Immunology

Immunology is the study of immunity which is the protection from foreign (nonself) substances in the environment. The foreign substances are called "antigens" and include microbes, external proteins and polyscaccharides.

Immunogenicity is the ability to induce a humoral and/or cell mediated immune response. Although a substance that induces a specific immune response is usually called an "antigen" the more proper term is an "immunogen."  Factors which influence immunogenicity include the following:

• composition and size:  Proteins function as the most potent immunogens, with polysaccharides ranking second. In contrast, lipids and nucleic acids generally do not serve as immunogens unless they are complexed to proteins or polysaccarides. Large insoluble macromolecules generally are more immunogenic than small, soluble ones because the larger molecules are more readily phagocytosed and processed.

• foreignness: In order to elicit an immune response, a molecule must be recognized as nonself. The ability to recognize self molecules is thought to arise during development by exposure of immature lymphoctyes to self-components. Any molecule that is not exposed to immature lymphoctyes during this critical period is later recognized as nonself, or foreign, by the immune system.

• dose and route: Immunogen dosage and route of administration also affect immune response. A dose may be too small or too large to induce an immune response. An insufficient dose will not stimulate an immune response either because it fails to activate enough lymphocytes or because certain ranges of low doses can actually induce a state of tolerance in some cases. An excessively high does can also induce tolerance. A single dose of most experimental immunogens will also not induce a strong response. Repeated administration or "boosters" over a period of weeks is required to stimulate a strong response. Experimental immunogens generally are administered parenterally (routes other than the digestive tract) as by intravenous, intradermal, subcutaneous, intramuscular and intraperitoneal routes. Antigen administered intravenously is first carried to the spleen, whereas antigen administered subcutaneously moves first to local lymph nodes. The route of antigen injection determines which immune organs and cell populations will be involved in the response.

• Adjuvants or substances which when mixed with an antigen enhance the immunogenicity of that antigen are often used to boost the immune response. Some adjuvants prolong the persistence of antigen in the immunized animals. For example, when an antigen is mixed with aluminum potassium sulfate (alum), the salt precipitates the antigen resulting in a slower release of antigen from the injection site. Freund's water in oil adjuvants also function in this way. Freund's complete adjuvant, which contains heat killed Mycobacteria in the water in oil emulsion, is more potent than the incomplete form because a muramyl dipeptide component of the mycobacterial cell wall activates macrophages, increasing production of interleukin 1 and thus augments the immune response by activating T_H cells.

CD40, CD80, CD86 upregulation. In addition to Trif pathway leading to upregulation costimulatory proteins, must be an additional pathway for TLR3.

• genotype of an immunized animal also influences the type of immune response the animal manifests. MHC gene products which function to present processed antigen to T cells play a central role in this variety. The response of an animal is also influenced by the genes that encode B-cell and T-cell receptors and by genes that encode various proteins involved in immune regulatory mechanisms. Genetic variability in all of these genes affects the immunogenicity of a given macromolecule in different animals.

Antigencity is the ability of an antigen simply to interact specifically with free antibody and/or with antigen binding receptors on lymphocytes. Although all molecules possessing the property of immunogenicity also possess the property of antigenicity, the reverse is not true. Some small molecules called haptens possess the property of antigenicity but are not capable by themselves of inducing a specific immune response.

The two types of immune responses that the human body can mount against foreign pathogens are called (1) innate immunity and (2) adaptive immunity. Adaptive or acquired immunity is further classified into two broad responses called (1) humoral and cellular immunity. The development of both humoral and cell mediated immune responses requires interaction of T_H cells with antigen that has been phagocytosed, processed, and presented in association with MHC molecules on the surface of macrophages or other antigen presenting cells. Thus macromolecules that cannot be degraded and processed by antigen presenting cells are poor immunogens. For example, polymers of D amino acids, which are stereoisomers of L amino acids are poor immunogens because the degradive enzymes within macrophages can only degrade proteins containing L amino acids.