| Aplastic anemia(AA) is characterized by a failure of blood cell production resulting in varying degrees of pancytopenia with a markedly hypocellular bone marrow. AA was first recognized by Ehrlich in 1888. The name of aplastic anemia was subsequently applied to this disease by Chauffard in 1904 and most cases of AA are acquired. Despite the exact causes of AA are unknow, it has been postulated that there is a genetic predisposition. The disease may result from the accumulated effects of multiple noxious exposures of plurpotential stem cells. Ultimately, all stem cells sustain sufficient damage to hinder their ability to replicate. Alternatively, such expposures may induce a single abnormal cell to proliferate in a clonal fashion and to somehow hinder the growth of normal stem cells. The result would be aplastic anemia. Potential mechanisms responsible for acquired AA include induced defects in hematopoietic stem cells, failure of the bone marrow microenvironment which impaired production or release of hematopoietic growth factors, and cellular or humoral immune suppresion of the marrow. A stem cell defect has been considered for a long time to be the major pathogenetic mechanism resulting in bone marrow failure in the patients with acquired AA. Although it is not possible to assess human totipotenital stem cells in culture, their progeny are easily identified by colony formation in vitro. granulocyte-macrophage colony-forming units(CFU-GM) and burst forming units-erythroid (BFU-E) are reduced markedly in patients with XI I Studies on immunological mechanisms of pathogenesis of aplastic anemia Abstract AA. Further studies showed that reduced colony growth appears to be due to a lymphocyte or T cell suppressor mechanism rather than a reduction or qualitative abnormality in marrow progenitor cells. However, it is unclear whether this is inciting event or represents epiphenomema secondary to the disease. Pathogenetic studies have been conducted of the residual marrow damage in mice that receive busulfan or high dose irradiation to a limb. Although the animals retain relatively normal blood or bone marrow counts at the first situation. When treated with chloramphenicol, animals exposed to busulfan have a marked decrease in progenitor cells whereas controls are unaffected. In the second situation, with high dose of 2OGy irradiation, aplasia marrow appeared and recovered; However, permanent aplasia develops in this limb several months later. This appears to result from late damage to the marrow hematopoietic microenvironment. Based on those studies, a theory of 憇eed (stem cells)?versus 憇oil (microenvironment)?abnormality was established. Co-stimulatory signal, a new model for the activation of T cells, was first proposed by Bretscher PA and have made great contribation to not only in basic research and theory of immunology, but also in its clinical practice. The activation of naive T cells requires the generation of two signals. It postulates that T cells activation requires a first step involving presentation by professional antigen presenting cell (APC) such as dendritic cells, and a second step in which Ag-specific, resting B cells take up the antigen, process it, and subsequently present the peptides of the antigen on their class II MIHC molecules. Inducible co-stimulatory...
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