Lysis, cell, complement

IgG or IgM antibodies direct the immune response toward the antigen located on a cell (e.g., a red blood cell or thrombocyte). Macrophages, NK cells, and neutrophils are recruited by the antibodies to the site of the antigen on the cell surface and destroy the cell by phagocytosis or lysis. Additionally, complement activation will damage the cell (Fig. 6.32). The result, for example, where red cells are the targets is hemolytic anemia. 

Another type of reaction that may affect the formed elements in blood is the innocent bystander reaction. With this type of reaction, antigen-antibody complexes formed in blood adhere nonspeciflcally to cells. Complement is then activated, resulting in ceU lysis. 

Complement Fixation. Complement is a component of the immune system capable of binding to an antibody after the antibody has reacted with an antigen. If that antigen is part of a whole cell, complement mediates a series of events which results in the lysis of the cell (11). 

Antibodies can damage parasites directly, induce lysis, activate complement, agglutinate extracellular forms, stimulate antibody-dependent cellular cytotoxicity, and block their entry into their host cells. IgM, IgG, and IgA antibody isotypes are involved in these reactions. The isotype specificity not only depends on in which host compartment the parasite is residing (e.g., respiratory tree, GI tract, GU tract [IgA], bloodstream, lymphoid tissue [IgM, IgG]) but also on the antigens expressed during the different developmental stages and their chronicity. 

In our laboratory (Lefkovits, 1972) a microculture method was developed which made it feasible to culture and assay many small aliquots (10 fxl) of lymphoid cells. The samples of the culture fluid or cells are handled by a replicator (Lefkovits and Kamber, 1972) which can remove samples from 60 wells of a tissue culture tray and release them on an assay plate which contains agar with embedded red cells. Complement-dependent zones of lysis mark the cultures which have produced antibody (Fig. 4). 

The Complement System Comprises About 20 Plasma Proteins Is Involved in Cell Lysis, Inflammation, Other Processes... 

Cytotoxic reactions. The antibody and cell react, with resultant lysis of the cell. It was found that the presence of a third component, called complement, was necessary for this reaction to take place. 

Complement induced immune lysis of cells and liposomes to release markers which are then detected electrochemically has been used to detect antibodies and antigens in a homogeneous format at nanomolar levels 252-256) qqjJj amperometric and potentio-metric electrodes have been employed. Unfortunately, major improvements in sensitivity appear unlikely, and instability of liposomes makes development of stable reagents for commercial systems difficult. 

Muronomab-CD3 (OKT-3) is a murine monoclonal antibody that targets the CD3 receptor. The CD3 receptor is only found on activated T cells and medullary thymocytes.10,11,14 After binding with the CD3 receptor, complement-mediated T cell lysis occurs rapidly. This agent is dosed at 5 mg/day. This dose is given daily for 10 to 14 days. Lower doses have been used successfully in liver transplant recipients.14... 

Deposition of urate crystals in synovial fluid results in an inflammatory process involving chemical mediators that cause vasodilation, increased vascular permeability, complement activation, and chemotactic activity for polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes results in rapid lysis of cells and a discharge of proteolytic enzymes into the cytoplasm. The ensuing inflammatory reaction is associated with intense joint pain, erythema, warmth, and swelling. 

II cytolytic Cell-associated Clonal expansion B cells IgM, IgG generated. Ig binds to cell bound antigen in the presence of complement and/or activated macrophages cell lysis occurs Rh factor incompatability, hemolytic anemeia in reaction to drugs... 

Complement fixation Serum Critical component of humoral immune response leading to lysis of cell membranes, chemotaxis, and phagocytosis... 

Figure 1.14. Complement activation via the classical pathway. The sequential activation of complement following antibody deposition onto a surface is shown. C9 forms a pore in the membrane, eventually leading to cell death by osmotic lysis. See text for details.

Complement A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed components of complement and are designated by the symbols... 

Three TNF antagonists are currently approved for the treatment of RA etaner-cept (ETN), infliximab (INF), and adalimumab. ETN a fusion protein of two identical chains of the recombinant human TNF receptor, p75, fused with the Fc portion of human immunoglobulin (Ig) G1 binds to soluble TNF-a in vivo. INF and adalimumab are both monoclonal antibodies to TNF-a INF is chimeric, and adalimumab is fully humanized. Both bind to soluble TNF-a, preventing TNF-a from binding to its receptors on cell surfaces. INF can also bind transmembrane TNF-a, fix complement, and cause cell lysis. 

Figure 17.23 Killing by antibodies and complement working together. Antibodies form a complex with bacteria. The anti-body-bacterium complex can stimulate phagocytosis by macrophages, directly. The complex also activates complement, which stimulates phagocytosis or causes lysis and hence death of bacteria. Activated complex can also lead to inflammation which attracts other immune cells to the site of infection (see Figure 17.24).

Anti-thymocyte globulin (ATG) is a purified immunoglobulin from horse, rabbit, sheep, or goat serum after immunization with human thymocytes. The administration of anti-thymocyte globulin results in a depletion of T-cells as a result of complement dependent lysis and opsonization by the macrophage-monocyte system. The depletion of CD4 positive cells is long lasting and results in an inversion of the CD4/CD8 ratio. There are hardly... 

IgG receptors on cultured, human lymphocytes.526 Sialidase treatment of lymphocytes from sensitized subjects increased the responsiveness to viral, bacterial, and fungal antigens.527 The same treatment of human, Herpes simplex virus-infected cells was found to enhance the sensitivity of the cells to lysis mediated by antibody and complement.528... 

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