Immunogens and Antigens The compound that evokes the response is referred to as antigen or as immunogen. Antigen is any agent capable of binding specifically to components of the immune response e.g. B cell receptor (BCR) or B lymphocytes and soluble antibodies. An immunogen is any agent capable of inducing an immune response and is therefore immunogenic. All immunogens are antigens, but not all antigens are immunogens. A hapten is a compound that by itself, is incapable of inducing an immune response but against which an immune response can be induced by immunization with the hapten conjugated to a carrier. The immune response is directed against various parts of the conjugate including the hapten which can bind antibody molecules.

Requirements for Immunogenicity 1- Foreigness Animals normally do not respond immunologi-cally to self. The more foreign the substance, the more immunogenic it is. In exceptional cases autoimmunity is formed, the immune response is directed against his or her own tissues. 2- High Molecular weight Small compounds with a M. wt. < 100 Da "e.g. penicillin, aspirin, progesterone" are not immunogenic. Compounds of M. wt. between 1000-6000 Da "e.g. insulin, ACTH" may or may not be immunogenic. Those of M. wt. > 6000 Da "e.g. albumin" are generally immunogenic.

3- Chemical Complexity Simple molecules such as homopolymers of amino acids "e.g. a polymer of lysine with a M. wt. of 30,000 Da" are seldom good immunogen. Copolymers of several amino acids e.g. polyglutamic, alanine and lysine tend to be highly immunogenice.  4- Degradability Antigens that activate T cells to stimulate immune response must interact with MHC molecules expressed on APCs. APCs must first degrade the antigen through antigen processing "enzymatic degradation of antigen" before they can express epitopes on their surface. These epitopes stimulate the activation and clonal expansion of antigen-specific effector T cells. D-amino acids are resistant to enzymatic degradation and are not immunogenic. L- isomers are susceptible to enzymes and are immunogenic. Carbohydrates are not processed or presented, they are unable to activate T cells, but they activate B cells.

5- Further Requirements for Immunogenicity The genetic makeup "genotype". Genetic control of immune response is controlled by gene mapping within the MHC. The presence of antigen-specific B and T cells. 6- Dosage and Route of administration Repeated administration of antigen stimulates a strong immune response. Insufficient doses of antigen may not activate enough lymphocytes or because such a dose renders the responding cells uresponsive "tolerance". Subcutaneous administration of antigen elicit the strongest immune responses. Langerhans cells process and present antigen to effector cells. I.V administered antigens are carried to the spleen where they may induce tolerance or If presented by APCs generate and immune response. G.I.T route elicits local antibody responses within the intestinal lamina propria but often produce a systemic state of tolerance. Administration of antigen via intranasal route "respiratory tract" often elicits allergic responses.

Antigenicity and Antigen-Binding Site An immune response induced by an antigen generates antibodies or lymphocytes that react specifically with the antigen. The portion of the antibody that specifically binds to the epitope is concentrated in several hypervariable regions of the molecule which form the complementarity-determining region "CDR". The size of the epitope that combines with the CDR on a given antibody is approximately equivalent to 5-7 amino acids. Epitope binds to TCR "8-12 amino acids" is no covalently associated with MHC proteins of APC. A trimolecular complex is formed "TCR-epitope-MHC"

Major Classes of Antigens 1- Polysaccharides Immunogenic when associated with protein carries. Glycoproteins are good immunogens. ABO blood groups which are polysaccharides on the surface of the RBCs are examples of antigenicity of polysaccharides. 2- Lipids Lipids are rarely immunogenic. Lipoproteins, glycolipids are immunogenic.

3- Nucleic Acids They are poor immunogens. Nucleoproteins are good immunogens. In SLE anti-DNA antibodies are formed.  4- Proteins All proteins are immunogenic. Complex proteins are more immunogenic because they contain multiple epitopes.

Cross reactivity Toxin and Toxoid A toxin that has been modified to loose its toxicity but retains its immunogenecity is called toxoid. Toxoid is used for immunization. Toxoid cross reacts immunologically with toxin. Many epitopes in the toxoid are still reactive. When the antigen used for immunization is different form the one with which the induced immune components are then allowed to react, the terms homologous and heterologous are used. Homologous denotes that the antigen and the immunogen are the same. Heterologous denotes that the substance used to induce the immune response is different from the substance that is then used to react with the products of the induced response.

Cross reacting compounds share antigenic determinants. Some cross-reacting substance are unrelated to each other except that they have one or more epitopes in common. These substances are referred to as heterophile antigens. e.g. human blood group B antigen reacts with antibodies to certain strains of E. coli. The antigens of the microorganisms are referred to as heterophile antigens with respect to the blood group antigen.

Adjuvants: An adjuvant is a substance that when mixed with an immunogen, enhances the immune response against the immunogen. An adjuvant does not confer immunogenecity on haptens.  Adjuvant mechanisms include: increasing the biological or immunological half-life of vaccine antigens. increasing the production of local inflammatory cytokines. Improving antigen delivery and antigen processing and presentation by APCs. Adjuvants containing microbial components e.g. mycobacterial extracts are the best adjuvants.