DENDRITIC CELLS, LPS AND ORAL MUCOSA

描述（改编自申请人摘要）：口腔是一个“门户” 细菌、真菌和其他传染性病原体， 呼吸道和胃肠道。 排列在这些小块上的是麦芽， 其可以诱导针对细菌物种的免疫或口服耐受。 的 称为DC的抗原呈递细胞形成离散的微解剖结构， 组织与MALT派尔集合淋巴结中的T细胞，这对于 启动和调节免疫反应。 我们实验室的工作 等人已经将人类口腔粘膜建立为丰富的DC储存库。 目前，我们对区议会的职能和组织结构知之甚少， 这些组织。 这个R21应用程序提出了一个假设，如果得到证实， 将支持一种新的范式--适应性免疫是在几个不同的阶段进行调节的。 通过：（1）浸润口腔粘膜的不同DC亚群;（2）TLR 表达;（3）遇到的抗原。 我们的总体假设是 人口腔黏膜DCs在适应性免疫调节中起关键作用， 对特定抗原的免疫反应。 这些子假设是：（1）不同的 DC亚群浸润牙龈/颊的不同显微解剖部位 （2）这些DC亚群对LPS和其他免疫反应有不同的反应。 - 通过抗原选择性TLR 2和TLR 4的表达来表达抗原;和 (3)T细胞对抗原的应答受DC应答调节。 的 本申请提出了以下目的：目的1：表征DC 目的2：在健康和疾病中浸润人口腔粘膜的亚群; 确定DC亚群调节T细胞应答的能力 体外抗原。 PI已经组建了一个调查小组， 具有微生物学、口腔病理学/口腔学、免疫组织化学 LPS纯化/表征、DC/朗格汉斯细胞功能和T细胞 发挥作用，开展这些研究。 调查人员都位于 贝勒医学中心医院的达拉斯校区，包括贝勒学院 和贝勒免疫学研究所。 是 我希望这项研究将促进我们对适应性免疫如何 微生物抗原在粘膜水平被启动和调节。 我们 短期目标是获得足够初步数据/出版物， 促进R 01提案的成功提交。 我们的长期 我们的目标是将这项研究发展到有关发展中国家的计划项目的水平 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.