ASTHMA, ALLERGIC AND IMMUNOLOGIC DISEASES COOP RES CTR

该AAIDCRC计划提案代表了 目前已获CIRID资助。五个项目采用现代 分子、基因和细胞技术，试图了解 正常和异常免疫反应的基本病理生理学。 三 项目（洛，Murphy和Unanue）使用鼠，而其余两个项目 直接与人的材料（卢布林和卓别林）。 该计划的目标是 阐明生物学机制，决定的结果， 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。 博士洛的项目研究了CD 4分子如何参与免疫反应。 辅助性T细胞发育和功能的生理学， T细胞受体转基因、CD 4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 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抗李斯特菌感染 使用SCID小鼠模型，一个强大的系统， 特异性免疫反应。 卢布林博士将研究 补体调节蛋白，另一个重要的组成部分， 抗原特异性免疫反应。卓别林医生会集中精力 在识别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 与圣路易斯哮喘患者一起开展示范和教育项目 他们在过去四年里一直在工作的人。

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.