T and B-cells

The NHR contains also the conserved Calcineurin docking site, PxlxIT, required for the physical interaction of NEAT and Calcineurin. Dephosphorylation of at least 13 serines residues in the NHR induces a conformational change that exposes the nuclear localization sequences (NLS), allowing the nuclear translocation of NEAT. Rephosphorylation of these residues unmasks the nuclear export sequences that direct transport back to the cytoplasm. Engagement of receptors such as the antigen receptors in T and B cells is coupled to phospholipase C activation and subsequent production of inositol triphosphate. Increased levels of inositol triphosphate lead to the initial release of intracellular stores of calcium. This early increase of calcium induces opening of the plasma membrane calcium-released-activated-calcium (CRAC) channels,... 

Idiotypic network. Idiotypic determinants (idiotypes) are unique antigenic epitopes characteristic of the antigen receptors on the surface of T and B cells. They are associated with the variable regions of these receptors. Antibodies produced by B cells as the result of antigenic stimulation can themselves stimulate the production of auto-anti-idiotypic antibodies which have the ability to combine with the B-cell receptor (Ig) and thus can dampen down the immune response. Idiotypes may likewise stimulate the production of T cells specific for idiotypic determinants. Jerne (1974) postulated his... 

Tolerance can also be induced in adults, but higher doses ofthe antigen are required where it has been shown that both T and B cells are made unresponsive. As most antibody responses are T-dependent it is likely that it is these cells which are the ones affected. In order to maintain this state of tolerance it is necessary for the antigen to persist in the animal, as in its absence immunocompetent cells which are being produced throughout life are not being rendered tolerant. 

Solid organ transplant recipients have a blunted immune response to vaccines because the immunosuppressive regimens used to prevent organ rejection inhibit both T- and B-cell proliferation. Many of these patients will also have secondary hypogammaglobulinemia post-transplantation. Prior to transplant, children should complete primary immunization schedules if possible accelerated schedules may be used. Adults should have all vaccinations updated prior to transplantation.16... 

Kim CH, Broxmeyer HE. Chemokines signal lamps for trafficking of T and B cells for development and effector function. J Leukoc Biol 1999 65 6-15. 

Wurbel MA, Malissen M, Guy-Grand D, et al. Mice lacking the CCR9 CC-chemokine receptor show a mild impairment of early T- and B-cell development and a reduction in T-cell receptor gammadelta(+) gut intraepithelial lymphocytes. Blood 2001 98 2626-2632. 

TNF (17.5) Monocyte/macrophage, lymphocyte, neutrophil, endothelium, fibroblast, keratinocyte Activation of T and B cells, natural killer cells, neutrophils, and osteoblasts. Stimulation of endothelial cells to release chemotactic proteins, NO and PGI2. Tumoricidal activity. Induces fever, sleep, hepatic acute phase protein synthesis, catabolism, ACTH release. Lead to myocardial depression, hypotension/shock, hypercoagulability, and death. Stimulates production of IL-1, IL-6, IL-8, IFN-y, and H202. Suppression of cytochrome P-450, thyroglobulin, and lipoprotein lipase. Induces complement activation, release of eicosanoids, including PAF. Procoagulant activity. 

The interleukin-2 receptor (IL-2R) is important in that the cytokine IL-2, secreted by a subset of T-helper cells, enhances the proliferation of activated T and B cells and increases the cytolytic activity of natural killer (NK) cells and the secretion of IgG. 

It has been estimated that 1-2 per cent of the US population suffer from autoimmune conditions, including rheumatoid arthritis, MS and some forms of diabetes. In many instances, an autoimmune response results from the inappropriate activation of a specific subset of B- and/or T-lymphocytes. The most common immunotherapeutic approach to potentially treat such diseases is to induce depletion of the individual s T- and B-cell populations. This could be achieved by administration of an antibody raised against a surface antigen present on such cells. Initial trials, for example, have shown that injection of an (unconjugated) anti-CD4 antibody (cell surface glycoprotein present on many T-lymphocytes) over 7 days significantly reduced the clinical symptoms of rheumatoid arthritis for several months. 

The unique domain following the SH4 domain from the N-terminus is a region with considerable variation in the amino acid sequences among different Src family members. This unique domain may be involved in protein-protein interactions. For example, the unique region of Lck is linked to CD4 and CD8, while those of Fyn and Lyn may be associated with the T- and B-cell antigen receptors. 

Iglesias, A., Bauer, J., Litzenburger, T. etal. T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis. Glia 36 220-234,2001. 

Immunoglobulins (Igs) can activate the complement system, which amplifies the immune response by enhancing chemotaxis, phagocytosis, and release of lymphokines by mononuclear cells that are then presented to T lymphocytes. The processed antigen is recognized by the major histocompatibility complex proteins on the lymphocyte surface, resulting in activation of T and B cells. 

Based upon recent controlled studies, there is considerable evidence that opioids such as morphine induce substantial effects on immune status. For example, it has been shown that morphine administration is associated with alterations in a number of immune parameters, such as natural-killer cell activity [12,13], proliferation of lymphocytes, [13, 14] antibody production [15,16], and the production of interferon [17]. Studies in our laboratory have shown that acute morphine treatment in rats suppresses splenic lymphocyte proliferative responses to both T- and B-cell mitogens, splenic natural-killer cell activity, blood lymphocyte mitogenic responsiveness to T-cell mitogens, and the in vitro production of the cytokines interleukin-2 and interferon-y [18-22], Furthermore, the immune alterations induced by morphine are dose-dependent and antagonized by the opioid-receptor antagonist, naltrexone (e.g., [22]). 

In summary, although numerous AhR-dependent changes in the bone marrow and thymus have been found in TCDD-treated mice, it appears that these effects are self-limiting in adult mice, as T and B cell numbers are not reduced in secondary lymphoid tissue except after exposure to high doses of TCDD or in the context of an adaptive immune response. More subtle effects, such as changes in the antigenic specificity of peripheral T and B lymphocyte populations, have not been documented. 

Lymphocytes, the effector cells of the acquired immune system, include morphologically indistinguishable T and B cells, the former divided into CD4+ T helper cells and CD8+ cytotoxic T cells. Since the functions of those cell subsets differ so drastically, it became important to develop tools to distinguish them from each other. Efforts to identify cell subsets according to their expression of different surface antigens have been successful, including various Cluster of Determination (CD) markers (Table 23.1). In addition, cross-reactive monoclonal antibodies, and subsequently developed species-specific polyclonal and monoclonal antibodies towards the major histocompatibility complex (MHC) have been used to label cells in circulation and in tissue sections (Table 23.1). 

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