IMMUNOREGULATION OF THE SCHISTOSOME EGG GRANULOMA

血吸虫卵肉芽肿的免疫调节

• 批准号: 3444456
• 负责人: DOV L BOROS
• 金额: $ 14.24万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 1987-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3444456
• 关键词: B lymphocyte; T lymphocyte; cellular immunity; delayed hypersensitivity; density gradient ultracentrifugation; humoral immunity; immunoglobulins; inflammation; macrophage; migration inhibition factor; schistosomiasis; thymectomy

This search project comprises the continued elucidation of the inflammatory, immunoregulatory and reparative aspects of the parasite egg-induced granulomas in murine schistosomiasis mansoni. Our long term objective is to elucidate the dynamics of cell-cell interation, idnetify and define the function of molecular mediators and enzymes which participate in the evolution and involution of thegranulomatous response. A better understanding of the regulation of inflammation, tissue damage and healing in the murine model will greatly improve the clinical handling of schistosomiasis. The research objectives are divided into 4 interrelated areas: I. Analysis of T cell circuitry active in the immunomodulation of the granuloma. This will be carried out with isolated subpopulations of splenic and granuloma T lymphocytes, Adoptive cell transfers, in vitro cell-cell interactions, the production and functional examination of soluble regulatory/amplifier molecules will be employed. II. Studies on the accessory/regulatory role of granuloma macrophages. Macrophages will be isolated from vigorous and modulated granulomas and their accessory role in the elicitation of SEA-specific secondary immune response will be examined. Production of activating and inhibitory substances by these macrophages will be tested. III. Studies on the presence and role of angiotensins I, II and prostaglandins in the granulomatous response. Vigorous and modulated granulomas will be assayed for the presence of angiotensins and prostaglandins which may play important roles in the inflammatory/regulatory aspects of the granulomatous response. The effect of immunomanipulationon the levels of these substances within the granulomas will be assayed. IV. Studies on the effect of immunomaipulation on liver collagen content and breakdown. Liver and granuloma collagen content as well as the presence of degradative neutral proteases in the virorous or modulated granulomas will be examined. The source of neutral proteases within the lesions will be localized. The class of degradative enzymes and their potential inhibitors will be identified. The effect of immunomanipulation on total collagen content, and activity of collagenease, elastase enzymes will be examined.

该搜索项目包括继续阐明 寄生虫的炎症、免疫调节和修复方面 小鼠曼氏血吸虫病虫卵诱发的肉芽肿。 我们的长期 目标是阐明细胞间相互作用的动态，idnetify 并定义分子介质和酶的功能 参与肉芽肿反应的演变和消退。 更好地了解炎症、组织损伤和 小鼠模型的愈合将大大改善临床处理 血吸虫病。 研究目标分为4个相互关联的 领域： I. 免疫调节中活跃的 T 细胞回路分析 肉芽肿。 这将在孤立的亚群中进行 脾和肉芽肿 T 淋巴细胞，过继细胞移植，体外 细胞间的相互作用、细胞的产生和功能检查 将使用可溶性调节/放大器分子。 二.研究 肉芽肿巨噬细胞的辅助/调节作用。 巨噬细胞会 从剧烈和调节性肉芽肿中分离出来及其辅助作用 在引发 SEA 特异性二次免疫反应时 检查了。 通过这些物质产生激活和抑制物质 将测试巨噬细胞。 三． 存在及其作用的研究 血管紧张素 I、II 和前列腺素在肉芽肿反应中的作用。 将检测剧烈且经过调节的肉芽肿是否存在 血管紧张素和前列腺素可能在 肉芽肿反应的炎症/调节方面。 效果 免疫操作对体内这些物质的水平的影响 将检测肉芽肿。 四． 效果研究 免疫调节对肝脏胶原蛋白含量和分解的影响。 肝脏和 肉芽肿胶原蛋白含量以及降解中性的存在 将检查病毒性或调节性肉芽肿中的蛋白酶。 这 病变内中性蛋白酶的来源将被定位。 这 降解酶及其潜在抑制剂的类别 确定。 免疫操作对总胶原蛋白含量的影响， 并检查胶原酶、弹性蛋白酶的活性。