S MANSONI: IMMUNE INDUCED SURFACE CHANGES

S MANSONI：免疫引起的表面变化

• 批准号: 3444871
• 负责人: JOHN P CAULFIELD
• 金额: $ 24.42万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1989-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3444871
• 关键词: autoradiography; cell cell interaction; gel electrophoresis; histocompatibility antigens; host organism interaction; immunochemistry; membrane activity; membrane fusion; microorganism immunology; neutrophil; radiotracer

This proposal has three major goals, all of which center on the surface of the human parasite Schistsosoma mansoni. First, the cercarial glycocalyx will be analyzed biochemically and immunologically in order to test its suitability as a candidate for a vaccine. The glycocalyx is highly antigenic, reacts with a protective mnonoclonal antibody, and is a mildly acidic glycoprotein that is over half carbohydrate. The glycocalyx will be purified, analyzed, fragmented and both the intact molecule and fragments will be tested for their ability to protect mice from schistosome infections. A second goal is to determine how the parasite protects itself from attack by cells of the host's immune system. In particular, the parasite lyses human granulocytes and acquires host membrane components. The mechanism of lysis will be explored with fluorescence photobleaching recovery techniques and the mechanism of host antigen acquisition with electron microscopic immunocytoochemnistry and freeze fracture. If these mechanism can be determined, the phenomena may be inhibited therapeutically with a resulting decrease in infection. Finally, since the surface of the parasite is syncytium covered by two lipid bilayers, the outer of which appears to contain very little protein, the lipid composition and biosynthesis of the surface will be examined by radiolabeling and HPLC. Many properties of the parasite surface can be attributed potentially to its lipids. Knowledge of the lipid makeup and turnover of the surface membranes may lead to the ability to produce biochemical alterations in these membranes which make the worm susceptible to immune killing.

该提案有三个主要目标，所有这些目标都集中在表面上， 人类寄生虫曼氏血吸虫 首先是尾蚴的糖萼 将进行生物化学和免疫学分析，以测试其 作为疫苗候选物的适宜性。 糖萼高度 抗原性，与保护性单克隆抗体反应，是一种温和的 超过一半碳水化合物的酸性糖蛋白。 糖萼将是 纯化、分析、片段化，完整分子和片段 将测试它们保护小鼠免受病毒感染的能力 感染. 第二个目标是确定寄生虫如何保护自己 免受宿主免疫系统细胞的攻击 特别是 寄生虫裂解人粒细胞并获得宿主膜成分。 用荧光光漂白法探讨其裂解机理 恢复技术和宿主抗原获得机制 电镜免疫细胞化学和冷冻骨折。 如果这些 可以确定机制，可以治疗性地抑制该现象 从而减少感染。 最后，由于表面 寄生虫是由两个脂质双层覆盖的合胞体，外层 似乎含有很少的蛋白质，脂质成分和 将通过放射性标记和HPLC检查表面的生物合成。 寄生虫表面的许多特性可能归因于 它的脂质。 了解表面的脂质组成和周转 膜可能导致产生生物化学改变的能力， 这些膜使蠕虫易于被免疫杀死。