Cytolytic reactions

The early reports of hepatotoxicity with iproniazid led to the synthesis of non-hydrazine inhibitors, and a report from 19 French drug surveillance centers (26) has reaffirmed the frequency and severity of this adverse effect. There were 91 cases of hepatitis due to all antidepressants (11 with iproniazid) over 5 years. Cytolytic reactions occurred in 11 patients treated with iproniazid 5 died. There was a high titer of antimitochondrial antibodies (M6) in five patients. 

Type II, or cytolytic, reactions are mediated by both IgG and IgM antibodies and usually are attributed to their ability to activate the complement systerrr The major target tissues for cytolytic reactions are the cells in the circulatory system. Examples of type II allergic responses include penicillin-inhemolytic anemia, methyldopa-indMced autoimmune hemolytic anemia, quinidine-induced thrombocytopenic purpura, and sulfonamide-induced granulocytopenia. These autoimmune reactions to drugs usually subside within several months after removal of the offending agent. 

Unlike K-cells, NK-cells participate in cytolytic reactions against tumors without the necessity of prior exposure to tumor antigens (Baldwin, 1977), It has been suggested that these cells may play the major role for the control of tumor growth vitro. 

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... 

Abbreviations used APC, antigen presenting cell CTL, cytolytic T lymphiKyte GvHD, graft versus host disease MLR, mixed leukocyte reaction NMA, NV -monomethyl-L-arginine, N=0, nitric oxide... 

In one case of tubulointerstitial nephritis and nephrotic syndrome induced by Triazolam, a sleep inducer numerous eosinophils [85] were found to infiltrate glomeruli and interstitium suggesting that eosinophils may be pathogenic in this situation. An association with tubulointerstitial nephritis and nephrotic syndrome has also been occasionally reported for penicillin/ amoxicillin induced nephropathies [86]. Several reports have analyzed T-cells in penicillin-induced allergy. CD4 T-cells specific for penicillin may be derived from the patients and produce mainly lL-5, some of them being perforin positive with a cytolytic potential [87]. 2) P-lactam specific clones may be obtained only from patients with adverse reactions the clones were Th2 whatever the type of clinical manifestations and... 

Vlasveld [50] obtained biopsy material from a patient with renal cell cancer who developed acute renal failure in the sixth week of a continuous rIL-2 infusion. The pathology was that of acute tubulo-intersti-tial nephritis. Further studies on cryopreserved peripheral blcxxi lymphocytes revealed specific cytolytic activity against an autologous renal cell line cultured from the biopsy specimen. These findings are consistent with an allergic reaction to IL-2. 

Neutrophils are certainly one of the effector arms involved in destruction of the second inoculum after the establishment of an antitumor immune memory [54, 65, 80]. The cytokines released by engineered tumor cells play a leading role in skewing the memory reaction toward Thl or Th2 [50]. However, secondary rejection is not simply the work of T cells since the selective removal of granulocytes impairs or even abolishes rejection after establishment of either a Thl- or a Th2-deflected immune memory [50]. It may well be that the cytolytic activity of PMN is guided by factors secreted by T cells. 

The First Encounter with NK Cells. The NCI project site visitors arbitrarily transferred the healthy control investigator s (JGS) research funds from M.D. Anderson Hospital to the NCI intramural Herberman laboratory for the clarification of the in vitro artifact reactions . In the clarification efforts, the Herberman laboratory used the modem and accurate radioactivity-release assay , instead of the out-moded and clumsy chamber-slide assay. However the radioactivity-release assay did not distinguish between different types of cytolytic lymphocytes. Neither the HeUstrom, nor... 

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