ACTIVATION OF THE COMPLEMENT SYSTEM

补体系统的激活导致选择性和控制性的免疫应答。 C4和C3分子通过经典的或 经典途径和替代途径。 碎片相互作用 这两种分子的抗原抗体复合物和表面 不同细胞类型上的受体用于调节补体依赖性 功能协调发展的 虽然已经积累了大量的知识， 替代途径，与经典途径相关的相同信息 不太完整。 本申请提出的研究主要针对 描述了相关蛋白质的一些结构和功能方面 在蛋白质的形成和一些结构和功能方面， 参与经典途径C3的形成和功能 转化酶 具体而言，我们计划1）进一步描述主要 C4裂解片段的激活和失活过程中产生的 分子。 将碎片分离至均一性，并进行 化学分析 2)伴随的构象变化分析 通过各种酶促转化和降解失活C4 方法. 这些研究将使用差异表面标记， 允许识别参与的分子的不同区域， 这些功能变化。 3)结构要求调查 对于对照蛋白质C4-bp和I与液相的相互作用， 和表面结合的C4 b。 4)观察到一种异常蛋白质， 病理条件下的人血清，C4肾炎因子， 促使研究在正常血清中鉴定出一种蛋白质， 稳定C4 b2 a酶。 这种蛋白质的鉴定将 完成类比的形成，功能和调节， 经典和替代C3转化酶。 申请的第二部分 上述研究所感兴趣的是， 补体系统通过含有伊加和IgM的免疫复合物。 此外，本发明还提供了一种方法， 通过非免疫机制激活补体的机制 将研究使用光毒性化学品。

Activation of the complement system results in a selective and control fragmentation of the C4 and C3 molecules via the classical, or the classical and alternative pathways respectively. Interaction of fragments of these two molecules with antigen-antibody complexes and with surface receptors on different cell types serve to modulate complement-dependent functions. Although a great deal of knowledge has been accumulated on the alternative pathway, the same information relating to the classical pathway is less complete. This application proposes studies aimed primarily at delineating some structural and functional aspects of the proteins involved in the formation and some structural and functional aspects of the proteins involved in the formation and function of the classical pathway C3 convertase. Specifically, we plan to 1) Further characterize the major cleavage fragments of C4 produced during activation and inactivation of the molecule. The fragments will be isolated to homogeneity and subjected to chemical analysis. 2) Analysis of the conformational changes accompanying the enzymatic conversion and degradative inactivation of C4 by various methods. These studies will use differential surface labeling which will allow the identification of distinct regions of the molecule involved in these functional changes. 3) Investigation of the structural requirements for the interaction of the control proteins, C4-bp and I, with fluid phase and surface bound C4b. 4) The observation of an abnormal protein seen in humans serum under pathological conditions, C4 nephritic factor, has prompted studies to identify a protein in normal serum capable of stabilizing the C4b2a enzyme. The identification of this protein would complete the analogies to the formation, function and regulation of the classical and alternative C3 convertases. A second part of the application to which the above studies are of interest involves the activation of the complement system by IgA and IgM containing immune complexes. In addition, the mechanisms of complement activation by a non-immunologic mechanism using phototoxic chemicals will be investigated.