Immunogens and Antigens

Introduction

Emphasize that we are talking about the "Acquired Immune Response"

antigen -- any agent (molecule) that binds to components of the immune response -- lymphocytes and their receptors -- antibodies and the TcR.

immunogen -- any agent capable of inducing an immune response.

This distinction is probably most clear when discussing the situation of a hapten and its carrier.

hapten -- is antigenic but not immunogenic unless it is attached to a carrier molecule of some sort which supplies the immunogenicity.

Requirements for Immunogenicity:

Foreignness -- note the example of the rabbit immunized with its own serum albumin vs. the rabbit immunized with guinea pig serum albumin.

How do you prove that the rabbit unable to respond to its own albumin is still immunocompetent?

Note also that it is possible for self "antigens" to be immunogenic. Thus the foreignness requirement can be overcome.  When this happens it results in autoimmunity.

High Molecular Weight -- note that these are general categories and that there are some exceptions. How could you make a small "non-immunogenic" molecule "immunogenic"?

Chemical Complexity -- What is meant by the term "homopolymer"? How can you make a non-complex molecule more complex?

Note the discussion about the immunogenicity of the different levels of protein complexity and its discussion in Fig. 3.1.

Degradability -- Most protein antigens need to be processed and presented by antigen presenting cells. The digested fragments become bonded to "MHC" proteins (or MHC antigens) on the surface of the APC and this whole complex then binds to T-cells.

Carbohydrate antigens are not processed or presented. They can bind to B-cells directly and activate them to produce antibody.

Other requirements for immunogenicity:

Genetics -- The number and quality of the genes for the MHC proteins vary in a population of animals and this will affect the ability of the individual animal to develop an immune response.

Individual animals can also vary with regard to their repertoire of T and B cell antigen receptors.

Dose and Route of the antigen -- Too low or too high a dose of antigen can actually induce a state of Tolerance or non-responsiveness in the animal.

The route of immunization can cause very different responses -- for instance antigens that come in contact with mucous membranes generally induce IgA antibodies, whereas intramuscular and intravenous immunization often induces IgG and IgM responses.

*Primary and Secondary Responses*

Please study Fig. 4.12 on page 51 which describes the kinetics of an antibody response to an one antigen.  Pay particular attention to the terms which are either in the figure, in the text or which are described in lecture:

priming immunization
primary response
secondary response
memory response
anamnestic response

This figure is intimately related to the clonal selection theory described in figure 1.1 on page 4.

Antigen Binding Site of the Antibody and the T-cell receptor:

Review the structure of the antibody molecule (Fig. 4.3, pg. 42).

Particularly note where variable regions of both the light chain and the heavy chains come together.

The antigen binding site is formed by the association of the V_Heavy and the V_Light domains.  Since these are protein domains it would follow that the conformation of these domains determines this antigen binding function.  Thus we should expect that particular amino acids in certain areas of the domain would play a large role in binding to antigen.

(See if you can figure out what they are trying to show you in Figures 4.4, 4.5 and 4.6. In these figures they are trying to diagram which amino positions actually bind to the antigen epitope in the binding site).

 
The section of the antigen which actually binds to the the antibody binding site is called the epitope of the antigen. This is also called the antigenic determinant of the antigen.

The antibody binding site is sometimes called the paratope or the idiotope or the idiotype.

Epitopes recognized by T-cells and B-cells

T- cells and B-cells can recognize and react to different epitopes even if they are on the same molecule!

Study table 3.1 on page 31.

Much of this table can be summarize by these simple statements:

B-cells recognize and bind to free antigen in solution.

 B-cell epitopes are exposed and easily accessible.

T-cells recognize and bind to antigen that has been processed and presented in the context of MHC on antigen presenting cells.

Major Classes of Antigens

Please read this over. Note that an immune response can be mounted to just about any kind of molecule. This has important implications for autoimmunity and tolerance.

Note also that the binding of epitopes to their paratopes is non-covalent.

*Cross-Reactivity*

This section starts off with a discussion about toxin and toxoid. What is the difference?

Then they go on to describe what is meant by cross-reacting antigens. Essentially what they are saying here is that there are many examples of totally unrelated antigens that have small parts or epitopes (or antigenic determinants) in common. Thus an immune response to one such antigen can cause the production of antibodies that react with the second antigen.

Such antigens can be call heterophile antigens.  Likewise, the antibodies made to such antigens are often called heterophile antibodies.

Please note the examples given with regard to:

human blood group A antigen and pneumococcal capsule polysaccharide

human blood group B antigen and E. coli polysaccharide antigens

I'd also like to mention the relationship between Streptococcus pygenes M-protein and human heart muscle

Antigenic similarity between Horse-red-blood cell antigens and Epstein-Barr Virus

Adjuvants

We'll have a short discussion about adjuvants.