IMMUNE MECHANISMS OF OCULAR INFLAMMATORY DISEASE

候选人的直接目标是发展科学专长。 在分子免疫学和眼生物化学中的应用 致病自身抗原的定义。这将导致长期的 眼球疾病发病机制的独立研究计划的目标 炎症性疾病。应聘者在临床方面有很强的背景 眼科，对眼部炎症表现出兴趣。过去时 研究生院在基础研究方面的成功是她科学研究的证据 超能力。然而，从研究生院到重新进入大学之间的滞后时间 进入基础研究需要一段时间的科学再培训。 加州大学洛杉矶分校将提供一个出色的科学环境，使 发展当前分子生物学专业知识的候选人 免疫学。该项目与健康相关的特点是，它特别 试图定义驱动某些内源性人类的候选抗原 眼部炎症性疾病，可作为治疗的基础 新的诊断测试和治疗干预。 尽管许多免疫介导性炎症性疾病被认为是 从活化的CD4T细胞，B细胞的活化和克隆性扩增 预计将相继发生。这些选定的B细胞具有相同的 致病T细胞及其抗体的抗原性 提供了一种重要的工具来表征驱动 免疫反应。这项提议的主题是使用新技术 III抗体噬菌体展示克隆分离标记抗体和 常见的一种特殊类型葡萄膜炎的候选抗原 患有溃疡性结肠炎(UC)。第一个目标是确定一个 UC中唯一的标志物抗体pancA与炎症有关 葡萄膜炎。将通过酶联免疫吸附试验和免疫荧光筛查进行检测。 一种独特的UC形式的煎饼的人血清。两者之间的关联性 疾病活动性和自身抗体水平也将被确定。这个 第二个目标是识别与人类5-3反应的葡萄膜抗原。 抗Panca抗原的重组单抗。如果这些抗原 经过鉴定，它们将通过蛋白质生物化学来表征，或者 如果有必要，可以通过分子克隆来实现。抗原的疾病关联性 将通过表征B和T细胞对 抗原。第三个目标是开发一个全面的葡萄膜图书馆 与UC抗体反应反应的抗原。生化和 将对这些抗原进行免疫学表征 遵循前述目的的实验模型。

The immediate goal of the candidate is to develop scientific expertise in molecular immunology and ocular biochemistry as applied to the definition of pathogenic autoantigens. This will lead to the long-term goal of an independent research program on the pathogenesis of ocular inflammatory diseases. The candidate has a strong background in clinical ophthalmology with a demonstrated interest in ocular inflammation. Past graduate school success in basic research is evidence of her scientific abilities. However, the lag time between graduate school and re-entry into basic research demands a period of mentored scientific retraining. UCLA will provide an outstanding scientific environment that will allow the candidate to develop current expertise in molecular biology and immunology. The health-relatedness of the project is that it specifically attempts to define candidate antigens that drive certain endogenous human inflammatory diseases of the eye, which can be used as the basis for novel diagnostic tests and therapeutic interventions. Although many immune-mediated inflammatory diseases are thought to result from activated CD4 T cells, B cell activation and clonal expansion is expected to occur in tandem. These selected B cells have the same antigenic specificity of the pathogenic T cell, and their antibodies offer an important tool to characterize the target antigen driving the immune response. The subject of this proposal is to use new techniques iii antibody phage display cloning to isolate marker antibodies and candidate antigens for a distinctive type of uveitis that commonly occurs with ulcerative colitis (UC). The first aim is to determine whether a unique marker antibody in UC, pANCA, is associated with inflammatory uveitis. This will be tested by ELISA and immunofluorescence screening of human sera for the distinct UC form of pANCA. The correlation between disease activity and level of autoantibody will also be determined. The second aim is to identify uveal antigens that react with 5-3, a human recombinant monoclonal antibody to the pANCA antigen. If such antigens are identified, they will be characterized by protein biochemistry, or if necessary, by molecular cloning. Disease association of the antigen will be tested by characterizing the B and T cell responses to the antigen. The third aim is to develop a comprehensive library of uveal antigens reactive with the UC antibody response. Biochemical and immunologic characterization of these antigens will be performed following the experimental model of the preceding aim.