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Intraepithelial Lymphocytes All T cells - 85% CD8+ gd T cells may be frequent 70% in certain species or neonatal/germfree Express specific aEb7 integrin – ligand E cadherin on enterocytes Unresponsive to TcR stimulation Many extrathymically derived Intraepithelial Lymphocytes 5-10% CD4+ - ab TcR+ 85% CD8+ CD8ab+ ab TcR+ CD8aa+ ab TcR+ Some extrathymic gd TcR+ Extrathymic CD3+ IEL Proportions of subsets depends on age, environment etc Conventional T cells Primed in PP Cryptopatches DC TcR IL7R ckit Small lymphoid aggregates in small intestine of rodents and ? man CP Cryptopatches ~1000 in small intestine - ~1500 cells Contain DC, but no mature T or B cells Express receptors for haemopoietic cytokines, rag-1 and rag-2 Contain T cell precursors Extrathymic site of intestinal T cell development Regulation of Mucosal Immune Responses Harmless Antigen Food proteins, commensal bacteria Oral Tolerance Harmful Antigen Invasive bacteria, viruses, toxins Protective Immunity Regulation of Mucosal Immune Responses Most antigens entering mucosae are not pathogenic - foods, aerosols, commensals Protective immunity essential for life Harmless antigens induce tolerance Breakdown in tolerance ? disease IBD - bacteria Coeliac disease - gluten Asthma, hay fever - pollen etc Coeliac Disease Breakdown in oral tolerance to dietary gluten allows aberrant effector T cell responses which damage the intestine Villus atrophy + Crypt hyperplasia Normal Jejunum Coeliac Jejunum Intraepithelial Lymphocytes Intraepithelial Lymphocytes Intraepithelial Lymphocytes * Mucosal Immunity黏膜免疫 Innate responses critical 先天反应的关键 Specific immunity only invoked激活 if innate固有 response is overcome克服、攻下 特异性免疫只有先天免疫被攻克的情况下才被激活 Humoral体液 Cell mediated细胞介导 Functions of Mucus粘液的功能 屏障 多孔质凝胶 陷阱 粘稠液体凝胶 结合 溶胶 Innate Defence at Mucosal Surfaces粘膜表面的固有免疫 Mechanical - Epithelial barrier trefoils + Mucus Coughing, sneezing, vomiting, Cilia, peristalsis Humoral
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