Genetic/Immunological Basis of Tuberculosis and Anergy

结核病和无反应性的遗传/免疫学基础

• 批准号: 6366017
• 负责人: JULIO Cesar DELGADO
• 金额: $ 12.87万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6366017
• 关键词: anergy; gene environment interaction; genetic polymorphism; genetic susceptibility; host organism interaction; human subject; immunogenetics; patient oriented research; southeast Asia; tuberculosis

DESCRIPTION (provided by applicant): The purpose of this Clinical Investigator Development Award is to prepare the candidate, Dr. Julio C. Delgado, MD, for a career as an independent investigator in infectious diseases with a special emphasis on the genetic and immunological mechanisms associated with susceptibility to tuberculosis infection. The applicant proposes a 5-year training and research program that will prospectively identify novel host factors that predispose individuals to develop pulmonary tuberculosis in a population from Cambodia and characterize the events associated with the anergic state induced by tuberculosis infection in the intact human host. In Specific Aim 1, he will test the hypothesis that HLA molecules are functionally associated with tuberculosis progression and differential immune response to PPD and whether polymorphisms of the promoter region of certain cytokines are associated with impaired immune response against tuberculosis infection. In Specific Aim 2 and 3, he will characterize immunological and chromatin structural mechanisms associated with anergy to PPD in a cohort of tuberculosis patients from Cambodia with persistent and specific lack of response to PPD. Tuberculosis infection and pathogenesis are the result of a balance between the virulence of a particular invading organism and the host immune response. Susceptibility to tuberculosis in human populations is likely to be due to a complex interaction between several genetic, immunological and environmental factors. The experiments proposed in this application would attempt to identify host genetic factors and unveil abnormal immunological mechanisms leading to increase risk of clinical tuberculosis disease. It is anticipated that these results will be useful in the development of genetic and immune therapeutic strategies to combat tuberculosis.

描述（由申请人提供）： 该临床研究者发展奖的目的是准备 候选人，医学博士Julio C. Delgado博士从事独立职业 传染病研究人员特别强调了遗传和 与结核病易感性相关的免疫机制 感染。 申请人提出了一项为期5年的培训和研究计划 将前瞻性地确定新颖的宿主因素，使个人易于 在柬埔寨的人群中发展肺结核并表征 与结核病感染引起的厌食状态相关的事件 在完整的人类宿主中。 在特定目标1中，他将检验以下假设。 HLA分子在功能上与结核病进展相关 对PPD的差异免疫反应以及启动子的多态性是否 某些细胞因子的区域与免疫反应受损有关 针对结核病感染。 在特定的目标2和3中，他会描述 免疫和染色质结构机制与厌食有关 来自柬埔寨的结核病患者队列的PPD， 具体缺乏对PPD的反应。 结核病感染和发病机理是 特定入侵的毒力之间平衡的结果 有机体和宿主免疫反应。 对结核病的敏感性 人口可能是由于几个人之间的相互作用 遗传，免疫学和环境因素。 提出的实验 该应用程序将试图识别宿主遗传因素和揭幕 免疫机制异常导致临床风险增加 结核病。 预计这些结果将在 遗传和免疫治疗策略的发展 结核。