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ANTIGENS

Things for today


Understand difference between antigen and

immunogen
Chemical nature of an immunogen
Factors affecting immunogenicity
Haptens
B-cell and T-cell epitopes

Vocabulary

a) Antigen (Ag) - a substance that reacts with the products of a

specific immune response.


A substance that can be recognised by the immunoglobulin receptor of

B cells, or by the T cell receptor when complexed with MHC, is called


antigen.

b) Immunogen - a substance that induces a specific immune

response.
c) Hapten - Haptens are small molecules which are

nonimmunogenic, thus could never induce an immune response


when administered by themselves but which can when coupled to
a carrier molecule.
Free haptens can react with the products of a specific immune

response. Haptens have the property of antigenicity but not


immunogenicity.

d) Epitope or Antigenic Determinant - the discrete sites of an

antigen that combines with the products of a specific immune


response.
e) Antibody (Ab) - a specific protein which is produced in response

Immunogenicity and Antigenicity


Immunogenicity is the ability to induce a

humoral and/or cell mediated immune


response:
Antigenicity is the ability to combine

specifically with the final products of the


above responses (i.e., antibodies and/or cellsurface receptors)

Chemical nature of
immunogen
Proteins (most potent immunogens)
Polysaccharides
Nucleic acids
Lipids (some glycolipids and phospholipids)

Humoral Branch- Proteins and

polysaccharides
Cell med. Branch- Proteins and lipids

Factors influencing immunogenicity

Factors

Contribution
of
immunogen

Contribution
of biological
system

Method of
administrati
on

immunogen
Foreignness-

is essential to immunogenicity because selfresponsive cells are eliminated during lymphocyte development,
leaving only cells that respond to non-self, so-called "foreign" epitopes.

Size
Bigger>Smaller

Chemical composition
Heteropolymers>homopolymers
Protein Antigens
Primary structure
--sequence determinants
Conformational
Secondary structure
determinants
Tertiary structure
Quarternary structure

Physical form

Particulate> Soluble

Degradability

Ag processing by Ag-presenting cells (APC)

L-amino acids and D amino acids

Immunogenicity: contribution of
biological system
Genetics
Species
Individual

Responders vs Non-responders
The

species or individuals may lack or have altered genes


that code for the receptors for antigen on B cells and T
cells or they may not have the appropriate genes needed
for the APC to present antigen to the helper T cells.

Age
Usually the very young and the very old have a

diminished ability to mount an immune response in


response to an immunogen.

Immunogenicity: method of
administration
Dose
There is a dose of antigen above or below which the

immune response will not be optimal.


Boosters

repeated administrations>single dose

Route
Subcutaneous >Intraperitoneal> Intravenous >

Intragastric

Adjuvant
Adjuvants (from Latin adjuvare, to help) are

substances that, when mixed with an antigen and injected


with it, enhance the immunogenicity of that antigen.

Mechanisms of adjuvants
Prolonged persistence of immunogen

molecules at the site of injection.


Enhancement of co-stimulatory signals.
Local inflammation is increased.
Stimulation of lymphocyte proliferation in a

non-specific manner.

Classification of Adjuvant

Muramul dipeptide of mycobacterium

Haptens
Many biologically important substances,

including drugs, peptide hormones, and


steroid hormones, can function as haptens.
Conjugates of these haptens with large
protein carriers can be used to produce
hapten-specific antibodies.
These antibodies are useful for measuring the
presence of various substances in the body.
human chorionic gonadotropin (HCG)
(Pregnancy test)

Haptens
Karl

Landsteiner

demonstrated specificity and also enormous diversity of epitopes immune system can rec

Epitopes
B-cell Epitopes
T-cell Epitopes

B-cell Epitopes

The ability to function as a B-cell epitope is

determined by
nature of the antigen-binding site on the

antibody molecules displayed by B cells.


Presence of hydrophilic amino acids on the
protein surface that are topographically
accessible to membrane-bound or free
antibody.
May contain sequential (continous) or
nonsequential (discontinous) amino acids.
located in flexible regions of an immunogen
and display site mobility.

Types of Epitopes
1.

Linear epitopes

continuous and found in native (nondenatured) and denatured proteins.


specificity depends upon primary sequence.
typical size is 5-6 subunits in length.

2. Conformational epitopes
Discontinuous (involve multiple subunits, often located far apart in the
primary sequence of the antigen molecule) and are thus found only in native
(globular) proteins.
Specificity depends upon conformation, or three-dimensional shape, which
is a combination of tertiary and quaternary structure ... supported by
primary and secondary structure, of course.
Typical size is hard to pinpoint, but sequences of up to 16 amino acids in
certain protein antigens have been shown to interact with their
complementary paratope.

T-cell Epitopes
Antigenic peptides recognized by T cells form

trimolecular complexes with a T-cell receptor


and an MHC molecule
Antigen processing is required to generate
peptides that interact specifically with MHC
molecules.
Epitopes recognized by T cells are often
internal.

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