IMMUNOLOGY TEXTBOOK - Mercury Podillia 2013

MECHANISMS OF IMMUNE DEFENSE IN BACTERIAL, VIRAL, FUNGAL, AND PROTOZOAN INFECTIONS

Features of immunity in bacterial infections with a primary chronic course

The second mechanism of Cell-mediated Immune Response is chronic inflammation. It develops in response to pathogens localized within cellular vacuoles (certain Bacteria, mycobacteria causing tuberculosis and leprosy, and some Protozoa such as Leishmania). Antigen presentation is performed primarily by macrophages in association with Class II MHC. Antigen Processing occurs similarly to the HUMORAL IMMUNE RESPONSE—within the vesicular fraction. Activated antigen-presenting CD4 T lymphocytes (T_M) differentiate into type 1 T helper Cells mediated by IL-2. T_M differentiation in this specific direction is driven by IL-2 produced by activated macrophages and IFN produced by natural killer cells activated during the early phase of the response to intracellular parasitic pathogens. As a result, a clone of specific T_M is generated, which activates the mononuclear phagocyte system. Macrophages receive two activation signals from T_M: IFN is secreted by T_M and acts via a specific receptor, while the second signal is provided by the membrane-bound or secreted form of TNF. Although all macrophages express receptors for IFN-γ, those infected macrophages bearing TcR on their membrane that recognize the antigen will be preferentially activated upon contact with T_M.

Thus, the effector mechanism in this type of immune response involves the accumulation of macrophages recruited to the lesion site. Furthermore, some of these cells may fuse together to form a giant multinucleated syncytial Structure, thereby combining the metabolic machinery of the macrophages and enhancing The production of reactive oxygen species and lysosomal Enzymes. If this still fails to eliminate the pathogen, an alternative neutralization mechanism is employed: isolation. Fibroblasts form a fibrous capsule (granuloma), which may become impregnated with calcium salts. The granuloma is a hallmark of chronic inflammation during persistent infection. Any form of immune response begins with the recognition of a foreign antigen—that is, its binding to a specific receptor on the membrane of a mature lymphocyte. Such specific receptors pre-exist on lymphocytes prior to encounter with the antigen. Their immense diversity is ensured by a broad repertoire of lymphocyte clones and the capacity to recognize any foreign antigen. Specific recognition and binding of the antigen to the antigen-recognition receptor triggers lymphocyte activation, manifested by its enhanced proliferation (clonal expansion)—namely, the accumulation of a clone of antigen-specific lymphocytes—followed by lymphocyte differentiation resulting in the acquisition of effector Functions. The outcome of the effector phase of the immune response is the elimination of the antigen mediated by activated lymphocytes, their products, as well as other cells and non-specific defense mechanisms recruited by lymphocytes into the immune response, such as phagocytic cells, natural killer cells, and The Complement System.

Thus, as the process becomes chronic, a predominant suppression of functional immune status parameters is observed (including neutrophil engulfment activity—phagocytic number, phagocytic index, NBT test—along with an elevated level of classes G and D IMMUNOGLOBULINS).