IN VITRO S. MANSONI FECUNDITY AND GRANULOMA FORMATION

曼索尼沙门氏菌的体外繁殖力和肉芽肿形成

• 批准号: 3444490
• 负责人: S M PHILLIPS
• 金额: $ 3.01万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-12-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3444490
• 关键词: Schistosoma mansoni; T lymphocyte; anthelmintics; athymic mouse; cell adhesion; cell fusion; cell population study; cellular immunity; clone cells; collagen; drug screening /evaluation; egg /ovum; fluorescence microscopy; fluorescent dye /probe; granuloma; helminthic antigen; histochemistry /cytochemistry; histopathology; host organism interaction; immunologic assay /test; interleukin 1; laboratory mouse; leukocyte activation /transformation; lymphokines; macrophage; monoclonal antibody; protein biosynthesis; radiotracer; schistosomiasis; tissue /cell culture

Morbidity, in schistosomiasis, is influenced by granuloma formation and fibrosis. The in vitro model of granuloma formation was developed in this laboratory to characterize the cellular and molecular mechanisms responsible for activation and control of granuloma formation and fibrogenesis. This system will be used to quantitatively analyze the kinetics and mechanisms of cellular recruitment and collagen synthesis in murine schistosomiasis. The usefulness of this model has been augmented by 3 recent developments: 1. SEA-reactive T cell clones, which produce granulomas in vitro and bear idiotypic receptors for S. mansoni antigens. These clones will be employed to examine specific inter- and intracellular signals. Particular emphasis will be placed on defining the effects of T cell factors on initial granuloma formation, fibroblast proliferation, and collagen synthesis. 2. Defined bead granulomas; Polystyrene beads, to which antigen has been covalently bound, serve as nidi of granuloma formation, permitting characterization of antigenic epitopes and conditions of cellular activation. 3. Liver function tests; Application of the aminopyrine breath test, serum bile acid determination, and other more conventional assays will facilitate quantitative investigation of the pathophysiologic effects of schistosomiasis on liver function. Thus, it will be become possible to correlate a variety of immunopathologic parameters of granuloma formation and fibrosis with quantitative indices of morbidity. The in vivo significance of these observations will be assessed through the adoptive transfer of cells and/or antigen coated beads to normal and S. mansoni infected animals. Once mechanisms are identified, a rational immunotherapeutic approach to granuloma modulation might be developed. Toward this end, we will assess the feasibility of immunizing with polyclonal T cell blasts, lines, or monoclonal T cells to elicit specific negative regulation of granuloma formation. These studies will provide valuable information with respect to basic mechanisms of granuloma formation as well as to the long range goal of reduced morbidity in schistosomiasis.

在血吸虫病中，发病率受肉芽肿形成和 纤维化。在此中开发了肉芽肿的体外模型 实验室表征细胞和分子机制 负责激活和控制肉芽肿的形成和 纤维发生。 该系统将用于定量分析 细胞募集和胶原蛋白合成的动力学和机制 鼠血吸虫病。 该模型的实用性已被增强 3最近的发展：1。产生的海洋反应性T细胞克隆 体外颗粒瘤，并为曼氏链球菌抗原带有愚蠢的受体。 这些克隆将用于检查特定的细胞间和细胞内 信号。 将特别强调定义T的影响 初始肉芽肿形成，成纤维细胞增殖和 胶原蛋白合成。 2。定义的珠颗粒；聚苯乙烯珠， 哪些抗原已共价结合，用作肉芽瘤的NIDI 形成，允许表征抗原表位和条件 细胞激活。 3。肝功能测试；应用 氨基肾上腺素的呼气测试，血清胆汁酸的测定等 常规测定将促进对 血吸虫病对肝功能的病理生理作用。 因此，它 将有可能关联多种免疫病理学 肉芽肿形成和纤维化的参数，具有定量指数 发病率。 这些观察结果的体内意义将被评估 通过细胞和/或抗原涂层珠的继产传递到 正常和曼氏链球菌感染动物。 一旦确定了机制， 颗粒瘤调节的理性免疫治疗方法可能是 发达。 为此，我们将评估免疫的可行性 与多克隆T细胞爆炸，线或单克隆T细胞一起引起 特定的颗粒状形成负调节。 这些研究会 提供有关肉芽肿的基本机制的宝贵信息 形成以及远距离降低发病率的远距离目标 血吸虫病。