Antibody-dependent cytotoxic type

Type II reactions antibody-dependent cytotoxic type. The drug or metabolite combines with a protein in the body so that the body no longer recognises the protein as self, treats it as a foreign protein and forms antibodies (IgG, IgM) that combine with the antigen and activate complement which damages cells, e.g. penicillin- or methyldopa-induced haemolytic anaemia. 

Large granular lymphocytes, not belonging to either the T- or B-cell lineage. Natural killer (NK) cells are considered part of the innate defense system since, in contrast to cytotoxic T-cells, they are able to kill certain tumor cells in vitro without prior sensitization. The basal activity of NIC cells increases dramatically following stimulation with type I IFNs. In addition, NK cells display Fc-receptors for IgG and are important mediators of Antibody-Dependent-Cell-mediated-Cytotoxicity (ADCC). 

The histopathological features of PM may be radically different from those of JDM and ADM. There is little, if any, evidence of involvement of the micro vasculature and the muscle necrosis which occurs appears to be the direct result of targeting of individual muscle fibers. In the dermatomyositis syndromes, antibody-dependent humoral mechanisms are predominant and B-lymphocytes are seen to be the most abundant cell type in almost all JDM cases and a substantial proportion of ADM cases. In contrast, most muscle biopsies from PM patients show evidence of inflammation in which TS (cytotoxic) lymphocytes predominate (Figure 20). Moreover, the distribution of inflammatory cell infiltrates tends to be different. Instead of the mainly perifascicular location of lymphocytes in JDM/ADM, there... 

Shinkawa T, Nakamura K, Yamane N, shoji-Hosaka E, Kanda Y, Sakurada M, Uchida K, Anazawa H, Satoh M, Yamasaki M, Hanai N, Shitara K. The absence of fucose but not the presence of galactose or Bisecting A-Acetylglucosamine of human IgGl complex-type oligosaccharides shows the critical role of enhancing the antibody-dependent cellular cytotoxicity. J Biol Chem 2003 278 3466-3473. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

Type II Drugs often modify host proteins, thereby eliciting antibody responses to the modified protein. These allergic responses involve IgG or IgM in which the antibody becomes fixed to a host cell, which is then subject to complement-dependent lysis or to antibody-dependent cellular cytotoxicity. 

Following recent advances in antibody engineering, it is now possible to s)mthesize humanized antibodies [35]. Because of clinical applicability, antibody-based medicines are one of the biopharmaceutical categories that have attracted close attention in recent years [36]. IgG has been most frequently used for the prevention and treatment of various diseases. The CH2 region of IgG has A-linked carbohydrates (usually complex type double stranded chains) in diverse manners (O Scheme 14). It has recently been revealed that differences in the carbohydrate structure affect the effecter activity of antibodies such as antibody-dependent cellular cytotoxicity (ADCC) and their half-life in blood, inviting close attention from the viewpoint of improving the responses to antibody-based medicines [37,38,39]. 

Some phenothiazines, the so-called half-mustard type, stimulated T-cell blast formation, presented a natural killer cell activity, via possibly the activation of monocytes and macrophages, and an antibody-dependent cellular cytotoxicity of human peripheral blood mononuclear cells, and also showed cytotoxicity against several human cancer cell lines. These phenothiazines also might induce an in vivo antimicrobial activity by possibly their host-mediated immuno-potentiation [146]. Phenothiazines did not demonstrate any apparent mutagenic activity, but they were rather antimutagenic. These data suggest the possible applicability of half-mustard type phenothiazines and benzo[a]phenothiazines to cancer chemotherapy. 

Receptors for the Fc region of IgG are found on a number of cell types and are associated with a variety of functions including phagocytosis (monocytes, macrophages, neutrophils), antibody-dependent cellular cytotoxicity (monocytes, mac-... 

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