MOLECULAR PARASITOLOGY AND PARASITIC DISEASE

该计划的长期目标是确定钉螺的抗原 与眼部和皮肤病的发展有关的扭转以及与 提高对分子发病机制的认识。盘尾丝虫病就是其中之一 是人类的主要致盲疾病，也是 皮肤病。这种疾病被认为是由免疫介导的，但 大多数症状的确切发病机制尚不清楚。疾病控制方式： 对世界上大多数地区来说，攻击媒介黑蝇是不现实的。 此外，尽管定期给予伊维菌素可能会抑制 疾病，这样的养生方式是医疗保健所不能及的 许多发展中世界的基础设施。因此，改进了 显然，了解疾病的发病机制是必要的。这项建议是 旨在建立一个多学科的互动计划， 利用老牌调查人员的专业知识来应用 人类的分子生物学和分子免疫学技术 盘尾丝虫病。这是基于以现场为基础的临床和 盘尾丝虫病基础免疫学研究进展 在美国和西非生活了11年。项目1将确定个人 眼睛或皮肤病，并提供试剂来定义抗原和 在分子水平上与临床疾病相关的表位和测试 已定义的抗原，作用于疾病患者的细胞。以此为基础 疾病的地理变异和伊维菌素的影响 将检查对免疫反应的治疗。项目2将确定 并鉴定编码疾病相关抗原的克隆，并将 研究森林和稀树草原差异的遗传基础 致病表位。项目3将准备T淋巴细胞克隆以对抗 疾病相关抗原；这些克隆将被用于T表位 最活跃抗原的作图和功能研究。项目4将 检测重组抗原在豚鼠角膜炎模型和 定义致病表位和MHC反应性限制。核心A将 为项目1-4提供蛋白质和多肽化学及表位测绘 专业知识。核心B将提供必要的启动材料 项目1、2、3和4。这个多学科项目的目标是 聚焦这群调查人员所代表的非凡才华 在一个不容易受到更多限制的疾病问题上 方法，目的是为最终控制疾病作出贡献。

The long-term objective of this Program is to define antigens of Onchocerca volvulus that are related to development of ocular and skin disease and to improve our understanding of molecular pathogenesis. Onchocerciasis is one of the leading blinding diseases of humans as well as a leading cause of skin disease. The disease is believed to be immune-mediated, but the precise pathogenesis of most manifestations is unknown. Disease control by attacking the vector blackfly is not realistic for most areas of the world. Further, although ivermectin given at regular intervals may suppress disease, such a regimen is beyond the means of the health care infrastructure in much of the developing world. Thus, improved understanding of disease pathogenesis is clearly needed. This proposal is designed to establish a multidisciplinary, interactive program that capitalizes on the expertise of established investigators to apply the techniques of molecular biology and molecular immunology to human onchocerciasis. This is based upon a combined field-based clinical and basic immunology program of onchocerciasis research developed over the past 11 years in the U.S. and West Africa. Project 1 will identify individuals with ocular or skin disease and provide reagents to define antigens and epitopes associated with clinical disease at the molecular level, and test defined antigens for effect on cells from persons with disease. This basis for geographic variation in disease and the influence of ivermectin treatment on the immune response will be examined. Project 2 will identify and characterize clones encoding disease-associated antigens, and will examine the genetic basis for the difference between forest and savannah pathogenic epitopes. Project 3 will prepare T lymphocyte clones against disease-associated antigens; these clones will be utilized for T epitope mapping and functional studies of the most active antigens. Project 4 will examine recombinant antigens in the guinea pig model of keratitis and define pathogenic epitopes and MHC restriction of reactivity. Core A will serve Projects 1-4 with protein and peptide chemistry and epitope mapping expertise. Core B will provide the necessary starting materials for Projects 1, 2, 3, and 4. The goal of this multidisciplinary Program is to focus the extraordinary talent represented by this group of investigators on a disease problem that is not readily amenable to more limited approaches, with the objective of contributing to ultimate disease control.