IMMUNOREGULATION OF THE SCHISTOSOME EGG GRANULOMA

这项研究计划包括继续阐明 寄生虫的炎症、免疫调节和修复方面 小鼠曼氏血吸虫虫卵诱导的肉芽肿 我们的长期 目的是阐明细胞间相互作用的动力学， 并定义了分子介质和酶的功能， 参与肉芽肿反应的演变和退化。 更好地理解炎症、组织损伤和 在小鼠模型中的愈合将大大改善临床处理， 血吸虫病 研究目标分为四个相互关联的部分 地区：I. 免疫调节中T细胞回路活性的分析 肉芽肿 这将与隔离的亚群进行 脾和肉芽肿T淋巴细胞，诱导细胞转移，体外 细胞与细胞的相互作用、细胞的产生和功能检查 将使用可溶性调节/放大分子。 二.研究 肉芽肿巨噬细胞的辅助/调节作用。 Macrology将 从活跃和调制的肉芽肿及其辅助作用中分离出来 在激发SEA特异性的二次免疫应答中， 考察 通过这些产生活化和抑制物质 将测试巨噬细胞。 三. 关于存在和作用的研究 血管紧张素I、II和胰高血糖素在肉芽肿反应中的作用。 将测定活力和调节的肉芽肿是否存在 血管紧张素和胰高血糖素，可能发挥重要作用， 肉芽肿反应的炎症/调节方面。 效果 的免疫操纵对这些物质的水平在 将对肉芽肿进行分析。 四. 影响的研究 免疫调节对肝胶原含量和分解的影响。 肝脏和 肉芽肿胶原蛋白含量以及存在降解中性 检查病毒性或调节性肉芽肿中的蛋白酶。 的 将定位病变内中性蛋白酶的来源。 的 一类降解酶及其潜在的抑制剂将是 鉴定 免疫操纵对总胶原含量的影响， 并检测胶原酶、弹性蛋白酶的活性。

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.