Lymphocytes cytotoxic

Immune Defense. Figure 2 Cytokines involved in the development of adaptive immune responses in secondary lympoid tissues such as the lymph nodes or spleen. Abbreviations B B-lymphocyte, IFN interferon, Ig immunoglobulin, IL interleukin, NK natural killer cell, TE T-effector (cytotoxic) lymphocyte, TH T-helper lymphocyte... 

This is an immunoglobulin fusion protein with the cytotoxic lymphocyte antigen 4 (CTLA-4) receptor. By binding to CD80/86 on APCs it inhibits the CD28 costimulatory signal in lymphocytes. It is speculated that this can result in tolerance but up to now there is only experimental data [3,4]. 

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... 

Ab, B.K., Kiessling, R., Van, E.J.D., Thole, J.E.. Kumararatne, D.S., Pisa, P., Wondimu. A., Ottenhoff, T.H. (1990). Induction of antigen-specific CD4+ HLA-DR restricted cytotoxic lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65 kDa heat shock protein. Eur. J. Immunol. 20, 369-377. 

Cho, H.J. et al., Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by aT-helpcr cel I-independent mechanism, Nat. Biotechnol, 18, 509, 2000. 

Third T uptake by resident macrophages 1 uptake by macrophage 1 T insertion of MAC into bacterial membrane 1 T activation of cytotoxic lymphocytes by MHC-viral peptide... 

When a cell is infected with a virus, the latter utilises the metabolic machinery within the host cell to generate viral proteins, RNA and DNA to produce more virus particles which then escape to infect other cells. The process is stopped by death of the host cells so that generation of new viruses is halted. The major mechanism that results in death of the host cell is apoptosis. The cells that are responsible for the death of the infected cells are either cytotoxic lymphocytes or natural killer cells. Death is caused either by release of toxic biochemicals and/or proteolytic enzymes or by binding to a death receptor, which is present on many cells. The entry of proteolytic enzymes or binding to the death receptor results in activation of initiator caspases. These activate effector caspases that cause damage to the cell which results in death due to apoptosis (Chapter 17 Figures 17.28, 29 and 30). 

Several proteins that stimulate subsets of lymphocytes involved in various aspects of the immune response are now produced by recombinant DNA techniques. The pharmacology of these lymphokines as potential anticancer agents is being investigated. Interleukin (IL) 2, originally described as a T-cell growth factor, induces the production of cytotoxic lymphocytes (lymphokine-activated killer cells, or LAK cells). IL-2 produces remissions in 10 to 20% of patients with melanoma or renal cell carcinoma when infused at high doses either alone or with lymphocytes that were previously harvested from the patient and incubated with IL-2 in vitro. 

TFI, TFIj, and cytotoxic lymphocytes (C Ls), regulatory or effector cells. 

AIDS represents the classic example of immunodeficiency disease caused by extrinsic factors, in this instance the human immunodeficiency virus (HIV). This virus exhibits a strong tropism for CD4 T helper cells these become depleted, giving rise to increased frequency of opportunistic infections and malignancies in infected individuals. AIDS is also characterized by an imbalance in THl and TH2 cells, and the ratios of cells and their functions are skewed toward TH2. This results in hypergammaglobulinemia, loss of cytotoxic lymphocyte activity, and delayed hypersensitivity. 

Shalaby, M.R., Shepard, H.M., Presta, L., et al. (1992). Development of humanized bispecific antibodies reactive with cytotoxic lymphocytes and tumor cells over expressing the HER2 proto-oncogene. J. Exp. Med., 175, 217-225. 

Stimulation of Fas and TNF-1 receptors directly activates caspases 2 and 8, but Fas ligands can also activate Bid and so cause the mitochondria to enter the apoptotic process. T lymphocytes (cytotoxic lymphocytes) express the Fas ligand and so can cause activation of the Fas-caspase system in target cells. 

Figure 7.78 Postulated mechanism of halothane immune-mediated hepatotoxicity. This figure is only a partial explanation, involving Tc cells (cytotoxic lymphocytes). See text for complete description. CYP2E1 in liver cell activates the halothane to a reactive acyl chloride shown), which reacts with proteins (e.g., enzymes in the SER). These are transported to cell surface and presented to immune system by APC. Abbreviations APC, antigen-presenting cell SER, smooth endoplasmic reticulum MHCII, major histocompatability complex.

There are three different kinds of lymphocytes that have specific functions T cells, B cells and NK cells. T cells develop in the thymus while B cells develop in the adult bone marrow. The thymus and the bone marrow are the primary lymphoid organs where lymphocytes acquire specific cell surface receptors that give them the ability to recognize antigens. NK cells are cytotoxic lymphocytes that develop in the bone marrow. The phagocytes are made up of either monocytes (macrophages) or polymorphonuclear granulocytes, which include neutrophils, eosinophils and basophils. 

C21. Chiang, A. K., Chan, A. C., Srivastava, G., and Ho, F. C., Nasal T/natural killer (NK)-cell lymphomas are derived from Epstein-Barr virus-infected cytotoxic lymphocytes of both NK-and T-cell lineage. Int. J. Cancer 73, 332-338 (1997). 

Til mors often "iriehed in hyalunsnaiL Cancer cells produce high levels of hyaluronan or stimulate other cells to produce the polysaccharide. This hyaltmman halo protects the cell from cytotoxic lymphocytes [2], Other inves-... 

Vitamin A (retinol) improves the humoral and cellular tolerance of a person who suffers from an infection. By affecting the differentiation of cells and regulating the metabolism of steroids, vitamin A stimulates the activity of macrophages and T-cytotoxic lymphocytes. It also raises secretion of cytokines and production of antibodies (Hughes 1999, Pfahl and Chytil 1996). 

Autoimmune diseases are initiated by activation of antigen-specific T-ceUs. Th2-cells activate B-cells to make autoantibodies, which (by activating complement) damage tissues directly or initiate prolonged inflammation. Cytotoxic lymphocytes and macrophages activated by Thl-cells are directly cytotoxic and also promote inflammation. The events that initiate specific autoimmune diseases are not known, but include ... 

Lang, P., Gesbert, F., Delespine-Carmagnat, M., Stancou, R., Pouchelet, M., and Bertoglio, J. (1996). Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J 15 510-519. 

A more systematic study was performed on the immunomodulatory activity of new alkaloid glycosides. A large range of the glycosides, e.g., of elymoclavine and 9,10-dihydrolysergol, was tested for their stimulatory activity on cytotoxic lymphocytes. These lymphocytes form the effector arm of cell-mediated immune responses to infection and tumors. 

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