The concept of antigen, antigenicity, and immunogenicity
Antigen — a genetically foreign substance capable of interacting with components of the immune system. However, the definition "a substance that causes an immune response" is not always correct because there are two independent properties of an antigen.
- Antigenicity — the ability of a molecule to bind to an antibody or an antigen-recognizing receptor.
- Immunogenicity — the ability to induce a full-fledged immune response.
These properties do not always coincide. A classic example is a hapten: a low-molecular-weight substance that binds to an antibody but does not trigger an immune response on its own. A hapten becomes immunogenic only after binding to a carrier molecule (carrier protein) to form a complete complex recognized by the immune system.
Classification of antigens by origin
- Autoantigens — the self-antigens of a given individual.
- Isoantigens — antigens of a genetically identical individual (such as an identical twin or inbred laboratory animals).
- Alloantigens — antigens of another individual of the same species.
- Xenoantigens — antigens of an individual of another species.
The further phylogenetically organisms diverge, the higher the immunogenicity of their antigens for the recipient.
Criteria of immunogenicity
- Foreignness — the degree of evolutionary divergence of the antigen source.
- Molecular weight — the optimal range is roughly 10–100 kDa; molecules that are too small or excessively large have poor immunogenicity.
- Particulate nature — particulate (cellular) antigens induce a response significantly more effectively than soluble ones.
- Chemical complexity — heteropolymers with a diverse structure are more immunogenic than simple monomers and homopolymers.
- Route of administration and dose — intravenous and parenteral routes are usually more effective than oral; the dose must be optimal, since excessively high doses can induce immunological tolerance instead of a response.
The epitope as the functional unit of an antigen
Antigenic determinant, or epitope, is the region of the antigen molecule directly recognized by an antibody or lymphocyte receptor. The rest of the molecule does not participate in recognition. A single antigen can contain several different epitopes, which determines the diversity of the lymphocyte clones it induces.
Thymus-dependent and thymus-independent antigens
T-dependent antigens make up the majority of antigens. To trigger antibody production by B lymphocytes, they require cooperation with T helper cells. They bind to both BCR (B lymphocyte receptor) and indirectly to TCR (T lymphocyte receptor) after processing, ensuring the formation of all immunoglobulin isotypes except IgD, the establishment of immunological memory, and antibody class switching. Their feature is a small number of heterogeneous epitopes within a large molecule.
T-independent antigens activate B lymphocytes without T cell help. They contain repeatedly occurring epitopes, which facilitates direct recognition by the B cell receptor. They are divided into two types:
- Type 1 — cause polyclonal activation of B lymphocytes (e.g., bacterial LPS).
- Type 2 — do not cause polyclonal expansion (capsular polysaccharides).
The response to them is represented predominantly by IgM and partially IgD, is not accompanied by class switching, and does not form immunological memory. Reactions to such antigens (cell wall lipopolysaccharides, repeating carbohydrate structures) are genetically determined and evolutionarily fixed.
Allergens
Allergen — an antigen that induces hyperproduction of IgE and the development of an allergic reaction (type I hypersensitivity). IgE is fixed by its Fc fragment to the surface of mast cells and basophils. Upon re-exposure, the antigen cross-links IgE molecules on the membrane, which leads to degranulation of the mast cell and the release of histamine, heparin, leukotrienes, and other mediators. Clinically, this manifests as edema, pain, bronchospasm, and other symptoms of immediate allergy.
Key points
- Antigenicity and immunogenicity are different properties: a hapten is antigenic, but not immunogenic without a carrier.
- By origin, antigens are divided into auto-, iso-, allo-, and xenoantigens.
- Immunogenicity is determined by foreignness, molecular weight, particulate nature, chemical complexity, route, and dose of administration.
- Epitope — a specific region of an antigen recognized by an antibody or lymphocyte receptor.
- T-dependent antigens require the participation of T helper cells and form immunological memory with all isotypes except IgD.
- T-independent antigens have repeating epitopes, induce predominantly IgM, and do not form memory.
- Excessively high doses of antigen can cause immunological tolerance.
- An allergen triggers IgE hyperproduction and mast cell degranulation with the release of histamine.