibodies) and
effector cells (lymphocytes).
 Immunogen: A substance that challenges the immune
system and can initiate an immune response.
 Antigenicity: The property that allows a substance to
combine specifically with antibodies or TCRs, whether or
not they are immunogenic.
 Immunogenicity: The ability to induce Humoral and/or
Cell mediated immune response.
TYPES OF ANTIGEN
antigens may be classified into different types
depending on two attributes :
 Immunogenicity- ability of inducing an immune
response
 Immunological reactivity- specific reaction with
antibodies or sensitized cells
TYPES OF ANTIGEN
 Complete Antigen : able to induce antibody formation and
produce a specific and observable reaction with antibody so
produced.

 Haptens :
- low molecular weight substances
- they are not immunogenic
- can induce immune response when covalently coupled to a
large protein molecule, called the carrier molecule.
Types of Haptens
Haptens may be simple or complex.
1. Simple haptens:
 Simple haptens are nonprecipitating.

 They can inhibit precipitation of specific antibodies by the

corresponding antigen or complex hapten.
 Simple haptens are univalent, since it is assumed that
precipitation requires the antigen to have or more antibody
combining sites.
2. Complex haptens: Complex haptens can precipitate with
specific antibodies, complex haptens are polyvalent .
EPITOPE
 Smallest unit of antigenicity
 Chemically, they include sugars, organic acids and bases,
amino acid side chains, hydrocarbons and aromatic
groups.
 sequential or linear epitope:

- Within a protein, an epitope may be formed by a specific

sequence
- may be present as a single linear segment of the primary
sequence
-T cells recognize sequential epitopes
conformational epitope:
-present as a three dimentional structure formed by bringing
together on the surface residues from different sites of the
peptide chain during its folding into the tertiary structure.
-Recognized by B cells

 Paratope: The combining area on the antibody molecule,

corresponding to the epitope
 Valence: The number of antigenic determinant sites on the
surface of an antigen is its valence. The valence determines the
number of antibody molecules that can combine with the
antigen at one time.
The antigen is monovalent or multivalent.
DETERMINANTS OF ANTIGENICITY

1. Size
2. Chemical nature
3. Foreignness
4. Susceptibility to tissue enzymes
5. Antigenic specificity
6. Species specificities
7. Isospecificities
8. Autospecifity
9. Organ specificity
10. Heterogenetic (heterophile) specificity
1. Size (Molecular Weight) :
 Generally, large molecules are more antigenic.

 Molecules <5000 m.w are feeble antigens.

 Low molecular weight substances may be rendered antigenic

by adsorbing them on large inert particles such as bentonite or
kaolin.
 Exception:

- picryl chloride, formaldehyde and drugs such as aspirin,

penicillin and sulphonamides
- The reason for this appears to be that the complex of such a
substance, acting as hapten, with a tissue protein acting as a
carrier, forms a complete antigen.
2. Chemical Nature :
 In general, proteins are the best immunogens and
carbohydrates are weaker immunogens.
 Lipids and nucleic acids are poor immunogenic. Their
antigenicity is enhanced by combination with proteins.
 A certain amount of chemical complexity is required, e.g.
amino acid homopolymers are less immunogenic than
heteropolymers containing two or three different amino
acids.
 all proteins are not antigenic. Eg.- Gelatin
3. Foreignness : the greater the difference between the
antigen (Ag) and similar molecules in the host’s body, the
greater the immune response that is generated.

4. Susceptibility to Tissue Enzymes: Only those substances

which can be metabolized and susceptible to the action of
tissue enzymes behave as antigens.
-Phagocytes and intracellular enzymes appear to play an
essential role in breaking down antigens into
immunogenic fragments.
-Substances unsusceptible to the tissue enzymes such
as polystyrene latex are not antigenic.
-Substances that are insoluble in body fluid and not
metabolized are not antigenic.
-Substances very rapidly broken down by tissue
enzymes are also not antigenic.
-Polypeptides consisting of L-amino acids are
antigenic while synthetic polypeptides composed of
D-amino acids which are not metabolized in the body
are not antigenic.
5. Antigenic Specificity :
 Stereochemical; determined by single chemical groupings and
even by a single acid radical.
 Antigenic specificity varies with the position of antigenic
determinant, i.e. whether it is in ortho, meta or para positions.
 The influence of spatial configuration of the determining group
was shown by differences in antigenic specificity of the dextro,
levo and meso isomers of substances such as tartaric acid.
 Antigenic specificity is not absolute. In many cases an
antibody specific for one antigen may display significant cross-
reactivity for an apparently unrelated antigen.
5a. Species Specificity:
 Tissues of all individuals in a species possess species specific
antigens. Thus, human blood proteins can be differentiated
from animal proteins by specific antigen-antibody reaction.
 This immunological relationship parallels phylogenetic
relationships
 used in tracing relationships between species.

 Species- specific antigens also possess forensic applications in

the identification of species of blood and of seminal stains
 Phylogenetic relationships are reflected in the extent of cross-
reaction between antigens from different species that cause
hypersensitivity.
5b. Iso-specificity:
 Isoantigens or alloantigens are antigens found in some but
not all members of a species. These are able to produce
alloantibodies or isoantibodies in individuals who are free
from the antigens.

 Examples of Isoantigens
i. Human erythrocytes antigens: on the basis of which all
humans can be divided into different blood groups; A, B,
AB and O.
ii. Histocompatibility antigens: cellular determinants
specific to each individual of a species. Histocompatibility
typing is essential in organ/tissue transplantation from one
individual to another within a species.
5c. Autospecificity:
 Autologous or self-antigens are ordinarily
nonantigenic but there are exceptions.
 Certain self-antigens are present in closed system and
are not accessible to the immune apparatus and these
are known as sequestrated antigens. Eg. Lens protein.
 Antigens that are absent during embryonic life and
develop later are also not recognised as self antigen.
Eg. Sperm.
5d. Organ Specificity :
 Some organs such as brain, kidney and lens protein of
different species, share the same antigens. These
antigens are known as organ-specific antigens,
characteristic of an organ or tissue and found in different
species.

 Injection of heterologous organ-specific antigens may

induce an immune response damaging the particular
organs or tissue in the host.

 Example : The neuroparalytic complications following

antirabic vaccination using sheep brain vaccines
6. Heterogenetic (Heterophile) Specificity:
Same or closely related antigens occurring in different
biological species, classes and kingdoms are known as
heterogenetic or heterophile antigens.
Examples :
 Forssman antigen: lipid carbohydrate complex widely
distributed in man, animals, birds, plants and bacteria. It
is absent in rabbits.
 Weil-Felix reaction: Diagnosis of Rickettsial infection
based on Cross-reaction between O antigen of
OX19,OX2, OXK strains of Proteus and certain
rickettsial antigens .
 Paul-Bunnell test: During infectious-mononucleosis
heterophile antibodies appear in the serum of the patient.
These antibodies agglutinate sheep erythrocytes.

 Cold agglutinin test: Agglutination of human O group

erythrocytes at 4°C by the sera of patients suffering from
primary atypical pneumonia.

 Agglutination of Streptococcus MG: Agglutination of

Streptococcus MG by the sera of the patients of primary
atypical pneumonia.
 TOLEROGENS

 Antigens do not always exhibit immunogenicity

or evoke antibody formation.
 An antigen presented at one concentration might
induce specific immunological unresponsiveness
or tolerance in some instances, while at another
concentration it might promote immunity.
 An antigen that induces tolerance is referred to
as tolerogen.
Types of Tolerance:

 A. Natural Tolerance: The nonresponse to self-

molecules is due to natural tolerance and it appears
during fetal development when the immune system is
being formed.

 B. Acquired Tolerance : Acquired tolerance arises when

a potential immunogen induces a state of
unresponsiveness to itself.
 BIOLOGICAL CLASSES OF ANTIGENS

Depending on their ability to induce antibody

formation, antigens are classified as
- T cell dependent (TD) antigens
- T cell independent (TI) antigens

T cell dependent (TD) antigens:

 Most natural proteins

 B cells cannot respond to them without co

stimulatory signal from TH cells.
T dependent responses rely on T cells and their
products to control the antibody class, affinity
and memory.
 They induce the full gamut of immunoglobulin
isotypes—IgM, IgG, IgA and IgE.
 They produce immunological memory, require
preliminary processing and are rapidly
metabolized in the body.
T cell independent (TI) antigens: can directly
stimulate antibody production by B cells without
apparent participation of T cells.
 Most microbial lipids, sugars and some nucleic
acids are TI antigens.
 The immune response generated to these
antigens tends to be similar on each exposure,
i.e. IgM is the antibody and the response shows
little memory.
 Two types:
Type 1: directly mitogenic for B cells and cause
polyclonal B cell activation. Eg. LPS, endotoxin.
Type 2: activate B cells to generate specific
antibodies with the help of cytokines and
complement other cells of immune response. Eg.
Pneumococcal capsular polysaccharide.
 Properties TD antigens TI antigens
T cell involvement Yes No
Antigen interaction Involves Tertiary Involves Binary
complexes of T cell complexes of
receptor, Ag, MHC membrane Ig and Ag
Ag processing by yes no
macrophages
Chemical nature Mostly soluble protein Type 1: LPS
Type 2 : polymeric
protein and
polysaccharide
Degradability easy Type 2: poor
Complement activation no Type 2
Immunologic memory yes no
Polyclonal activation no Type 1
Antibody production Full range IgM and IgG3
Isotype switching yes Type1: no
Type2: limited
 SUPERANTIGENS
bacterial proteins which can interact with antigen-
presenting cells (APCs) and T cells in nonspecific
manner.
 Activate very large number of T cells irrespective of
their antigenic specificity.
 Medium sized ( 22-29 kDa) proteins characterized by
high resistance to proteases and to denaturation by CD4+
T cells.
 They causes release of cytokines ( IL 2) which results in
massive proliferation of T cells, which leads to further
release of a variety of cytokines.
Organism Superantigen Disease
Staphylococcus aureus enterotoxin Food poisoning, toxic
shock syndrome
Gr A Streptococci Pyrogenic exotoxin Shock, rheumatic fever
HIV negative regulatory AIDS
factor (nef)
Rabies virus Nucleocapsid protein Rabies
DETERMINANTS RECOGNIZED BY
INNATE IMMUNE SYSTEM:
 The receptors of adaptive immune system recognise
discrete determinants and demonstrate a high degree of
specificity, enabling this system to recognise and react to
a particular pathogen.
 Components of innate immune system recognise unique
molecular patterns which are shared by many related
pathogens but not with their host. (Pattern recognition)
 The broad molecular patterns are called: Pathogen
associated molecular pattern (PAMP )
 Receptors for PAMP are Pattern recognition receptors
( PRR )
PRRs are of 3 types:
1. Toll like receptors:
 transmembrane receptors present on macrophages and
dendritic cells.
 13 types.

2. Scavenger receptors: CD36, CD68, SRB 1

3. Mannose receptors: on the surface of phagocytes.

Thank you