DO GUT BACTERIA PROVOKE INFLAMMATORY BOWEL DISEASE?

描述 两个研究小组[约翰·塞布拉博士，生物学教授，大学 宾夕法尼亚州，费城，和海伦娜Tlaskalova博士等。例如，研究所 捷克共和国布拉格微生物学中心]， 奖[FIRCA]，计划分析一些小鼠模型，用于人类 炎症性肠病[IBD]。 他们的目的是评估是否以及 肠道细菌或食物抗原[Ags]可能会引起或加剧 炎症性肠病变通过刺激一个或多个元素的 粘膜免疫系统 他们将进一步研究 可导致针对“正常”肠抗原的正常肠粘膜应答 从整体免疫系统的失调，以及它是否会导致 弗兰克自身免疫 宾夕法尼亚州的小组一直在澄清细节 正常的体液和细胞粘膜免疫反应 肠道细菌-这些反应如何导致“正常”的发展 肠道系统的生理状态，通常是自限性的。 的 Czeck小组一直在评估口服麦胶蛋白（小麦蛋白） 可以在许多小鼠模型中诱导肠道病变-显然是由于 “正常”免疫反应失调。 捷克集团已 无菌[GF] IL-2（-/-）小鼠和GF 严重联合免疫缺陷小鼠。 这些和无胸腺（nu/nu） IBD的鼠模型将用于测试正常组织的作用， 细菌、条件致病菌和食物抗原作为 肠道病变，使用细胞和分子技术。 养父 粘膜细胞成分的子集的转移将用于揭示 免疫抑制剂或调节剂的作用和可能的抗原特异性 肠道疾病中的细胞。 免疫组织化学分析将 用于确定原位致病过程中涉及的元素。 在 粘膜系统成分的体外测定：派伊尔集合淋巴结[PP]或 上皮内固有层[LP] B细胞、NK和CD 8 + T细胞 白细胞[IEL]空间和派伊尔结和固有层中的CD 4 + T细胞 也将使用对肠道微生物和食物抗原具有反应性的。 克 阴性[E. Coli，M. morganii、拟杆菌、S. Typhimurium-无毒的]， 革兰氏阳性菌[G]、肠球菌、L.单基因无毒， 分段丝状细菌]，小麦麦醇溶蛋白将被测试为 可能是假的

DESCRIPTION The two research groups [Dr. John Cebra, Professor of Biology, University of Pennsylvania, Philadelphia, and Dr. Helena Tlaskalova et. al., Institute of Microbiology, Prague, Czech Republic], under the auspices of the Fogarty Award [FIRCA], plan to analyze a number of murine models for human inflammatory bowel disease [IBD]. Their aim is to assess whether and which gut bacteria or food antigens [Ags] may act to provoke or exacerbate inflammatory bowel lesions by stimulating one or more elements of the mucosal immune system. They will further examine how deviation of the normal gut mucosal response against "normal" intestinal antigens may result from dysregulation of the overall immune system and whether it can lead to frank autoimmunity. The Pennsylvania group has been elucidating the details of the 'normal' humoral and cellular mucosal immune responses to commensal gut bacteria --how these responses lead to the development of the 'normal' physiologic state of the gut system and are normally self-limiting. The Czeck group has been assessing how oral feeding with gliadin [wheat protein] can induce intestinal lesions in a number of murine models -- apparently due to dysregulation of the 'normal' immune response. The Czech group has established colonies of germ free [GF] IL-2 (-/-) mice and GF severe-combined-immunodeficient [SCID] mice. These, and athymic (nu/nu) murine models for IBD will be used to test the role(s) of normal commensal bacteria, opportunistic pathogens, and food antigens as provocateurs of intestinal bowel lesions, using cellular and molecular techniques. Adoptive transfers of sub-sets of mucosal cellular elements will be used to reveal the role(s) and possible antigen specificities of provocateurs or regulatory cells in Intestinal Bowel Disease. Immunohistochemical analyses will be used to identify the elements involved in pathogenic processes in situ. In vitro assays of elements of the mucosal system: Peyer's patch [PP] or lamina propria [LP] B cells, NK and CD8+ T cells in the intra epithelial leukocyte [IEL] space, and CD4+ T cells in peyer's patch and lamina propria reactive against gut microbial and foods antigens will also be used. Gram negative [E. Coli, M. morganii, bacteroides, S. Typhimurium-avirulent], Gram positive [lactobacillus, enterococcus, L. monoctogenes-avirulent, segmented filamentous bacteria], and wheat gliadin will be tested as possible provocateurs.