Immune effectors cytokines

Most transformed cells do not express class II MHC molecules and express lower than normal levels of class I MHC molecules. This renders their detection by immune effector cells more difficult. Treatment with cytokines, such as IFN-y, can induce increased class I MHC expression, which normally promotes increased tumour cell susceptibility to immune destruction. 

Scallon, BJ. et al., Chimericanti- TNF-a monoclonal antibody cA2 binds recombinant transmembrane TNF-a and activates immune effector functions, Cytokine, 7, 251,1995. 

IL-12-stimulated IFN-y production and NK cell activation further potentates the overall immune response, not only to infectious agents but also against transformed cells. Cytotoxic T cells and NK cells represent two of the most important immune effector functions against cancer. IL-12-mediated immunological activity also renders this cytokine a potentially... 

Cytokines and chemokines made by cells such as keratinocytes, macrophages and LC might be expected to recruit and activate leukocytes, which have the potential to kill schistosomula before the development of any adaptive immunity. In vitro, schistosomula have been shown to be susceptible to a wide array of immune effector mechanisms mediated by eosinophils and neutrophils (Butterworth, 1984 Capron and Capron,... 

In recent years it has become clear that the nature of the immune response initiated by CD4 T lymphocytes is at least partly dependent on the selection or preferential activation of particular subsets of CD4 T lymphocytes which secrete defined patterns of cytokines (Table 2.3). These patterns of cytokine release result in the initiation and propagation of distinct immune effector mechanisms. Initial studies of mouse CD4 T lymphocyte clones revealed that these could be divided into two basic fiinaional subsets termed ThI and Th2. ThI T lymphocytes were characterized by the predominant secretion of IL-2, interferon y (IFNy) and tumour necrosis factor 8 (TNF/3), while Th2 cells characteristically... 

The pathogenesis of pulmonary fibrosis is presumably related to initial loss of alveolar type I epithelial cells and endothelial cells. However, the dysregulated repair of pulmonary fibrosis is followed by persistence of inflammation. This is followed by proliferation of type II cells, recruitment and proliferation of endothelial cells and fibroblasts, and deposition of extracellular matrix leading to end-stage alveolar and interstitial fibrosis. These events involve the complex and dynamic interplay between diverse immune effector cells and cellular constituents of the alveolar-capillary membrane and interstitium of the lung. Interaction of these diverse cell populations and the cytokines that they produce culminate in chronic inflammation, angiogenesis, fibroproliferation, and deposition of extracellular matrix. 

As already described in Sects. 15.2 and 15.3, immunotherapy is heavily hampered by the morphologically aberrant tumor microvasculature and increased interstitial fluid pressure, which can impede the delivery of cytokines and monoclonal antibodies and can prevent immigration of immune effector cells into the established tumor parenchyma. 

Female Fischer 344 rat offspring, 13 weeks old dams bred at 9 weeks Pregnant dams exposed to 0, 100, 250, 500 ppm Pb (acetate) beginning 9 weeks old offspring Pb-exposed only in utero Pb modulated immune, macrophage cytokine and effector functions TNF-o, NO production elevated at 250 ppm decreased DTH reactions in 250 ppm group and IFN in the 500 ppm group Miller et al. (1998)... 

Scallon BJ, Moore MA, Trinh H, et al. Chimeric anti-TNF-alpha monoclonal antibody cA2 hinds recombinant transmemhrane TNF-alpha and activates immune effector functions. Cytokine 1995 7 251-259. 

One of the rationales for the use of cytokine gene therapy in mesothelioma is that exogenous cytokines are known to have direct antiproliferative effects upon mesothelioma cells, as well as the ability to activate intrapleural and intratumoral immune effector cells in vivo. Several published Phase I and Phase II clinical trials have decumenfed mesothelioma tumor responses to intrapleural infusion of interleukin-2 (IL-2), interferon-P (IFN-P), and inteiferon-y (IFN-y) (70-76). In particular,... 

Parallel to orchestrating acute inflammatory processes by providing an optimal milieu of cytokines, mediators, and adhesion molecules in order to recruit and activate effector cells to the site of infection, dendritic cells also setve as professional antigen-presenting cells for cells of the adaptive immune system ( antigen presentation ... 

In the specialized environment of secondary lymphoid tissues such as lymph nodes or spleen, dendritic cells provide the requirements for naive T-lymphocytes to become activated and to proliferate. The professional antigen-presenting cells present peptides in MHC II, express costimulatory molecules, and release cytokines into the immunological synapse, which is formed by the antigen-presenting cell and the naive T-lymphocyte. Thus, cells of innate immunity initiate and facilitate the activation of naive lymphocytes, and it is easily conceivable that their cytokines and adhesion molecules will instruct the naive T-lymphocyte during activation and differentiation to T-effector cells. 

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... 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Immunomodulators are a group of mostly stimulatory effectors which act on cells of the immune system (e.g. cytokines, interferons). 

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