ANTIGEN AND ANTIBODY

An infectious agent, whether a bacterium, fungus, virus, or parasite, contains an

abundance of substances capable of inducing an immune response. These are called
immunogens or antigens.

Specifically, an immunogen is a sub- stance capable of stimulating B cell, T cell, or

both limbs of the immune response

An antigen is a substance that reacts with the products of an immune response

stimulated by a specific immunogen, including both antibodies and/or T lymphocyte
receptors

The “traditional” definition of antigen more correctly refers to an immunogen

A complete antigen is one that both induces an immune response and reacts with the
products of it, whereas an incomplete antigen or hapten is unable to induce an immune
response alone but is able to react with its products, e.g., antibodies. Haptens could be
rendered immunogenic by covalently linking them to a carrier molecule.

Following the administration of an antigen (immunogen) to a host animal, antibody

synthesis and/or cell-mediated immunity or immunologic tolerance may result. To be
immunogenic, a substance usually needs to be foreign, although some autoantigens
represent an exception. They should usually have a molecular weight of at least
10,000 kDa and be either proteins or polysaccharides. Neverthe- less, immunogenicity
depends upon the genetic capacity of the host to respond rather than merely depending
upon the antigenic properties of an injected immunogen.

The specific parts of antigen molecules that elicit immune reactivity are known as
antigenic determinants or epitopes.

a hapten is a relatively small molecule which by itself is unable to elicit an immune

response when injected into an animal but is capable of reacting in vitro with an
antibody specific for it. However, a hapten may be covalently linked to a carrier
macromole- cule such as a foreign protein that renders it immunogenic, and can form
new antigenic determinants

An antigenic determinant (Figure 3.1) interacts with the specific antigen-binding site
in the variable region of an antibody molecule known as a paratope

The excellent fit between epitope and paratope is based on their three- dimensional
interaction and noncovalent union. An anti- genic determinant or epitope may also
react with a T cell receptor for which it is specific

A single antigen molecule may have several different epitopes. Whereas an epitope
interacts with the antigen binding region of an antibody molecule or with the T cell
receptor, a separate region of the antigen that combines with class II MHC molecules
is known as an agretope.
An antigen molecule has two or more epitopes (or anti- genic determinants) per
molecule. Epitopes consists of approximately six amino acids or six monosaccharides.
Epitopes that stimulate a greater antibody response than others are referred to as
immunodominant epitopes.

The principal chemical features of antigens include their large size, complexity, and
ability to be degraded by enzymes within phagocytes. Most antigens are of 10,000
kDa or greater molecular weight. Exceptions include such substances as insulin with
5700 kDa

Antigenicity is usually more easily demonstrated with molecules of greater molecular

weight

However, size alone does not make the molecule antigenic. It must have a certain
amount of internal structural complexity.

Linear polymers of polylysine comprised of a repeating simple structure are not

antigenic. The majority of protein antigens contain 20 different amino acids in an
assorted arrangement.

Oligosaccharides com- prised of both monosaccharides and complex sugars are

antigenic.

The antigen must also be degradable by phagocytes to be antigenic. Antigen

processing includes enzy- matic digestion to prepare soluble macromolecular antigen.

Substances such as D-amino acid polypeptides that cannot be degraded in phagocytes

are not antigenic even though they might otherwise possess the characteristics of anti-
gens

Foreignness is another characteristic that is critical for antigenicity

We do not respond to our own self-anti- gens because we are immunologically

tolerant of them.

During development, the body becomes tolerant of self- antigens as well as foreign
antigens that may have been artificially introduced into the host prior to development
of the immune system

In general, T cells are rendered tolerant with lower doses of antigen and for longer
periods of time than are B cells. B cell tolerance is for relatively brief duration and
requires much greater quantities of antigen than does T cell tolerance. Tolerance is a
type of antigen-induced specific immunosuppression and antigen must remain in
contact with immunocompetent cells for the tolerant state to be maintained.

Tolerance induction is favored by the route of administration and the physical nature
of the injected antigen
For example, the intravenous route of injection of solubilized antigen favors tolerance
induction. By contrast, the injection of antigen in particulate form into the skin favors
the development of immunity. An antigen that induces tolerance is often referred to as
a tolerogen.

To mount an immune response to an antigen, a host must have appropriate immune

response (Ir) genes. This has been proven in animal studies in which inbred strain-2
guinea pigs were shown to be responders whereas strain-13 were not. Lymphocyte
proteins in man encoded by Ir genes include the class II MHC molecules designated
DP, DQ, and DR that are found on human B cells and macrophages. This enables
recognition among B cells, T cells, and mac- rophages. Antigens may be classified as
either T cell depen- dent (TD) or T cell independent (TI). As shown in Figure 3.1, TD
antigens are much more complex than TI antigens, are usually proteins, stimulate a
full complement of immunoglobulins with all five classes represented, elicit an
anamnestic or memory response, and are present in most pathogenic microorganisms.
This ensures that an effective immune response can be generated in a host infected
with these pathogens. By contrast, the simpler TI antigens are often polysaccharides
or lipopolysaccharides that elicit only an IgM response and fail to stimulate an
anamnestic response compared with T cell dependent antigens.