IMMUNOREGULATION IN HUMAN SCHISTOSOMIASIS

独特型网络相互作用涉及一个抗原结合位点，该位点 与免疫球蛋白分子的可变区相关。这个 预测抗原结合抗体和抗-HBs 独特型抗体属于同一家族，每个抗体都可以结合 抗原分子或免疫球蛋白可变区。这个 在结合抗原的能力方面，T细胞受体也是双重的 MHC II类分子的背景或通过抗克隆型 抗体。我们的实验室已经研究了这些独特型/抗独特型T 血吸虫病患者细胞间相互作用的研究进展 观察。1)从外周血单核细胞中分离T细胞 感染曼氏血吸虫患者的细胞能够 在淋巴细胞增殖试验中对抗SEA抗体的反应。 2)这种观察到的‘反独特型’反应可以由自然定义 在抗SEA抗体上表达的独特型。例如, 从慢性感染肠道中收集抗SEA抗体 患者独特型不同于抗SEA抗体的恢复 来自肝脾或急性患者的竞争性酶联免疫吸附试验数据 各临床组用兔抗SEA特异性血清生成。 3)慢性肠病患者血清中抗SEA抗体的检测 能够从其他来源刺激外周血单核细胞 肠道患者以及肝脾患者。然而， 来自急性或肝脾患者的抗SEA抗体 无法从任何临床刺激患者的增殖性反应 形式。4)中国人外周血中CD4+和CD8+T细胞亚群的研究 活动性感染的患者证明抗SEA抗体可以 刺激这些细胞增殖并调节肉芽肿的形成。 这些发现很容易并反复地在慢性疾病中得到证实 肠道病人。肝脾患者不能调节 它们在体外形成的肉芽肿表明这些 刺激性白痴触发监管。我们的研究集中在 关于血吸虫病患者独特型性质的描述 以及网络相互作用在调节细胞周期中的功能作用 宿主/寄生虫反应。 我们现在建议研究独特型/抗病毒的分子机制。 人类血吸虫病独特型相互作用的研究 启动抗原/抗体相互作用的蛋白质结构和 CD4+和CD8+T细胞上的独特型/TCR或其他配体 参与肉芽肿的诱导增殖和调节 队形。

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.