DEFINITIONS:

1. ANTIGEN
Any agent capable of binding specifically to components of the
immune system;

Such as the BCRs on B lymphocytes and soluble

antibodies.

An antigen can also be defined as a substance that can be

recognized by the Ig, receptor of B cells or by TCR when
complexed with MHC molecule.
 Classification of antigens
i. Auto-antigens:
 Are self antigens that can lead to auto-immune
diseases.
 e.g. rheumatoid arthritis, auto-immune glomerulonephritis, etc.

ii. Endogenous antigens:

 Are those antigens produced by intracellular pathogens
e.g. viral and intracellular bacterial infections.
 The processed peptides are complexed with MHC-I
molecules and presented to CD8+ T cells on the surface of
APC
iii. Exogenous antigens:
Are antigens derived from extracellular organisms.
They enter the body from the outside, through inhalation,
ingestion, or injection.
They are endocytosed or phagocytosed by APCs.

Fragments presented to CD4+ T cells complexed to class II MHC-

II molecules.

.
iv. Hetero
antigens:
 Are antigens derived from one species of animal/organism that
induce immune response in another species/host.
 Corresponding antibodies produced are called hetero-antibodies.
v Alloantigens:
Are antigens that differ within a species.
 The corresponding antibodies produced are called alloantibodies.
E.g. the blood incompatibility antigen, rhesus factor antigen, etc
 Super antigens(SAGs)
 Proteins produced by pathogens & Not processed by APCs.

 Intact protein binds to variable region of β chain on TCR of T

cells and to MHC class II on APCs.

 They induce massive T cell activation. Large numbers of

activated T cells release large amount of cytokines leading to
systemic toxicity and skin syndrome diseases.
 Exa: Staphylococcal enterotoxins & Staphylococcal toxic
shock syndrome toxin-1 (TSST-1)

SAGs and diseases:

 Staphylococcal toxic shock syndrome .
 Staphylococcal scalded skin syndrome
 Immunogens vs Antigens
 A compound that evokes an immune response is referred to
either as antigen or as immunogen.
 The distinction between these terms is functional;
Immunogens are Ags capable of binding with immune receptor
(BCR/soluble Ab) & inducing immune response.
By contrast, an antigen is any agent capable of binding
specifically to components of the immune system, (BCR on B
lymphocytes and soluble antibodies).
 Thus all immunogens are antigens, but not all antigens are
immunogens
Hapten
 Is a low-molecular- weight antigen capable of binding with immune
receptor &without inducing immune response.
 In other words, they are antigenic but not immunogenic.
 BUT can produce immune response when conjugated with large
carrier molecule.

 Penicillin is a good example of a hapten.

The drug is not immunogenic by itself, but some people
develop hypersensitivity reaction to it.
In these people, when penicillin combines with serum
protein, the resulting combined molecules initiate an immune
reaction
 A hapten is a molecule too small to stimulate antibody formation by itself.

 However, when the hapten is combined with a larger carrier molecule, usually a
serum protein, the hapten and its carrier together function as an antigen and can
 Epitopes/ Antigenic Determinants
 An epitope is a small part on an antigen that binds with BCR &
TCR or soluble antibodies.

 The complementary antibody combining site is termed paratope,

concentrated in several HVR of the molecule, which form the CDR

 The number of epitopes on the surface of an antigen is its valence.

 Thus the antigen may be monovalent if it has one epitope or

multivalent if it has several epitopes.
In the antigen molecule, an epitope may be dominant or latent

The noninformation part of the antigen molecule is called a carrier, and is

required for any antigen to be complete
Epitope
 DETERMINANTS OF IMMUNOGENICITY
 Antigens vary widely in degree to which they are immunogenic.

 Immunogenicity is determined primarily by following factors:

Recognition of foreignness:
 To be immunogenic, molecules must be recognized as foreign
(“non-self”).
The more foreign a molecule the better its antigenicity.
Compounds that are part of self are not immunogenic to that
individual (exception autoimmunity)
 For example, if a rabbit is injected with its own serum albumin,
it will not mount an immune response. It recognizes the albumin
as self.

 By contrast, if rabbit serum albumin is injected into a guinea

pig, the guinea pig recognizes the rabbit serum albumin as
foreign and mounts an immune response against it.
Molecular size.
Relatively small substances have decreased immunogenicity
whereas large substances have increased immunogenicity

 Molecules with a molecular weight less than 1000 Da (e.g.,

penicillin, progesterone, aspirin) are not immunogenic

 Those of molecular weights between 1,000 and 6,000â•›Da (e.g.,

insulin, adrenocorticotropic hormone [ACTH]) may or may not
be immunogenic;

 And those of molecular weights greater than 6,000â•›Da (e.g.,

albumin, tetanus toxin) are generally immunogenic.
Chemical nature
Generally, proteins are more immunogenic than polysaccharides
which are in turn, more immunogenic than lipids and nucleic acids

Chemical complexity:
 Molecules with more complex chemical structure are better
antigens than simple polymers. E.g. amino acid homopolymers are
less immunogenic than heteropolymer amino acids.

 Each of the four levels of protein structure contributes to the

molecule’s immunogenicity.For example, antibodies can recognize
various structural features of a protein, such as its primary
structure
Structural stability:
 Structurally stable molecules are easily recognized by
immunocytes, but unstable substances such as gelatin are poor
antigens.
Genetic constitution of the host:
 Because of differences in MHC alleles, two strains of the same
species of animal may respond differently to the same antigen.
 The species or individuals may lack or have altered genes that
code for the antigen receptors on B cells and T cells, MHC
molecules & various immune regulatory proteins
Degradability:
 APCs must first degrade the antigen enzymatically before they
can express antigenic epitopes on their surface.
 Peptides composed of D-amino acids, which are resistant to
enzymatic degradation, are not immunogenic, whereas their L-
isomers are susceptible to enzymes and are immunogenic.
Dosage and Route of Administration
Dose
 There is usually a dose of antigen above or below which the
immune response will not be optimal,
 An insufficient dose will not stimulate an immune response
either because it fails to activate enough lymphocytes or
because it induces immunological tolerance

 Conversely, an excessively high dose can also induce tolerance.

 A single dose of most experimental immunogens will not induce

a strong response; repeated administration (boosters) over a
period of weeks is required.
This increases the clonal proliferation of antigen-specific T
cells or B cells
(b) Route of administration;
 Route strongly influences which immune organs and cell
populations will be involved in the response.

 Antigen administered intravenously is carried first to the spleen,

whereas antigen administered subcutaneously moves first to
local lymph nodes

 Major routes of administration include:

IV , ID , SC , IM, Intraperitoneal (ip)
Age
Age can also influence immunogenicity.

Usually the very young and the very old have a diminished
ability to mount an immune response to an immunogen
Administration of immunogen with Adjuvants
 Adjuvants enhance the immune response to an immunogen.

 They boost the immune response when an antigen has low immunogenicity
or when only small amounts of an antigen are available.

 Adjuvants exert one or more of the following effects;

Antigen persistence is prolonged
Co-stimulatory signals are enhanced
Local inflammation is increased
The nonspecific proliferation of lymphocytes is stimulated
Examples include:
 Aluminum potassium sulfate (alum) and Freund’s adjuvants
prolongs the persistence of antigen.
This results in a slower release of antigen from the injection site, so
that there is effective time of exposure to the antigen increases.

 Alum and Freund’s adjuvants also stimulate a local, chronic

inflammatory response that attracts both phagocytes and
lymphocytes leading to formation of a granuloma
Macrophages in a granuloma are activated, and this mechanism
enhances the activation of Thcells

.
Adjuvant mechanisms include:
(1) increasing the biological or immunological half-life of vaccine
antigens;
(2) increasing the production of local inflammatory cytokines; and
(3) Improving antigen delivery and antigen processing and
presentation by APCs, especially the dendritic cells.

Adjuvants are classified into;

Inorganic adjuvants: include aluminium salts (aluminium
phosphate & aluminium hydroxide), commonly used in human
vaccines
 Organic adjuvants: Organic compound is also more commonly
used in animal vaccines
 Oil-based adjuvants: Commonly used in some veterinary
vaccines
 Virosomes : Contain a membrane-bound hemagglutinin and
neuraminidase derived from the influenza virus, and serve to
facilitate the uptake of immunogen into APC

End
REFERENCES
From Basic to Clinical Immunology
Vladimir V. Klimov

KUBY IMMUNOLOGY

IMMUNOLOGY A Short Course- SEVENTH EDITION

Richard Coico & Geoffrey Sunshine

Textbook of Immunology
Sunil Kumar Mohanty MD