IMMUNOREGULATION IN HUMAN SCHISTOSOMIASIS

独特型网络相互作用涉及抗原结合位点， 与免疫球蛋白分子的可变区相关。 的 预测是抗原结合抗体和抗- 独特型抗体属于同一家族， 抗原分子或免疫球蛋白可变区。 的 T细胞受体在结合抗原的能力方面也是双重的， MHC II类分子的背景或通过抗克隆型 抗体的 我们的实验室研究了这些独特型/抗独特型T 人类血吸虫病中的细胞相互作用， 意见。 1)从外周血单核细胞中分离的T细胞 感染曼氏血吸虫的患者的细胞能够 在淋巴细胞增殖试验中对抗SEA抗体应答。 2)这种观察到的“抗独特型”反应可以通过以下性质来定义： 抗SEA抗体上表达的独特型。 比如说， 从慢性感染的肠道中收集的抗SEA抗体 患者与恢复的抗SEA抗体具有独特性差异 根据竞争性ELISA数据， 对于每个临床组，用兔抗SEA特异性血清产生。 3)此外，来自慢性肠道患者的抗SEA抗体 能够刺激来自其他组织的外周血单核细胞， 肠道患者以及肝脾患者。 但 急性或肝脾患者的抗SEA抗体， 不能刺激来自任何临床的患者的增殖反应， form. 4)最后，对来自不同年龄组的CD 4+和CD 8 + T细胞群的研究表明， 活动性感染的患者表明，抗SEA抗体可以 刺激这些细胞增殖并调节肉芽肿形成。 这些发现很容易在慢性 肠道病人 肝脾患者无法调节 它们的体外肉芽肿形成表明这些 刺激性独特型来触发调节。 我们的研究集中在 关于精神分裂症患者的特发性描述 以及网络相互作用在调节 宿主/寄生虫反应。 我们现在建议研究独特型/抗- 通过研究人类血吸虫病的基因和 起始抗原/抗体相互作用的蛋白质结构， CD 4+和CD 8 + T细胞上的独特型/TCR或其他配体， 参与肉芽肿的增殖诱导和调节 阵

Idiotypic network interactions involve an antigen-binding site which is associated with the variable region of the immunoglobulin molecule. The prediction is that both the antigen binding antibody and the anti- idiotypic antibody belong to the same family and that each can bind either an antigenic molecule or the immunoglobulin variable region. The T cell receptor is also dual in regard to the ability to bind antigen in the context of MHC Class II molecules or through an anti-clonotypic antibody. Our laboratories have studied these idiotype/anti-idiotype T cell interactions in human schistosomiasis and made the following observations. 1) T cells isolated from peripheral blood mononuclear cells of patients infected with Schistosoma mansoni are capable of responding in a lymphocyte proliferation assay to anti-SEA antibodies. 2) This observed 'anti-idiotypic' response could be defined by the nature of the idiotypes expressed on the anti-SEA antibodies. For example, anti-SEA antibodies collected from chronically infected intestinal patients were idiotypically different than anti-SEA antibodies recovered from hepatosplenic or acute patients based on competitive ELISA data generated with rabbit anti-SEA specific sera for each clinical group. 3) Furthermore, the anti-SEA antibodies from chronic intestinal patients were able to stimulate peripheral blood mononuclear cells from other intestinal patients as well as hepatosplenic patients. However, the anti-SEA antibodies from either acute or hepatosplenic patients were unable to stimulate proliferative responses in patients from any clinical form. 4) Finally, studies on CD4+ and CD8+ T cell populations from actively infected patients demonstrated that anti-SEA antibodies could stimulate these cells to proliferate and regulate granuloma formation. These findings were easily and repeatedly demonstrated in chronic intestinal patients. Hepatosplenic patients were unable to modulate their in vitro granuloma formation suggesting a failure of these stimulatory idiotypes to trigger regulation. Our studies have focussed on the description of the nature of idiotypy in schistosmoiasis patients and the functional role of network interactions in regulation of the host/parasite response. We now propose to study the molecular mechanisms of the idiotype/anti- idiotypic interactions in human schistosomiasis by studying the gene and protein structures of the initiating antigen/antibody interactions and the idiotypic/TCR or other ligands on the CD4+ and CD8+ T cells that are involved in the induction of proliferation and regulation of granuloma formation.