Antigens are molecules that can be recognized by the immunoglobulin receptor of B cells or the T-cell receptor when complexed with the major histocompatibility complex (MHC). The term antigen is a shortened form of the words “antibody generator.” Antigens are substances that react with antibodies, whereas immunogens are molecules that induce an immune response. In most cases, antigens are immunogens, and the terms are used interchangeably. Haptens are antigens that are not immunogenic but can participate in immune reactions. The ability of an antigen to elicit an immune reaction in the form of a B-cell or T-cell response is referred to as immunogenicity, whereas antigenicity simply refers to the ability to combine specifically with the products of the above responses. All immunogenic molecules are also antigenic, but all antigenic molecules cannot be considered immunogenic. As a result, haptens are said to be immunogenic.
Determinants of Antigenicity
There are several factors that contribute to a substance’s immunogenicity. Antigenicity is determined by a variety of factors, including:
- Chemical-structural complexity
- Molecular size
- Other factors
Highly stable and nondegradable substances (for example, some plastics, metals, or D-amino acid chains) are not immunogenic. This is due to the fact that internalization, processing, and presentation by antigen-presenting cells (APCs) are always required for an immune response to be mounted. As a result, very stable substances (such as silicon) have proven to be effective as nonimmunogenic materials for reconstructive surgeries such as breast implants.
On the other hand, if a substance is very unstable, it may break up before an APC can be internalized, and hence become immunogenic. Furthermore, larger, insoluble complexes are immunogenic than smaller, soluble ones. This is because macrophages find it easier to phagocytose, degrade, and present the insoluble complexes than the soluble complexes.
2. Chemical-structural complexity
Polysaccharides are the most potent immunogens, followed by proteins. Although nucleic acids and lipids may act as haptens, they are ineffective at eliciting a good immune response. A protein’s structural complexity influences its immunogenicity. Chains of single amino acids or sugars are not immunogenic, but when different amino acids or sugars are combined in the same molecule, the immunogenicity is greatly increased.
The response of T cells to the peptide component of proteins in cell-mediated immunity is determined by how the peptide is recognized and presented by MHC cells. As a result, protein structure is important in immunogenicity, particularly in inducing cellular immunity.
Because lipid-specific antibodies are difficult to produce, they play a minor role in immunity. These antibodies, however, play a role in the detection of certain lipid-based molecules and drugs. These antibodies are created by first treating lipids with haptens and then conjugating them with appropriate carrier molecules, such as proteins (e.g., hemocyanin or bovine serum albumin).
A molecule must be recognized as nonself, i.e., foreign, in order to be immunogenic. The immune system classifies a molecule as self or nonself depending on whether it was exposed to the immune system during fetal development.
The ability of the host to tolerate selfantigens is implied by foreignness. Tolerance to self-antigens develops through contact with them during the early stages of immune system development, particularly during the development of lymphocytes.
In general, the greater the distance between two species, the greater the immunogenicity of a molecule from one species when exposed to that of the other. Bovine serum albumin, for example, is more immunogenic in chickens than in goats. A graft from an unrelated human will be rejected in about 2 weeks unless immunosuppressive drugs are used, whereas a chimp graft will be rejected in hours even if drugs are used. A kidney graft from an identical twin, on the other hand, will be readily accepted.
4. Molecular size
Protein molecules with a high molecular weight are generally antigenic. Substances with molecular weights of 100,000 Da or greater are highly immunogenic, whereas substances with molecular weights less than 5000 Da are generally not immunogenic. This property has been used in experimental studies to induce an immune response by using high molecular weight proteins such as bovine gamma globulin (MW 150,000 Da). Adsorption of low molecular weight substances on carrier particles such as bentonite, kaolin, and other inert particles can make them antigenic.
5. Other Factors
The following are list of other factors considered as determinants of Antigenicity
I. Biological system
The biological system is also important in determining an antigen’s immunological efficiency. Some substances are immunogenic to one person but not to another (i.e., responders and nonresponders). This is because individuals may lack or have altered genes that code for antigen receptors on B and T cells, or they may lack the appropriate genes required for the APC to present antigen to helper T (TH) cells.
II. Dosage and route of the antigen
The antigen’s immunogenicity is also influenced by the antigen’s dose and the route through which it comes into contact with the immune system. Antigen at very low doses does not stimulate immune response, either because too few lymphocytes are contacted or because a nonresponsive state is induced. A very high dose, on the other hand, does not produce tolerance.
Repeated antigen administration (booster doses) may be required to improve the host’s immune response to specific antigens. This is especially important in the case of vaccines, which require a certain level of immunity. As a result, booster doses of vaccines such as DPT (Diphtheria, Pertussis, Tetanus), DT (Diphtheria, Tetanus), and others are administered to ensure adequate antibody levels. To produce a high level of antibodies, antigens are typically administered parenterally. The antigens can be administered intravenously, subcutaneously, intradermally, intramuscularly, intraperitoneally, or mucosally. Subcutaneous administration is usually more effective than intravenous administration at eliciting an immune response.
Adjuvants are substances that, when mixed with an antigen and injected with it, increase the antigen’s immunogenicity. Adjuvants boost the strength and duration of the immune response. Adjuvants increase antigen immunogenicity in several ways:
- Adjuvants such as aluminum potassium sulfate (alum) and Freund’s water-in-oil adjuvant extend antigen persistence by forming a depot at the injection site. Alum precipitates the antigen and gradually releases it. The water-in-oil emulsion binds to the antigen and forms small droplets, which are released slowly over time.
- Freund’s complete adjuvant contains heat-killed mycobacteria in addition to the emulsifying factors. The bacterial components activate macrophages, increasing IL-1 production as well as the level of B7 membrane molecules, thereby improving the immune response. Increased expression of class II MHC improves APC’s ability to present antigen to TH cells. B7 molecules on the APC bind to CD28, a cell-surface protein on TH cells, resulting in costimulation, or T-cell immune response enhancement.
- Some adjuvants, such as synthetic polyribonucleotides and bacterial lipopolysaccharides, stimulate nonspecific lymphocyte proliferation and thus bring about their action.