ORGANIZATION OF THE IMMUNE SYSTEM IN THE HUMAN FEMALE REPRODUCTIVE TRACT

人类女性生殖道(FRT)组织被定义为 以及影响免疫细胞功能的有组织的微环境。 此外，性类固醇激素，雌二醇和孕酮，有一个 控制对神经传入和传出臂的影响 免疫系统。迄今为止，对人类粘膜免疫系统的研究已经 这在很大程度上依赖于对分离细胞的研究，而这种方法并不 允许评估组织架构的影响和 微环境。此外，对猪的免疫系统的研究相对较少。 已经进行了人体首次放射治疗。因此，我们目前对 免疫系统在这一关键阶段的组织和功能 重要的器官系统显然是不充分的，我们对 内分泌对这些组织的免疫功能有影响。 拟议的研究将使用新的原位技术，这利用了 活体组织切片，以验证性激素调节的假设 不同微环境中免疫细胞的组织和功能 FRT的子宫内膜(EM)。特别是，我们假设 在月经周期中，性激素和细胞因子的作用令人担忧 在EM内调节免疫细胞的组织和功能 首次公开募股。更具体而言，我们会： 1)确定T、B淋巴细胞和髓系细胞的组织 在FRT的EM的不同微环境中以及这是如何 随月经周期的不同而不同。 2)确定负责监管建筑的机制 关于细胞增殖作用的EM重塑， 细胞凋亡、细胞因子和黏附分子。 3)确定性激素和细胞因子对细胞毒T细胞的作用 和髓系细胞在不同的EM微环境中的功能。 这些研究的结果应该会为 FRT免疫系统的组织和功能，而FRT又 将加深我们对首次登记税对 性传播疾病，并在合理设计 针对这些疾病的免疫接种方案。这些研究还将 提供重要信息，有助于评估 导致妇科恶性肿瘤和其他疾病的机制 FRT，包括子宫内膜异位症。

The tissues of the human female reproductive tract (FRT) exhibit defined and organized microenvironments that influence immune cell function. Furthermore, the sex steroid hormones, estradiol and progesterone, have a controlling influence on both the afferent and the efferent arms of the immune system. To date, studies of the human mucosal immune system have largely relied on the study of isolated cells, an approach which does not allow evaluation of the influence of tissue architecture and microenvironment. Moreover, relatively few studies of the immune system of the human FRT have been carried out. Thus, our current understanding of the organization and function of the immune system in this critically important organ system is clearly inadequate, as is our understanding of the endocrine influences on immunity in these tissues. The proposed studies will use novel in situ techniques, which utilize viable tissue sections, to test the hypothesis that sex hormones regulate immune cell organization and function in the different microenvironments of the uterine endometrium (EM) of the FRT. In particular, we postulate that during the menstrual cycle, sex hormones and cytokines act in concern to regulate the organization and function of immune cells within the EM of the FRT. More specifically, we will: 1) Determine the organization of T and B lymphocytes and myeloid cells within the different microenvironments of the EM of the FRT and how this varies with stage of the menstrual cycle. 2) Identify the mechanisms responsible for the regulation of architectural remodeling in the EM with regard to the role of cell proliferation, apoptosis, cytokines and adhesion molecules. 3) Determine the role of sex hormones and cytokines on cytotoxic T cell and myeloid cell function in the different microenvironments of the EM. The results of these studies should provide valuable insights into the organization and function of the immune system of the FRT, which in turn will enhance our understanding of the susceptibility of the FRT to sexually transmitted diseases, and be of value in the rational design of regimens for immunization against these diseases. These studies will also contribute important information useful for the evaluation of the mechanisms leading to gynecological malignancies and other diseases of the FRT, including endometriosis.