THE IDIOTYPIC REGULATION OF RESISTANCE TO SCHISTOSOMIASI

抗血吸虫病的独特调控

• 批准号: 3444674
• 负责人: S M PHILLIPS
• 金额: $ 22.22万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3444674
• 关键词: B lymphocyte; antibody formation; hybridomas; monoclonal antibody; radioimmunoassay; schistosomiasis

These studies are designed to investigate the role of idiotypic regulation in the development and expression of resistance to schistosomiasis. Two strategic or long term goals are sought: 1. The elucidation of possible alternative modes of immunization which may "improve on nature"; 2. The establishment of possible methods to monitor the development of clinical resistance without the requirement of invasive challenge/perfusion procedures. To accomplish these strategic goals, animals will first be infected with S. mansoni cercariae and sacrificed at serial intervals. They will be assessed, for the presence of factors such as antibody or cells with the ability to modulate, at the idiotypic level, specific anti-schistosomal responses related to immunity. Once these constituents are demonstrated, they will be precisely defined both phenotypically and functionally to more fully assess the constituents and establish interactions in an idiotypic regulatory network. In vivo and in vitro assays will be correlated to the resistance status of the donor, determined by challenge. Animals will then be exposed to irradiated cercariae to induce active immunity and thus enable measurement of the sequential development of the participants in the immunoregulatory network. Following the establishment of the components and optimal assays, isolated constituents of a protective network will be specifically utilized to enhance or suppress the development of protective immunity. These studies will demonstrate the biological relevance of the network to resistance. The optimal mode of monitoring the interactions of that network may provide a practical method to ascertain the status of in vivo immunity. Ultimately, the network will be perturbed, in a directed manner, to optimize protective immunity. The various defined idiotypic components-both cellular and humoral-will be selectively utilized alone or in combination. Thus these studies represent an important new approach to the induction and monitoring of resistance to schistosomiasis.

这些研究旨在研究惯用型调节的作用 在对血吸虫病的抗性的发展和表达中。 二 寻求战略或长期目标：1。 免疫的替代模式可能会“对自然有所改善”； 2 建立可能监测临床发展的方法 不需要侵入性挑战/灌注的抵抗力 程序。 为了实现这些战略目标，动物首先是 感染了曼氏链球菌，并以串行间隔牺牲。 将对它们进行评估，因为存在抗体或 具有调节特定水平的能力的细胞 与免疫相关的抗固定体反应。 一旦这些成分 已证明，它们将在表型和 在功能上更充分地评估成分并建立 白痴调节网络中的相互作用。 体内和体外 测定将与确定的捐赠者的抵抗状态相关 通过挑战。 然后，动物将暴露于辐照的cercariae中 诱导主动免疫，从而实现顺序测量 免疫调节网络参与者的发展。 下列的 建立组件和最佳测定法，孤立 保护网络的成分将被专门用于 增强或抑制保护性免疫的发展。 这些研究 将证明网络与抗性的生物学相关性。 监视该网络交互的最佳模式可能会提供 一种确定体内免疫状态的实际方法。 最终，网络将以指示的方式受到干扰 优化保护性免疫。 各种定义的白痴 细胞和体液 - 将单独使用的组成部分和体液愿意使用或 结合。 因此，这些研究代表了一种重要的新方法 诱导和监测对血吸虫病的抗性。