The Immune Response in Mast Cell Deficient Mice

描述（由申请人提供）：脑肥大细胞的数量在特定的社会，压力和疾病状态下增加。同样重要的是，发现脑肥大细胞可以穿过血脑屏障。虽然肥大细胞以其介导过敏反应的作用而闻名，但越来越明显的是，它们在防御细菌感染方面也起着保护作用。肥大细胞是异质性的，它们的介质含量取决于它们的微环境，这表明脑肥大细胞应该作为一个独特的群体进行研究-与外周中的肥大细胞不同。本申请提出开发小鼠模型，其将用于理解脑中肥大细胞的现象学和功能后果。初步数据表明，肥大细胞缺乏动物缺乏一个完整的急性期反应（APR）细菌感染。为了研究肥大细胞参与安装的免疫反应，我们探讨了2个社会/行为/内分泌条件下，其中脑肥大细胞群增加：同居范例和压力范例。接下来，我们测试的假设，即先前的暴露（这增加了脑肥大细胞的数量）的结果在肥大细胞丰富的大脑基因座的免疫系统的挑战改变响应。具体来说，我们问肥大细胞的数量，激活状态是否增加时，他们在大脑中的数量增加。为了检验脑肥大细胞具有免疫学后果的假设，我们确定肥大细胞数量的增加是否会导致肥大细胞丰富的脑区域中T细胞监视的改变。我们建议在肥大细胞缺陷小鼠，在其野生型同窝仔和肥大细胞重建的动物中测试这些假设。这项应用将确定肥大细胞是否在大脑中的免疫反应中发挥作用。

DESCRIPTION (provided by applicant): The number of brain mast cells increases under specific social, stressful, and disease states. Also important, is the discovery that brain mast cells can cross the BBB. Although mast cells are best known for their role in mediating allergic reactions, it has become increasingly evident that they also play a protective role in defense against bacterial infection. Mast cells are heterogeneous, and their mediator content is dependent on their microenvironment, suggesting that brain mast cells should be studied as a unique population - as distinct from those in the periphery. The present application proposes to develop a mouse model which will be used in understanding the phenomenology and functional consequences of mast cells in the brain. Pilot data indicate that mast cell deficient animals lack a complete Acute Phase Response (APR) to bacterial infection. To examine the involvement of mast cells in mounting an immune response, we explore 2 social/behavioral/endocrine conditions in which the brain mast cell population is augmented: a cohabitation paradigm and a stress paradigm. Next, we test the hypothesis that prior exposure (which increases brain mast cell numbers) results in altered response to challenge of the immune system in mast cell rich brain loci. Specifically, we ask whether the mast cell number, activation state is augmented when their numbers in the brain are elevated. To test the hypothesis that brain mast cells have immunological consequences, we determine if increased mast cell numbers results in altered T cell surveillance in mast cell rich brain regions. We propose to test these hypotheses in mast cell deficient mice, in their wild type littermates and in mast cell reconstituted animals. This application will determine whether mast cells play a role in mounting an immune response in the brain.