Immunosuppressants immunoglobulins

Immunosuppression—anatomic or functional asplenia, sickle cell disease, alcoholism, cirrhosis, immunoglobulin or complement deficiency cancer, HIV/AIDS, debilitated state of health... 

The various organs of the immune system such as spleen, lymph nodes, thymus and bone marrow containing the cells involved in the various immune responses offer the possibility to harvest these cells and perform in vitro assays for evaluation of effects on the immune system. When part of an in vivo animal study this may indicate a direct toxic effect of pharmaceuticals, that is, immunosuppression (Table 18.2). So, it is feasible to obtain cell suspensions for further evaluation such as determination of cellular subsets of T and B leukocytes by fluorescent activated cell sorter analysis (FACS analysis), and determination of natural killer (NK) cell activity of the spleen cell population. An advantage of this approach is that it may lead to identification of a biomarker to be used in clinical studies. In addition, in vitro stimulation of spleen cells with mitogens activating specific subsets may indicate potential effects on the functionality of splenic cell populations. Concanavalin A (Con A) and phytohemagglutinin (PHA) activate Tcells, while lipopolysaccharide (LPS) activates primarily B cell populations. Blood is collected for total white blood cell (WBC) determination and blood cell differential count. In addition, serum can be obtained for determination of serum immunoglobulins. 

Immunoglobulin. Immunoprotein glycoprotein of animal origin with known antibody activity, or protein related by chemical structure, which may or may not have antibody activity. Divided into five classes IgM, IgG, IgA, IgD, and IgE on the basis of structure and biological activity. Immunostimulant. Stimulating various functions or activities of the immune system. Immunosuppressant. An agent capable of suppressing immune responses. 

A. General description Muromonab-CD3 is a murine monoclonal antibody (MW 150 kDa) to the CD3 antigen of human T cells. It functions as an immunosuppressant. The antibody is a biochemically purified IgG2a immunoglobulin... 

Cholinesterase inhibitors—but not direct-acting acetylcholine receptor agonists—are extremely valuable as therapy for myasthenia. Patients with ocular myasthenia may be treated with cholinesterase inhibitors alone (Figure 7-4B). Patients having more widespread muscle weakness are also treated with immunosuppressant drugs (steroids, cyclosporine, and azathioprine). In some patients, the thymus gland is removed very severely affected patients may benefit from administration of immunoglobulins and from plasmapheresis. 

Benzene is such a chemical that damages the bone marrow, and aplastic anemia results. This has several effects, one of which is a reduction in the lymphocyte as well as red cell population and so pancytopenia and therefore immunosuppression results. This leads to an increased susceptibility to infection and inhibited immunoglobulin production. These effects have been detected in both experimental animals and humans occupationally exposed to benzene. Thus, shoe workers in Turkey and China have been found to suffer aplastic anemia. 

As a worst-case scenario the possibility exists to break natural tolerance to human Fc and lead to the formation of anti-Fc antibodies, in vivo, due to the presentation of such a high local concentration of Fc domain epitopes to various components of the cellular immune system. As a result, the generation and function of endogenous immunoglobulins could be negatively affected by the presence of these circulating antibodies (immunosuppression). 

Supraphysiological doses of 1,25-(OH)2D3 produce immunosuppressive effects by causing depletion of thymocytes and decreased immunoglobulin production in mice [365]. A further study of these effects by 1,25-(OH)2D3 showed that hypercalcaemia, induced by 1,25-(OH)2D3 treatment (20 ng/d for 4 days) markedly decreased thymus weight, thymocyte number, and in particular caused atrophy of immature thymocyte subpopulations which re-... 

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