The Immune Response in Mast Cell Deficient Mice

描述（由申请人提供）：在特定的社会、压力和疾病状态下，大脑肥大细胞的数量增加。同样重要的是，发现脑肥大细胞可以穿过血脑屏障。尽管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。肥大细胞是异质的，它们的介质含量依赖于它们的微环境，这表明脑肥大细胞应该作为一个独特的群体来研究——与外周细胞不同。本申请提出开发一个小鼠模型，该模型将用于理解大脑肥大细胞的现象学和功能后果。初步数据表明，肥大细胞缺陷动物对细菌感染缺乏完全的急性期反应（APR）。为了研究肥大细胞在免疫应答中的作用，我们探讨了两种社会/行为/内分泌条件下，大脑肥大细胞数量增加的情况：同居模式和压力模式。接下来，我们验证了先前暴露（增加脑肥大细胞数量）导致肥大细胞丰富的脑位点对免疫系统挑战的反应改变的假设。具体来说，我们想知道当肥大细胞在大脑中的数量增加时，肥大细胞的数量和激活状态是否会增加。为了验证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T细胞监视的改变。我们建议在肥大细胞缺陷小鼠、野生型幼崽和肥大细胞重组动物中验证这些假设。这一应用将确定肥大细胞是否在大脑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.