Differentiation, of T cells

Type IV Delayed-type Hypersensitivity (DTH). Delayed-type hypersensitivity reactions are T-cell mediated with no involvement of antibodies. However, these reactions are controlled through accessory cells, suppressor T cells, and monokine-secreting macrophages, which regulate the proliferation and differentiation of T cells. The most frequent form of DTH manifests itself as contact dermatitis. The drug or metabolite binds to a protein in the skin or the Langerhans cell membrane... 

Type IV hypersensitivity responses are elicited by T lymphocytes and are controlled by accessory cells and suppressor T cells. Macrophages are also involved in that they secrete several monokines, which results in proliferation and differentiation of T cells. Thus, there are numerous points along this intricate pathway in which drugs may modulate the final response. To achieve a Type IV response, an initial high-dose exposure or repeated lower-dose exposures are applied to the skin the antigen is carried from the skin by Langerhans cells and presented to cells in the thymus to initiate T-cell proliferation and sensitization. Once sensitized, a second challenge dose will elicit an inflammatory response. Thus, before sensitivity can be assessed, each of the models used to evaluate dermal hypersensitivity requires as a minimum ... 

Interact with antigens increasing the concentration of calcium in cells which in turn induces transcription of the interleukin that stimulates growth and differentiation of T-cells. Interleukin is a hormone of the immune system that is important in the body s response to microbial infections. 

A particularly potent immunosuppressive chemical is TCDD, dioxin. This inhibits the differentiation of T cells by damaging the epithelial cells in the cortex of the thymus. These cells are involved in the maturation of T cells. A receptor is involved with this toxic effect, the AHR receptor, to which TCDD binds very strongly. The receptor is expressed in the thymus. Mice, which to do not express this receptor, do not show this particular toxic effect of TCDD even at 10 times higher doses. 

Also, it interferes with a chain of events, which initiates the immune response. This involves interaction of T-helper cells with the antigen-presenting cells (APCs), which causes activation, proliferation, and differentiation of T cells. A chain of events, which is necessary for this, includes receptor interactions and interaction with cytokines and intracellular transduction molecules. 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity direcdy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-cells, B-cells, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modality for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disseminated intravascular coagulation in mice administered TNF-a and IFN-y. 

Interleukin-2 (IL-2) is an endogenous cytokine that normally exerts a number of beneficial immunologic responses. In particular, IL-2 stimulates the growth and differentiation of T-cell lymphocytes that are selectively toxic for tumor cells.11,33 Hence, recombinant DNA techniques are now used to synthesize IL-2 so that this agent can be used to treat cancers such as renal cancer and malignant melanoma (see... 

Figure 3.8 CD4 differentiation. The open arrows indicate those stimuli that support and the grey arrows those that inhibit the growth and differentiation of T cell subtypes.

Eosinophil differentiation and proliferation, production of IgM and IgA, increased IL-2 receptors, increased IgA secretion Synthesis of acute-phase proteins by hepatocytes, synergistic with IL-3 on multipotential stem cells, growth and differentiation of T cells, dilferentiation to antibody secretion... 

Diets that are low in protein, zinc, selenium, vitamin Bg, and fat may collectively depress immune function. This type of diet may be associated with either a low-caloric-intake diet or low-fat, low-meat-products diet. Zinc is an essential trace element for many biological functions, including immune functions. Indeed, zinc is required for the biological activity of a thymic hormone, called thymulin in its zinc-bound form, and is important for the maturation and differentiation of T-cells. With advancing age, zinc, thymic functions, and peripheral immune efficiency show a progressive decline. Supplementing zinc in old age restores immune efficiency. 

Development and differentiation of T cells in thymus, spleen, or lymph nodes is assessed by T cell surface markers (see Chapters 2.3 and 3.2). Some T cell surface markers can also be used to examine T cell function. For example, the population of CD4p° /CD62L iow/cD44 s is considered memory T cells, whereas cD4p° 7CD25p T cells are considered regulatory T cells in the periphery. 

In mice, CD8a dendritic cells elicit Thl responses, whereas CD8a -dendritic cells favor Th2 responses. CD8a dendritic cells secrete IL-12 which causes other CD8a -dendritic cells to secrete IFN-y that is essential for Thl induction (66). IFN-y activates the antimicrobial activities of macrophages and, together with IL-12, promotes the differentiation of T cells into killer cells (67). 

RA could regulate activation of T cells, B cells, and DCs differentiation of T cells and B cells and production of immunoglobulin and T cell homing to gut. These immunological functions of RA might contribute to human immunity, including preventing gut infection. 

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