S. MANSONI: IMMUNE INDUCED SURFACE CHANGES

S. MANSONI：免疫引起的表面变化

• 批准号: 3135005
• 负责人: JOHN P CAULFIELD
• 金额: $ 15.96万
• 依托单位: SYNTEX (USA), INC.-RESEARCH DIVISION
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3135005
• 关键词: Schistosoma japonicum; Schistosoma mansoni; autoradiography; blood lipoprotein; carbohydrate structure; cell cell interaction; cell mediated cytotoxicity; cell transformation; chemical binding; eosinophil; gel electrophoresis; host organism interaction; human tissue; immunochemistry; immunological substance; immunotherapy; iodine; laboratory mouse; laboratory rabbit; membrane activity; membrane fusion; membrane proteins; microorganism genetics; microorganism immunology; neutrophil; protein sequence; protozoal vaccine; radionuclides; schistosomiasis; steroid metabolism; sterols; vaccines

This proposal is a competitive renewal to continue 12 years of work on Schistosoma mansoni. There are three major areas of interest each of which has three subprojects. The first area centers on the cercarial glycocalyx. The goals are to purify the glycocalyx to homogeneity, to fragment the purified glycocalyx, and to test the glycocalyx for its ability to protect mice from schistosome infection by preimmunization with the glycocalyx or its fragments. In addition, preparations of the glycocalyx that have been previously shown to increase adult worm burden will be tested for their ability to induce specific suppression. These experiments are potentially important in vaccine development. The second area of interest centers on interactions between human blood cells and schistosomula. We have previously proposed that schistosomula defend themselves against human effector cells by secreting monopalmitoyl lysophosphatidylcholine which lyses the attacking cells. We wish to test whether human monocytes adherent to the parasites show the effects of this compound in their membranes by fluorescence photobleaching recovery. Human eosinophils that have been activated with cytokines will be examined ultrastructurally to determine if they kill the parasite by the same mecha- nisms as inactivated eosinophils. Cultured eosinophils that have been activated and shifted to a hypodense phenotype will also be tested. The results will be quantitated morphometrically. In a third set of experiments, human monocyte-derived macrophages will be tested as effector cells in toxic reactions after exposure to a variety of mediators. For both monocytes and eosinophils the role of classes and subclasses of immunoglobulin prepared from patient sera in parasitic killing will be determined. These studies should define the potential capabilities of these two cell types and clarify the mechanism of parasite defense. The third area is concerned with the binding of human lipoproteins to the surface of schistosomula. The initial experiments will quantitate the binding and demonstrate its specificity. Then the ability of lipoproteins to inhibit antibody dependent cytotoxic reactions will be tested. Finally, the role of lipoproteins in worm sterol metabolism will be studied. These studies should establish whether lipoprotein binding is a defense mechanism for the parasite.

该提案是一项竞争性更新，旨在继续 12 年的工作 曼氏血吸虫。 共有三个主要兴趣领域，每个领域 拥有三个子项目。 第一个区域以尾蚴糖萼为中心。 目标是将糖萼纯化至均质，将糖萼片段化 纯化的糖萼，并测试糖萼的保护能力 通过用糖萼预免疫而免受血吸虫感染的小鼠或 它的碎片。 此外，糖萼的制剂已 先前显示会增加成虫负担的药物将被测试 诱导特异性抑制的能力。 这些实验有可能 在疫苗开发中具有重要意义。 第二个感兴趣的领域集中在人类血液之间的相互作用 细胞和血吸虫。 我们之前提出过血吸虫 通过分泌单棕榈酰来防御人类效应细胞 溶血磷脂酰胆碱可裂解攻击细胞。 我们希望测试 粘附在寄生虫上的人类单核细胞是否显示出这种效果 通过荧光光漂白恢复其膜中的化合物。 人类 将检查已被细胞因子激活的嗜酸性粒细胞 超微结构以确定它们是否通过相同的机械杀死寄生虫 Nisms 为失活的嗜酸性粒细胞。 培养的嗜酸性粒细胞 激活并转变为低密度表型也将被测试。 这 结果将通过形态测定进行定量。 在第三组中 实验中，人类单核细胞来源的巨噬细胞将作为效应器进行测试 细胞在接触多种介质后发生毒性反应。 为了 单核细胞和嗜酸性粒细胞的类别和亚类的作用 从病人血清中制备的用于杀灭寄生虫的免疫球蛋白 决定。 这些研究应该定义潜在的能力 这两种细胞类型并阐明了寄生虫的防御机制。 第三个领域涉及人类脂蛋白与 血吸虫表面。 最初的实验将量化 结合并证明其特异性。 那么脂蛋白的能力 将测试抑制抗体依赖性细胞毒性反应。 最后， 将研究脂蛋白在蠕虫甾醇代谢中的作用。 这些 研究应确定脂蛋白结合是否是一种防御机制 对于寄生虫。