Lymphoid changes

MTX exceeds any other marine toxins known in the mouse lethality (0.13 ig/kg) and is 80 times more potent than commercial saponin (Merck) in hemolytic activity. According to Terao (72), MTX induced severe pathomorphological change in the stomach, heart and lymphoid tissues in mice and rats by i.p. injection of 200... 

Flow cytometry is now commonly used in immunotoxicity studies to assess changes in relative frequency and number of lymphoid and myeloid cells in the spleen, lymph nodes, bone marrow and/or peripheral blood of rodents, and in the peripheral blood of humans. A list of selected cell surface markers useful in immunotoxicity studies is shown in Table 7.3. Notably, the majority of available reagents are specific for murine antigens with human reagent availability a close second. Reagents for rat, primate, and... 

While changes in cell phenotypes have proved useful in some settings to characterize the immunotoxicity of xenobiotics,1 phenotypic analysis alone is often not a sensitive indicator of low dose immunotoxicity for many agents that alter immune function. Xenobiotics that exert selective toxicity on lymphoid and myeloid cells may be discovered through immunophenotypic analysis. However, most agents produce immunotoxicity at doses much lower than those required to produce cytotoxicity or interfere with primary lymphoid organ differentiation. Some of the most potent immunosuppressive chemicals that have been tested, such as cyclosporine A, do not alter immunophenotype at doses that are immunosuppressive. On the other hand, when phenotyping is linked to assessment of functional parameters of the cells, immunotoxic effects are more likely to be identified. 

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. 

Female rats exposed acutely to 100 ppm 1,2-dibromoethane for up to seven exposures (see Section 2.2.1.1) had splenic congestion and hemosiderosis no changes in hematopoietic or lymphoid elements were described (Rowe et al. 1952). 

The presence of interstitial histiomacrophage infiltration of interalveolar walls, pneumonia, acute bronchitis, congestion of vessels, hemorrhages, peribronchial and perivascular lymphoid infiltration, foci of emphysema and dystelectasis were eonsidered in the assessment of morphological changes in the lungs. 

It appears possible to judge whether increases in proliferative activity in the lymphoid tissue is systemic on the ground of assessment of megacaryocytes (change markers of proliferative activity in the lymphoid tissue of experimental animals) dynamics in the spleen. 

Figure 12 shows dynamics of the changes in the quantitative characteristics of spleen megakaryocytes. It is obvious that their dynamics is the same as in perivascular and peribronchial lymphoid infiltration study. Hence, perivascular and peribronchial lymphoid infiltration condition reflects systemic reaction of the lymphoid tissue of mice to the maximum concentration of the virus in the lungs and bacterial flora activation in case of MFPC Grinization application which results in more adequate and concordant immune response in animals from group II. 

The thymus, spleen, and lymphoid tissues aU have immunological function and changes to them can be indicative of adverse effects on the immune system. Indications of immunotoxicity from standard repeated dose toxicity smdies include one or more of the following signs ... 

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