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Production of Antibodies
Synthesis and production of antibodies typically is dependent on complex interaction of three cells: (a) macrophages, (b) helper T cells, and (c) B cells.
Antigens are presented to immunocompetent cells by anti-gen presenting cells (APCs), such as macrophages and dendritic cells. Processing by macrophages appears to be a prerequisite for formation of antibodies against many T-cell-dependent antigens, such as proteins and erythrocytes. However, antibody production does not require macrophage participation in case of T-cell-independent antigens. Both the macrophages and dendritic cells present the antigen either native or processed at the cell surface. Macrophages play a key role by modulating the optimum dose of antigen presented to lymphocytes to induce the immune responses.
After processing of antigens by a macrophage, fragments of antigen appear on surfaces of macrophages in association with class II MHC proteins. The antigen-class II MHC protein com-plex binds to specific receptors present on the surface of helper T cells. Subsequently, these helper T cells produce cytokines that activate B cells, producing antibodies that are specific for that antigen. The activated cytokines are interleukin-2 (T-cell growth factor), interleukin-4 (B-cell growth factor), and inter-leukin-5 (B-cell differentiation factor). The activated B cells undergo clonal proliferation and differentiate to form plasma cells, which then produce specific immunoglobulins (antibod-ies). Major host defense functions of antibodies include neu-tralization of toxins and viruses and opsonization (coating) of the pathogen, which aids its uptake by phagocytic cells.
Although helper T cells play a key role in the formation of antibodies, certain substances (e.g., polysaccharides) can acti-vate B cells directly without the help of T cells. Such substances are called T-cell-independent antigens. These antigens, how-ever, induce only the production of IgM antibodies but not other antibodies by B cells. This is because B cells require inter-leukins 4 and 5 to switch classes to produce IgG, IgA, and IgE. These interleukins 4 and 5 are produced by T helper cells only.
B cells perform two important functions: First, they recognize antigens with their surface IgM that acts as an antigen recep-tor; second, they present epitopes to helper T cells in associa-tion with class II MHC proteins. IgM antigen receptor on the B cells recognizes foreign proteins as well as lipids, carbohydrates, DNA, RNA, etc. On the other hand, class II MHC proteins pres-ent protein fragments to the helper T cells. The IgM antigen receptor binds with this wide variety of molecules that stimulate B cells to produce antibodies against all the molecules possible.
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