DENDRITIC CELLS, LPS AND ORAL MUCOSA

描述(摘自申请者的摘要)：口腔是一个“门户” 对于细菌、真菌和其他到达 呼吸道和胃肠道。这些区域的衬里是麦芽， 可以诱导对细菌物种的免疫力或口服耐受性。这个 被称为DC的抗原提呈细胞形成了一个离散的显微解剖结构 MALT Peyer氏斑中T细胞的组织，这对 启动和调节免疫反应。我们实验室的工作 其他人则建立了人类口腔粘膜作为树突状细胞的丰富储存库。 目前，我们对区议会的职能和组织了解甚少。 这些纸巾。这个R21应用程序提出了这样的假设，如果得到证实， 将支持一种新的模式--适应性免疫在几个 水平：(1)渗入口腔粘膜的不同DC亚群；(2)TLRs 表达的；(3)遇到的抗原。我们的总体假设是 人口腔黏膜树突状细胞在适应性调节中的关键作用 对特定抗原的免疫反应。次假设是：(1)截然不同 树突状细胞亚群在牙周/颊中的不同微解剖部位 (2)这些DC亚群对内毒素和其他因子的反应不同 通过表达抗原选择性TLR2和TLR4而产生的抗原；以及 (3)T细胞对抗原的反应受DC反应性的调节。这个 本申请提出了以下目标：目标1：表征DC 在健康和疾病中渗透到人类口腔粘膜的亚群；和目标2： 确定DC亚群调节T细胞应答的能力 体外抗原。公安局已经组建了一支调查小组， 在微生物学、口腔病理学/口腔医学、免疫组织化学、 内毒素的纯化/鉴定、DC/朗格汉斯细胞功能和T细胞 功能来进行这些研究。调查人员都在 达拉斯校区贝勒医疗中心医院，包括贝勒学院 牙科-TAMUS和贝勒免疫研究所。它是 希望这项研究将促进我们对获得性免疫如何 微生物抗原在粘膜水平上被启动和调节。我们的 短期目标是获得足够的初步数据/出版物，以 协助成功提交R01建议书(S)。我们的长期合作 目标是将这项研究发展到关于DC的计划项目的水平 和粘膜免疫反应。

DESCRIPTION (Adapted from applicant's abstract): The oral cavity is a "portal of entry" for bacteria, fungi and other infectious agents that reach the respiratory and gastrointestinal tracts. Lining these tracts is the MALT, which can induce immunity or oral tolerance against bacteria species. The antigen-presenting cells known as DCs form a discrete microanatomical organization with T cells in MALT Peyer's patch, which is crucial for initiation and regulation of the immune response. Work from our laboratory and others have established the human oral mucosa as a rich repository of DCs. We presently understand little about the function and organization of DCs in these tissues. This R21 application proposes the hypothesis that, if proven, will support a new paradigm - that adaptive immunity is regulated at several levels by: (1) distinct DCs subsets that infiltrate the oral mucosa; (2) TLRs expressed; and (3) the antigens encountered. Our overall hypothesis is that the human oral mucosal DCs play pivotal roles in regulation of the adaptive immune response to specific antigens. The sub-hypotheses are: (1) distinct DC subsets infiltrate different microanatomical sites in the gingival/buccal mucosa; (2) these DC subsets are differentially responsive to LPS and other antigens by virtue of the expression of antigen-selective TLR2 and TLR4; and (3) the T cell response to antigens is regulated by DC responsiveness. The present application proposes the following aims: Aim 1: To characterize the DC subsets that infiltrate human oral mucosa in health and disease; and Aim 2: To determine the ability of DC subsets to regulate the T cell response to antigens in vitro. The PI has assembled a team of investigators with expertise in microbiology, oral pathology/stomatology, immuunohistochemistry, LPS purification/characterization, DC/Langerhans cell function and T cell function to carry out these studies. The investigators are all located on the Dallas campus of the Baylor Medical Center Hospital, including Baylor College of Dentistry-TAMUS and the Baylor Institute for Immunology Research. It is hoped this research will advance our understanding of how adaptive immunity to microbial antigens is initiated and regulated at the mucosal level. Our short-term objective is to acquire sufficient preliminary data/publications to facilitate the successful submission of an R01 proposal(s). Our long-term objective is to develop this research to the level of a program project on DCs and the mucosal immune response.