Antigens: definition and basic concepts
Antigen is a high-molecular-weight compound carrying signs of genetically foreign information, which upon entering the body is recognized by the immune system and is capable of triggering an immune response aimed at its elimination. Simply put, an antigen is a foreign molecule in response to which the immune system is activated and antibodies are produced.
Recognition of an antigen by an antibody occurs not along the entire molecule, but via a small region of it. This region is called the epitope (antigenic determinant). The corresponding region of the antibody is the paratope. Epitope and paratope fit each other geometrically like a lock and key. During B-cell maturation, gene rearrangement and selection of paratopes with varying geometry occur, which ensures an enormous diversity of antibodies.
Antigen presentation to the immune system is carried out by only three types of cells — antigen-presenting cells (APCs): macrophages, dendritic cells, and a subset of B cells. APCs link innate and adaptive immunity.
Properties of antigens
There are four main properties of antigens: antigenicity, foreignness, immunogenicity, and specificity.
- Antigenicity is the potential ability of a molecule to induce the synthesis of specific antibodies and interact with immune factors. It is realized through epitopes. Examples: capsular (K), flagellar (H), and somatic (O) antigens of bacteria.
- Foreignness is a mandatory condition for the realization of antigenicity. Antibodies must be produced only against foreign molecules. If the immune response is directed against self-antigens, an autoimmune disease develops. Foreignness is relative: antibodies recognize geometry, not genetics, so cross-reactivity is possible.
- Immunogenicity is the ability of an antigen to elicit a protective reaction of a certain intensity. It depends on the molecular characteristics of the antigen (nature, chemical composition, molecular weight, structure), clearance (dynamics of influx and elimination), and the reactivity of the macroorganism (hereditary features).
- Specificity is the ability to induce an immune response strictly to a specific epitope, which ensures recognition accuracy.
Classification of antigens
According to the degree of foreignness, the following are distinguished:
- Autogenic — the organism's own antigens, normally tolerated;
- Isogenic — antigens of genetically identical individuals (identical twins);
- Syngeneic — antigens of individuals of the same species that are genetically non-identical;
- Allogeneic — from representatives of the same species during transplantation;
- Xenogeneic — donor and recipient belong to different species;
- Cross-reactive — antigens of different organisms that interact with the same immune factors (example: Streptococcus pyogenes and heart tissue).
According to specificity, group-specific (common to a genus or family), species-specific, and variant- (type-) specific antigens of individual strains are distinguished.
According to the degree of immunogenicity, there are: immunogens (complete antigens) — elicit a full-fledged response; haptens (incomplete antigens) — induce a response only in a complex with a carrier protein; tolerogens — induce immunological tolerance; autoantigens. According to conformation, epitopes are divided into linear (continuous) and conformational; according to location, into terminal and central.
Antibodies: origin and functions
Antibodies are key humoral factors of adaptive immunity that circulate in the blood and recognize a wide range of antigens with high specificity. Antibodies are produced by plasma cells — terminally differentiated activated B lymphocytes.
On the surface of a B lymphocyte, antibodies act as a receptor — the BCR (B-cell receptor). After the antigen binds to the BCR, the cell is activated, turns into a plasma cell, and begins to secrete antibodies of the same specificity as its membrane receptor. Under the influence of signals from T helper cells, class switching and affinity maturation occur.
Main functions of antibodies:
- Opsonization — facilitation of phagocytosis through the recognition and retention of the microbe by the phagocyte;
- Neutralization of toxins, bacteria, and viruses, preventing their penetration into cells;
- Activation of the complement system via the classical pathway;
- Participation in antibody-dependent cell-mediated cytotoxicity (ADCC) involving NK cells.
Properties of antibodies: affinity and avidity
Affinity is the degree of specific affinity of the active center of the antibody for the antigenic determinant, that is, the accuracy of the geometric match between the paratope and the epitope. IgG has high affinity, while IgM has low affinity.
Avidity is the total binding strength of an antibody molecule to an antigen, depending on the number of active centers. IgG has two binding sites — lower avidity; IgM as a pentamer has ten sites — higher avidity. Thus, IgG has high affinity with low avidity, whereas IgM has the opposite.
Structure and classes of immunoglobulins
An antibody molecule consists of two heavy (H) and two light (L) chains connected by disulfide bonds. The following are distinguished:
- Fab fragment — the variable part formed by the N-terminal regions of the heavy and light chains; contains the antigen-binding center;
- Fc fragment — the constant part responsible for effector functions: binding to cell receptors, complement activation;
- Hinge region at the junction of Fab and Fc, providing mobility and adaptation to the antigen.
The diversity of antigen-binding sites is achieved through gene rearrangements and somatic hypermutations. Antibodies recognizing self-antigens are eliminated.
According to the structure of the Fc fragment, five isotypes (classes) of immunoglobulins are distinguished:
- IgG, IgD, IgE — monomers;
- IgA — exists as a serum monomer and a secretory dimer;
- IgM — a pentamer with 10 antigen-binding sites, primary response.
Key points
- An antigen is a foreign high-molecular-weight structure; it is recognized by its epitope, and the antibody by its paratope.
- Antigen-presenting cells are exclusively macrophages, dendritic cells, and a subset of B cells.
- Four properties of an antigen: antigenicity, foreignness, immunogenicity, specificity.
- Immunogenicity depends on the properties of the antigen, its clearance, and the reactivity of the organism; complete antigens, haptens, tolerogens, and autoantigens are distinguished.
- Antibodies are produced by plasma cells — activated B lymphocytes; the BCR determines the specificity of the secreted immunoglobulins.
- Affinity is the accuracy of the paratope-epitope match; avidity is the total binding strength due to the number of sites.
- An Ig molecule consists of Fab (antigen-binding) and Fc (effector) fragments connected by a hinge region.
- There are five isotypes: IgG, IgM (pentamer), IgA (mono- and dimer), IgD, IgE.