IMMUNOREGULATION OF THE SCHISTOSOME EGG GRANULOMA

这项搜索计划包括继续阐明 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导的肉芽肿。我们的长期计划 目的是阐明细胞-细胞相互作用的动力学 并定义了分子介体和酶的功能 参与肉芽肿性反应的进化和消退。 更好地了解炎症、组织损伤和 在小鼠模型中的愈合将极大地改善临床处理 血吸虫病。研究目标分为四个相互关联的部分 研究领域：I.免疫调节中活跃的T细胞回路的分析 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-细胞相互作用、细胞因子的产生和功能检测 将使用可溶的调节/放大分子。二、关于 肉芽肿巨噬细胞的辅助/调节作用。巨噬细胞将 从强健和调节性肉芽肿中分离出来及其辅助作用 在激发SEA特异性二次免疫反应时 检查过了。这些细菌产生活性物质和抑制物质 巨噬细胞将接受测试。三、关于……的存在和作用的研究 肉芽肿性反应中的血管紧张素I、II和前列腺素。 将对活跃的和调制的肉芽肿进行检测，以确定是否存在 血管紧张素和前列腺素可能在血管紧张素转换酶 肉芽肿反应的炎症/调节方面。其效果 免疫调节对体内这些物质水平的影响 将化验肉芽肿。四、关于防病治病效果的研究 免疫调节对肝脏胶原含量和分解的影响。肝和 肉芽肿胶原含量以及降解性中性物质的存在 对病理性或调节性肉芽肿中的蛋白水解酶进行检测。这个 皮损内中性蛋白酶的来源将被定位。这个 一类降解酶及其潜在的抑制剂将是 已确认身份。免疫调节对总胶原含量的影响 并检测胶原酶、弹性酶的活性。

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.