ASTHMA, ALLERGIC AND IMMUNOLOGIC DISEASES COOP RES CTR

哮喘、过敏和免疫性疾病 COOP RES CTR

• 批准号: 3548095
• 负责人: DENNIS Y LOH
• 金额: $ 58.62万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3548095
• 关键词: asthma; immunity

This AAIDCRC program proposal represents a competitive renewal of the currently funded CIRID grant. The five proposed projects employ modern molecular, genetic, and cellular technologies to try to understand the basic pathophysiology of normal and abnormal immune response. Three projects (Loh, Murphy, and Unanue) use murine while the remaining two deal directly with human material (Lublin and Chaplin). The Program goal is to elucidate the biological mechanisms that determine the outcome of an immune response by studying the genetic basis of immunity, the molecular/cellular biology of helper T cells, and the nature of non- antigen specific components that participate in the inflammatory reaction. Dr. Loh's project deals with how the CD4 molecule participates in the physiology of the helper T cell development and function by using a combination of T cell receptor transgenic, CD4 knock-out, and mutant CD4 transgenic mice. Dr. Murphy's project concentrates on the determination of helper T cell subsets by studying the transcriptional regulation of important lymphokine genes. Dr. Unanue will study the nature of macrophage activation and lymphokine production against Listeria infection using the SCID mouse model, a powerful system to dissect non-antigen specific immune response. Dr. Lublin will study the biology of the complement regulatory proteins, another important component of the non- antigen specific immune response. Dr. Chaplin will concentrate his efforts in identifying immunologically relevant genes in the HIA gene complex using reverse genetics and analysis of relevant patient populations. Finally, Dr. James Wedner and his colleagues will continue with their Demonstration and Education projects with the St. Louis asthmatic population that they have been working with for the last 4 years.

这项AAIDCRC计划提案代表着对 目前由CIRID拨款。这五个拟议的项目使用了现代化的 分子、遗传和细胞技术试图理解 免疫反应正常和异常的基本病理生理学。三 项目(Loh，Murphy和Unanue)使用鼠标，而剩下的两个项目 直接使用人类材料(卢布林和卓别林)。该计划的目标是 阐明决定一种疾病转归的生物学机制 免疫反应通过研究免疫的遗传基础， 辅助性T细胞的分子/细胞生物学，以及非 参与炎症反应的抗原特异性成分。 陆博士的项目涉及到CD4分子如何参与 辅助性T细胞发育和功能的生理学研究 T细胞受体转基因、CD_4基因敲除和突变CD_4的组合 转基因小鼠。墨菲博士的项目集中在确定 通过研究辅助性T细胞亚群的转录调控 重要的淋巴因子基因。Unanue博士将研究 巨噬细胞活化和淋巴因子产生对抗李斯特菌感染 使用SCID小鼠模型，一个强大的系统来解剖非抗原 特异性免疫反应。卢布林博士将研究 补体调节蛋白，非补体的另一个重要组成部分 抗原特异性免疫反应。卓别林博士将集中精力 在鉴定HIA基因复合体中的免疫相关基因方面 使用反向遗传学和相关患者群体的分析。 最后，詹姆斯·韦德纳博士和他的同事们将继续他们的 圣路易斯哮喘患者的示范和教育项目 他们在过去4年里一直在与之共事的人群。