IMMUNOPATHOLOGIC STUDIES OF HEYMANN NEPHRITIS

大多数形式的肾小球肾炎是由免疫复合体介导的 受伤。免疫复合体在肾小球中的沉积已被证明是 循环免疫的原位形成和捕获的结果 复合体。这项建议的目的是调查 肾小球免疫复合体形成的另一种机制。 提示在Heymann大鼠的膜性肾病模型中， 循环抗原通过内部图像与肾小球抗原结合。 用循环抗原免疫可产生初级 抗体和抗独特型抗体。反独特型的一个子集 抗体将带有适当的内部图像，将模仿 免疫抗原，因此会与肾小球抗原结合。至 研究这一假说、两种抗原以及原发和抗独特型 抗体将被分离，它们将通过内部图像结合 下定决心。 循环抗原与肾小球抗原结合的证据 随后的抗体沉积可以解释上皮下的定位 膜性肾病中的免疫沉积。此外，制作 模拟抗原的抗独特型抗体已被推测为 有助于自身免疫的发展。确认 Heymann肾炎疑似抗原的内部影像关系 提供了评估这一假设的机会。

Most forms of glomerulonephritis are initiated by immune complex-mediated injury. Immune complex deposition in the glomerulus has been shown to result from both in situ formation and trapping of circulating immune complexes. It is the purpose of this proposal to investigate the role of an additional mechanism of glomerular immune complex formation. It is suggested that in the Heymann rat model of membranous nephropathy, a circulating antigen binds to a glomerular antigen via internal images. Immunization with the circulating antigen results in production of primary antibody and anti-idiotypic antibody. A subset of the anti-idiotypic antibodies will bear the appropriate internal image, will mimic the immunizing antigen, and thus will bind to the glomerular antigen. To investigate this hypothesis, the 2 antigens and primary and anti-idiotypic antibodies will be isolated and their binding via internal images will be determined. Demonstration that a circulating antigen binds to a glomerular antigen with subsequent antibody deposition would explain the subepithelial localization of immune deposits in membranous nephropathy. In addition, the production of anti-idiotypic antibodies that mimic antigen has been postulated to contribute to the development of autoimmunity. Confirmation of the internal image relationships in the putative antigens of Heymann nephritis offers the opportunity to evaluate this postulate.