IMMUNOPATHOLOGIC STUDIES OF HEYMANN NEPHRITIS

大多数形式的肾小球肾炎是由免疫复合物介导的 损伤 肾小球中的免疫复合物沉积已被证明 结果是原位形成和捕获循环免疫 配合物 本提案的目的是研究 肾小球免疫复合物形成的另一种机制。 提示在Heymann大鼠膜性肾病模型中， 循环抗原通过内部图像与肾小球抗原结合。 用循环抗原进行免疫导致产生初级抗原。 抗体和抗独特型抗体。 抗独特型抗体的一个亚类 抗体将带有适当的内部图像，将模仿 免疫抗原，并因此将结合肾小球抗原。 到 研究这一假设，2个抗原和主要和抗独特型 抗体将被分离，并且它们通过内部图像的结合将被 测定 证明循环抗原与肾小球抗原结合， 随后的抗体沉积可以解释上皮下定位 膜性肾病的免疫沉积 另外还生产 模拟抗原的抗独特型抗体被假定为 有助于自身免疫的发展。 确认 Heymann肾炎推定抗原的内部图像关系 提供了评估这个假设的机会。

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.