ASTHMA, ALLERGIC AND IMMUNOLOGIC DISEASES COOP RES CTR

哮喘、过敏和免疫性疾病 COOP RES CTR

• 批准号: 3548085
• 负责人: Max Dale Cooper
• 金额: $ 52.09万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3548085
• 关键词: asthma; cooperative study; immunoglobulin E; immunoglobulin genes

The Asthma, Allergic, and Immunologic Diseases Cooperative Research Center of the University of Alabama at Birmingham (UAB) is a multidisciplinary effort, involving faculty and staff of the clinical Departments of Medicine and Pediatrics, and the basic science Department of Microbiology. The primary focus is the elucidation of pathogenetic mechanisms operative in allerigc diseases of immune function. The Demonstration and Education Research component will focus on means to increase the effectiveness of educational interventions in improving asthma management. The BioMedical Research Component is composed of four integrated research projects designed to pursue experimental leads gained in earlier studies. As most of the investigators are actively involved in the care of patients with immunologic diseases, the program provides a working interface between basic and applied immunology. Atopic diseases result from the release of mediators of inflammation, a process associated with aggregation of high affinity receptors for lgE on the surface of mast cells (Fc-epsilon-RI). Project 1 will focus on phospholipase C-gamma1 isozymes that have been recently shown to be activated following Fc-epsilon-RI aggregation. Mechanisms of substrate hydrolysis and signal transduction will be studied. Project 2 will examine the hypothesis that susceptibility to atopic disease results from premature activation of the IgE response in the fetus. The composition of the IgE antibody repertoire will be determined as a function of ontogeny. Infants at high risk for atopic disease will be identified through recruitment of pregnant women in our allergy clinics and their cord blood IgE repertoire will be examined. Project 3 will focus on analysis of the molecular mechanisms that contribute to the immature phenotype of sIgA+ cells that are seen patients with IgA deficiency (IgAD) and in normal newborns. These cells will be purified by a newly developed combination of sorting techniques for analysis of the extent of C-mu deletion, a prerequisite for class switch recombination. The cells will also be examined for their responses to cytokines and to purified mixtures of T and B cell subpopulations. In order to gain further insight into host factors that can compensate for lgA deficiency, a mutant mouse model lacking lgA will be created. Abnormalities in thymic development may contribute to both atopy and lgA deficiency. In Project 4, the mechanism by which abnormal expression of the fas apoptosis antigen contributes to the loss of T cell tolerance in lpr mice will be studied.

哮喘、过敏和免疫疾病合作研究中心 亚拉巴马大学伯明翰分校（UAB）是一个多学科的 努力，涉及教师和工作人员的临床部门， 医学和儿科学，以及微生物学基础科学部门。 主要的焦点是阐明发病机制的运作 过敏性疾病的免疫功能。示范与教育 研究部分将侧重于如何提高 教育干预改善哮喘管理。生物医学 研究部分由四个综合研究项目组成 旨在追踪早期研究中获得的实验线索。因为大多数 的研究者积极参与患者的护理， 免疫疾病，该计划提供了一个工作界面之间 基础和应用免疫学特应性疾病是由于 炎症介质，一个与高密度脂蛋白聚集相关的过程， 肥大细胞表面上IgE的亲和受体（Fc-RI-RI）。 项目1将重点关注磷脂酶C-γ 1同工酶， 最近显示在Fc-epsilon-RI聚集后被激活。 底物水解和信号转导的机制将被 研究了项目2将检验易感性的假设 特应性疾病是由过敏性疾病中IgE反应的过早激活引起的。 胎儿IgE抗体库的组成将是 是由个体发育决定的特应性皮炎高危婴儿 疾病将通过招募孕妇在我们的 过敏诊所和他们的脐带血IgE库将被检查。 项目3将侧重于分析分子机制， 导致患者体内sIgA+细胞的不成熟表型， 伊加缺乏症（IgAD）和正常新生儿。这些细胞将 通过新开发的分选技术的组合进行纯化， 分析C-mu缺失的程度，是类别转换的先决条件 重组还将检查细胞对以下物质的反应： 细胞因子以及T和B细胞亚群的纯化混合物。在 为了进一步了解可以补偿的主机因素， IgA缺陷，将产生缺乏IgA的突变小鼠模型。 胸腺发育异常可能与特应性和IgA有关 缺陷 在项目4中，通过异常表达的机制， Fas凋亡抗原导致T细胞耐受性的丧失， 将研究LPR小鼠。