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Any substance that is foreign to the body and has the ability to induce an immune response is known as ‘Antigen’. The ability of an antigen to induce a humoral and/or cell-mediated immune response is known as immunogenicity. Therefore, an antigen is more appropriately called an immunogen. In contrast, the ability of an antigen only to combine specifically with the final products of the immune responses such as antibodies is called antigenicity. These antigens are called incomplete antigens or haptens. Haptens cannot induce an immune response. However, if they are coupled with a carrier molecule, they become immunogenic. A very good example is, the original pregnancy test kit that utilizes anti-HCG antibodies. HCG hormone is a hapten and it has to be conjugated with carrier molecules to get anti-HCG antibodies.
Properties of Antigens
1. Foreignness: In order to induce an immune response, a molecule must be recognized as foreign or non-self by the host. An immune response (antibody) is not produced against self-antigen. The immunogenicity of an antigen increases with an increase in the degree of foreignness. Generally, the greater the phylogenetic gap between two species, the greater will be the immune response.
For example, Bovine serum albumin (BSA) isolated from a calf is not immunogenic when injected into a cow, but strongly immunogenic when injected into a rabbit.
2. Molecular mass: Generally, substances with a molecular mass less than 5000–10,000 Da are poor immunogens. In contrast, the most active immunogens tend to have a molecular mass of 100,000 daltons (Da).
3. Chemical composition and heterogeneity: Molecules must be complex and heterogeneous in composition in order to be immunogenic. For example, homopolymers are less immunogenic. On the other hand, heteropolymers are more immunogenic. Generally, proteins are the most potent immunogens with carbohydrates ranking second. In contrast, lipids and nucleic acids generally do not act as antigens unless they are combined with proteins or carbohydrates.
4. Susceptibility to antigen processing and presentation: The development of both humoral and cell-mediated immune responses requires the interaction of T cells with the antigen that has been processed and presented together with MHC molecules.
Properties of the biological (host) system that contribute to immunogenicity
Even if an antigen has properties that contribute to immunogenicity, its ability to induce an immune response will depend on certain properties of the biological system/host that the antigen encounters.
1. Genotype of recipient host: The genotype or genetic constitution of an immunized host influences the type and degree of the immune response.
For example, A study has shown that two strains of mice responded differently after exposure to a synthetic immunogen. One strain produced a high immune response while another strain produced a low immune response. When they were crossed, the F1 generation showed an intermediate immune response.
2. Dose of administration: The dose of antigen determines the amount of antibody produced in the immunized host. An insufficient dose of antigen will not stimulate immune response either because it fails to activate enough T and B-lymphocytes or because of immunological tolerance in some cases. Conversely, an excessively high dose can also induce tolerance.
Further, a single dose of most immunogens will not induce a strong immune response. Rather, repeated administration over a period of weeks is required. Such repeated administration is called boosters. These booster doses allow the activation of T-cells and B-cells for a long time and antibodies are produced in greater amounts. This is the principle behind booster doses of vaccination.
3. Route of administration: The administration route strongly influences which immune organs and cell populations will be involved in the response. The immunogens are generally administered parenterally that is, by routes other than the digestive tract. The subcutaneous route is frequently used for the administration of immunogens as it moves first to local lymph nodes and activates T cells and B cells. Intravenous is preferred for soluble antigens without any adjuvant.
4. Adjuvants: Adjuvants are substances that when mixed with an antigen and injected with it, enhance the immunogenicity of that antigen. Adjuvants are often used in research and clinical trials to increase the immunogenicity of antigens that have immunogenicity or are available in low amounts.
The Best example is aluminum potassium sulphate or alum.
Example for water-in-oil adjuvants: Freund’s complete and incomplete adjuvant
References:
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Kelly, J., 1992. Immunology: by Janis Kuby, WH Freeman.
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