HUMORAL & CELL-MEDIATED IMMUNITY IN DEVELOPMENT OF BRONCHIAL HYPERRESPONSIVENESS

哮喘是一种呼吸道疾病，大多数患者表现为 对包括药物在内的一系列诱因的高反应性(BHR) 比如乙酰甲胆碱。哮喘最常与呼吸道有关。 炎症，但将哮喘与炎症联系起来的证据，尽管 令人信服，是间接的。这个项目的长期目标是 旨在阐明体液免疫和细胞免疫在人类免疫中的作用 BHR的发展，特别是IgE抗体和特异性T细胞的作用 淋巴细胞亚群。了解小鼠免疫系统及其功能 区分和明确遗传差异的能力 产生IgE抗体为使用该物种提供了明显的优势 而不是其他BHR动物模型。我们现在已经开发出一种实验性的 吸入抗原致小鼠BHR模型的建立。在缺席时 在佐剂的作用下，BALB/c小鼠产生与免疫球蛋白E抗体相关的快速反应 支气管周相关淋巴结(PBLN)明显增多 以及抗原反应性T细胞的数量。此外，在体内(身体)使用 体积描记)和体外(气管平滑肌收缩)分析， 我们证明，吸入抗原致敏的小鼠会发生BHR。 在这个项目中，我们将确定局部和系统免疫的作用。 在BHR的发病机制中起重要作用。我们将研究BHR在高等教育中的发展 和低IgE反应性小鼠，在裸鼠和以下动物中 过继转移先前致敏的不同淋巴细胞亚群 动物或不同表型的抗原特异性T细胞克隆。我们会 直接勾画IgE抗体在被动转移中的作用 实验以及确定T细胞受体Vbeta的使用是否 仅限于致敏或产生免疫球蛋白E的动物。这些研究将 提供有关T-B作用的新的重要信息 相互作用与IgE在BHR发病机制中的作用

Asthma is a disease of the airways, where most patients demonstrate bronchial hyperresponsiveness (BHR) to a range of triggers including drugs such as methacholine. Asthma is most often associated with airway inflammation but the evidence associating asthma with inflammation, albeit compelling, is circumstantial. The long term objectives of this project are to delineate the role of humoral and cell-mediated immunity in the development of BHR, especially the role of IgE antibody and specific T- lymphocyte subsets. Knowledge of the murine immune system, its functional compartmentalization and defined genetic differences in the ability to generate IgE antibodies offers distinct advantages for using this species over other animal models of BHR. We have now developed an experimental model of BHR in mice following exposure to inhaled antigen. In the absence of adjuvant, BALB/c mice develop a brisk IgE antibody response associated with a marked increase in the peri-bronchial associated lymph nodes (PBLN) and numbers of antigen-reactive T cells. Moreover using in vivo (body plethysmography) and in vitro (tracheal smooth muscle contraction) assays, we demonstrate that mice sensitized by inhalation of antigen develop BHR. In this project we will determine the role of local and systemic immunity in the pathogenesis of BHR. We will study the development of BHR in high and low IgE responding mice, in athymic (nude) mice, as well as following adoptive transfer of distinct lymphocyte subsets from previously sensitized animals or antigen-specific T-cell clones of different phenotypes. We will directly delineate the role for IgE antibody in passive transfer experiments as well as determining whether T-cell receptor Vbeta usage is restricted in sensitized or IgE-producing animals. These studies will provide new and important information concerning the role of T-B interactions and IgE in the pathogenesis of BHR.