S. MANSONI VITELLOGENESIS AND GRANULOMA FORMATION

S. 曼索尼卵黄发生和肉芽肿形成

• 批准号: 2060173
• 负责人: S M PHILLIPS
• 金额: $ 31.16万
• 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 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2060173
• 关键词: Schistosoma mansoni; T lymphocyte; anthelmintics; athymic mouse; biological signal transduction; cell adhesion; cell cell interaction; cell fusion; cell population study; cellular immunity; collagen; confocal scanning microscopy; egg /ovum; fluorescence microscopy; fluorescent dye /probe; gene expression; genetic regulatory element; granuloma; helminthic antigen; histochemistry /cytochemistry; histopathology; host organism interaction; immunologic assay /test; immunoregulation; in situ hybridization; interleukin 1; laboratory mouse; leukocyte activation /transformation; lymphokines; molecular cloning; monoclonal antibody; protein biosynthesis; radiotracer; schistosomiasis; tissue /cell culture

In schistosomiasis, the deposition of parasite ova within tissues is the initial event in a complex pathophysiological cascade which is characterized by granuloma formation and term- inates in hepatic fibrosis and related clinical sequela. We have developed an in vitro model of granuloma formation which has provided a vehicle to study granuloma formation and fibrosis and the regulation of these phenomena. These studies will analyze the cellular constituents of granulomatous hypersen-sitivity and their modes of interaction at the molecular level. To accomplish this goal four major approaches are anticipated: 1. The use of collagen matrix beads: These beads permit the in vitro development of a three-dimensional recapitulation of the in vivo granuloma and facilitate the evaluation of cellular constituents, interaction and the role of antigens, growth, chemotactic, and adherence factors in granuloma formation. 2. Assessment of the role of T regulatory factors: Evidence for the production and role of defined "T regulatory" factors such as interleukins, interferon, and growth factors will be sought. In addition, regulatory factors, bearing specific phenotypic determinants and an antigen receptor, have been produced from the T cells obtained from infected mice. These factors specifically inhibit in vitro and in vivo granuloma formation; when analyzed for structure and function the factors promise to be important regulatory molecules. 3. T cell cloning technology: We have previously reported T clones capable of inducing in vitro granuloma and, more recently, have developed technology to produce suppressor T clones. These T clones will be used to analyze specific interactions of the regulatory populations. In addition, they will be used to define immunogenic epitopes relevant toward granuloma formation or its regulation. 4. Application of molecular biological analysis: The ultimate goal of these studies is to understand the specific molecular signals for the development and modulation of granulomatous hypersensitivity for the production and activation of various T regulatory and molecules or pathways is anticipated using multiple modes of analyses including a Confocal microscope. This information will be applied to the long range goal of reducing morbidity in schistosomiasis by directed immunomodulation of granulomatous hypersensitivity.

在血吸虫病中，寄生虫卵子的沉积 组织是复杂的病理生理学中的初始事件 级联的特征是形成肉芽肿和术语。 肝纤维化和相关临床后遗症。 我们有 开发了一种体外模型的肉芽肿形成模型 提供了研究肉芽肿形成和纤维化以及 这些现象的调节。 这些研究将分析 肉芽肿性超血性和的细胞成分 它们在分子水平上的相互作用模式。 完成 预计这一目标的四个主要方法：1。 胶原基质珠：这些珠允许体外 开发体内三维概括 肉芽瘤并促进细胞成分的评估 相互作用和抗原，生长，趋化性和 颗粒瘤形成中的依从因子。 2。评估 调节因素的作用：生产的证据和 定义的“ T调节”因素（例如白介素）的作用， 干扰素和生长因素将被寻求。 此外， 调节因素，具有特定表型决定因素和 从获得的T细胞中产生的抗原受体 来自感染的小鼠。 这些因素特别抑制了体外 和体内肉芽肿的形成；分析结构和 功能这些因素承诺将是重要的调节 分子。 3。t细胞克隆技术：我们以前有 据报道T克隆能够诱导体外颗粒瘤和 最近，开发了生产抑制剂的技术 克隆。 这些T克隆将用于分析特定 监管人群的相互作用。 另外，他们 将用于定义与 肉芽瘤形成或其调节。 4 分子生物学分析：这些的最终目标 研究是为了了解 肉芽肿性超敏反应的发展和调节 各种调节的生产和激活 预计分子或途径将使用多种模式 包括共聚焦显微镜的分析。 这些信息将 应用于降低发病率的远距离目标 血吸虫病通过颗粒状的定向免疫调节 高敏性。