Antigen

Lectures outlines

1.Definitions.

2.Classification of antigens.

3.Factors Influencing Immunogenicity.

Contribution of the immunogene.

Contribution of the biological system.

4.Antigenic epitopes.

5.Adjuvants.
1. Definitions

Antigens: are substances that induce a specific immune

response and subsequently react with the products of a
specific immune response.

The word originated from the fact that they can stimulate

antibody generation.
 Self vs non-self proteins
• Antigen: any substance capable of provoking an immune
response; molecules not normally present in the body;
non-self

• MHC protein – major histocompatibility complex

proteins appear on every cell in our body; its presence
defines self.
MHC proteins include small sections of other body proteins

• MHC “presents” small

pieces of protein on the

surface of every cell in

human body
 2. Classification of antigens: They can be classified
according to their origin:
I. Exogenous antigens

Exogenous antigens are antigens

that have entered the body from

the outside, for example by

inhalation, ingestion, or injection.

These antigens are taken into the

antigen-presenting cells (APCs),
processed into fragments, and
presented by MHC II
II. Endogenous antigens

Endogenous antigens are

antigens that have been
generated within the
cell, as a result of cell
metabolism, or because
of viral or intracellular
bacterial infection.
III. Autoantigens

An autoantigen is usually a normal protein or

complex of proteins (and sometimes DNA or

RNA) that is recognized by the immune system

of an individual as non-self.
IV. Tumor antigens

Tumor antigens are those antigens that are presented by

the MHC I molecules on the surface of tumor cells.

Types of tumor associated antigens

1) Viral Antigen:

a- Viral proteins and glycoproteins.

b- New antigens produced by virally infected host

cells under control of viral nucleic acid.

 Types of Tumor Associated Antigens

2) Tumor specific antigens:

- Tumor cells develop new antigen specific to

their carcinogens.

3) Tumor specific transplantation antigens:

- Tumor cells express new MHC antigens due to

alteration of normally present MHC antigens.

4) Oncofetal antigens:

a- Carcino-embryonic antigens (CEA).

- Normally expressed during fetal life on fetal gut.

- Reappearance in adult life:

GIT, pancreas, biliary system and cancer breast

b- Alpha fetoprotein:

- Normally expressed in fetal life.

- Reappearance in adult life; hepatic cancer

V. Superantigen

• Superantigens (SAgs): are microbial proteins of 22-29

Daltons in size and are potent stimulators of the
immune cells in an unconventional manner produced
by bacteria, virus and mycoplasma.
• Superantigens are among the most potent T-cell mitogen
known. They stimulate both T and B cells with effect on T
cell more profound.
• During SAg stimulation, large number of activated T-cells
generates a massive immune response.

• This immune response is not specific to any

particular epitope on the SAg.
• This in turn will undermining one of the fundamental
strengths of the adaptive immune system, the specificity.
The massive immune response generated by SAg is due to systemic release
of large amounts of cytokines especially TNF-which will lead to shock and
multiple organ failure.

SAg can be of two types:

Exogeneous
Variety of exotoxins secreted by
some Gram+ bacteria
Endogeneous
Cell membrane proteins encoded
by viruses
In normal antigen-induced T-cell response 0.001-0.0001% of the body’s T-
cells are activated; while in SAgs response 5-20% of the body’s T-cells
are activated. This causes a massive immune response.

Activation of 5-20% T cells

Massive cytokine
production
 Comparison between classical antigen response
and superantigen response

Classical Ag response Superantigen response

1- Requires processing by APC 1- Does not require processing by

APC

2- Antigen recognition and T-cell 2- Antigen recognition and T-cell

activation is MHC-II restricted activation is not MHC-II restricted.

3- Small proportion of T-cells (<0.001) 3- Massive T-cell activation (5-20% of

become activated and highly total T cells) and associated with

regulated response adverse consequences

Conventional Ag
VI. Mitogen
• An agent that induces mitosis.
Here means to activate T cells and/or B cells without help
from APCs.
• Examples:

a) Lectin, for example, concanavalin A (ConA).

b) LPS (lipopolysaccharide).

c) Staphylococcal protein A(SPA).

Antigens can also be classified according to their structure into:

I. Complete antigen (foreign protein, polysaccharides, lipids, and

nucleic acids).

II. Incomplete antigen, also known as hapten.

Hapten cannot induce immune response because it lacks one or

more features needed for this function.

Haptens (Incomplete Antigens) are:

• Small molecules (peptides, nucleotides, and hormones).

• Not immunogenic by themselves.

• Are immunogenic when attached to body proteins.

• Examples: poison ivy, animal dander, detergents, and

cosmetics.
 3. Factors Influencing Immunogenicity

Contribution of the Immunogen

i. Foreignness.
ii. Size.
iii. Chemical Composition.

– Primary Structure Sequence determinants

– Secondary Structure
– Tertiary Structure Conformational determinants
– Quaternary Structure
iv. Physical Form
– Particulate > Soluble

– Denatured > Native

v. Degradability
– Ag processing by Ag Presenting Cells (APC)

vi. Dose.

vii. Route.
– Subcutaneous > Intravenous > Intragastric

viii. Adjuvant
– Substances that enhance an immune response to an Ag
 Factors Influencing Immunogenicity

Contribution of the Biological System

1. Genetics
– Species
– Individual
• Responders vs Non-responders
2. Age
 4. Antigenic epitopes

Epitope, or, antigenic determinants, are the portions

of antigen molecules that physically interact with
paratopes (combining sites) of immune response
molecules.

epitope the part of an antigen molecule to which an

antibody attaches itself

F
e
 Types of Epitopes

a. Linear epitopes
continuous and found in polysaccharides as well as protein.

b. Discontinuous epitopes

Discontinuous (involve multiple subunits, often located far

apart in the primary sequence of the antigen molecule).

5. Adjuvant

• An adjuvant is a substance that helps and enhances the

pharmacological effect of a drug or increases the ability

of an antigen to stimulate the immune system.

 Classification of Adjuvant

• Freund’s adjuvant.
 Complete Freund’s adjuvant(CFA)

 Incomplete Freund’s adjuvant (IFA)

• Liposome.

• Inorganic compound.

• Cytokine.

• Biodegradable nanoparticles.
 Mechanisms of adjuvants action

• Prolonged persistence of immunogen molecules at the

site of injection.

• Enhancement of co-stimulatory signals.

• Stimulation of lymphocyte proliferation in a non-specific

manner.