IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

STRUCTURE AND PRINCIPLES OF FUNCTIONING OF THE IMMUNE SYSTEM

Stages of Immune Response Development

The Immune Response begins with the recognition of a foreign antigen, namely its binding to a specific receptor on the membrane of a mature lymphocyte. Such specific receptors exist on lymphocyte membranes even before exposure to the antigen.

Antigens are defined as substances possessing two key properties: 1) immunogenicity — The ability to induce a specific immune response, resulting in The production of Antibodies or immune lymphocytes; and 2) antigenicity — the ability to specifically react with antibodies or Cells produced in response to the Introduction of that specific antigen. Immunogenic substances are always antigens, whereas antigens are not always capable of acting as immunogens.

Antigens that lack immunogenicity are termed haptens. A hapten on its own is incapable of inducing an immune response, the production of immune lymphocytes, or antibodies, yet it is able to react with them. Furthermore, because a hapten is a low-molecular-weight molecule, its small size prevents it from triggering an immune response; however, upon binding to a larger protein molecule (referred to in this context as a carrier), it acquires immunogenic properties. Such carrier molecules may include albumin, globulins, or synthetic Peptides.

An epitope, or antigenic determinant, is a site on or within an antigen that reacts specifically with an antibody. Thus, the epitope defines the Specificity of the molecule and induces an antibody response. Typically, epitopes are extremely small in size, comprising 4–5 amino acid or monosaccharide residues. Antigens are multivalent, meaning they generally possess A large number of epitopes, each of which stimulates the production of its own specific antibodies within the Organism.

Their vast diversity is ensured by a broad spectrum of lymphocyte clones and the capacity to recognize any foreign antigen. Specific recognition and binding of the antigen to the antigen-recognizing receptor trigger lymphocyte activation, which manifests as enhanced proliferation (clonal expansion)—that is, the accumulation of a clone of antigen-specific lymphocytes—followed by lymphocyte differentiation accompanied by the acquisition of effector Functions. The result of the effector phase of the immune response is the elimination of the antigen mediated by activated lymphocytes, their products, and other cells and mechanisms of nonspecific defense recruited by lymphocytes into the specific immune response, such as phagocytic cells, NK cells, and The Complement System.

The lymphoid system mediates Two Types of specific immune responses: humoral Immunity, involving antibody synthesis, and cellular immunity, encompassing delayed-type hypersensitivity reactions, transplantation immunity, and autoimmune reactions driven by both humoral and cellular immune mechanisms. It is generally believed that the function of humoral immunity is to rid the body primarily of antigenically foreign exogenous substances, whereas cellular immunity eliminates autoantigens, which may include mutated or denatured host cells.

Carrying out humoral immune reactions requires the cooperation of several parallel and sequentially proliferating populations of lymphoid cells that differentiate, recognize, and respond to the antigen, alongside effector cells and accessory cells that facilitate antigen recognition, Processing, clonal proliferation, and differentiation—namely, macrophages, dendritic cells, and helper T cells.

The execution of the immune response takes place within various morphological microstructures of Lymphoid Organs, which provide the conditions for specific spatial interactions between Thymus-dependent and thymus-independent lymphocytes, for antigen phagocytosis and concentration, for antigen contact with cellular elements, and for the proliferation, differentiation, and cooperation of cells involved in the immune response. In Lymph Nodes AND the Spleen, these structural units include marginal sinuses, medullary sinuses and cords, the paracortical zone, lymphoid follicles, germinal centers, arteriolar sheaths of the central Arteries in the white pulp of the spleen, and plasma Cell islets. Characteristic morphological changes occur within these structures upon antigenic stimulation.

Stages of the immune response:

1. Antigen presentation. Antigen-presenting cells include: 1) macrophages, which typically present antigens of bacterial origin derived from the engulfment and intracellular processing of Bacteria; 2) B lymphocytes, which present microbial and toxin antigens bound to their surface immunoglobulin receptors; and 3) dendritic cells, which are the most versatile antigen-presenting cells essential for initiating the primary immune response, including the presentation of tumor antigens.

If the antigen is particulate (such as a microbe or other particle), it is engulfed by macrophages and digested within a phagosome. Small peptides are subsequently re-expressed on the membrane in a complex with MHC Class II and presented to helper T cells (Signal I). Simultaneously, the macrophage becomes activated and releases IL-1 and other cytokines that stimulate helper T cells (Signal II). Bacteria-stimulated macrophages secrete IL-12, which enhances the differentiation of T helper cells into type 1 T helper cells (Th1). If the antigen is presented by B lymphocytes, type 2 T helper cells (Th2) are generated.

2. Inductive phase. Having received two signals from macrophages, type 1 and/or type 2 T helpers secrete an appropriate set of cytokines that stimulate the proliferation of both T Lymphocytes and B lymphocytes. Furthermore, B lymphocytes bearing a monomeric IgM as a receptor specific for that antigen are activated, resulting in the Selection and preferential stimulation of those B lymphocytes.

3. Effector stage. B lymphocytes transform into antibody-secreting plasma cells, the specificity of which increases in the progeny of dividing cells (a phenomenon known as the affinity maturation of B lymphocytes). Concurrently, antigen-specific T effectors emerge, bearing antigen-specific T-cell receptors (TCRs) on their surface. As a result of antigenic stimulation, antibodies and immune T cells (cytotoxic T cells) are generated within the body.

Simultaneously with The Development of the immune response, suppressive mechanisms and suppressor cells are stimulated to inhibit it. Therefore, after a certain period of time, the immune reaction normally subsides. Immunological memory—consisting of memory T AND B cells—persists within the organism.

Upon the initial contact of immunocompetent cells with an antigen, a primary immune response develops. Temporally, the primary immune response proceeds through distinct stages:

Stage I takes 3–4 days; antibodies against the respective antigen are not yet detectable in the serum.

Stage II — 10–14 days post-antigen exposure, IgM and IgG appear in the Blood serum.

Stage III — antibody levels remain constant.

Stage IV spans months and is characterized by a gradual decline in antibody levels.

The secondary immune response develops upon re-exposure to the antigen, accompanied by the production of class G IMMUNOGLOBULINS. Antibodies, predominantly IgG, appear more rapidly and in higher titers than during the primary immune response.