9.黏膜免疫硕士研究生.pptVIP

Shigella flexneri, a cause of bacterial dysentery, infects intestinal epithelial cells, triggering activation of the NF?B pathway. Shigella flexneri binds to M cells and is translocated beneath the gut epithelium (first panel). The bacteria infect intestinal epithelial cells from their basal surface and are released into the cytoplasm (second panel). Muramyl tripeptides containing diaminopimelic acid in the cell walls of the shigellae bind to and oligomerize the protein NOD1. Oligomerized NOD1 binds the serine/ threonine kinase RIPK2, which triggers activation of the NF?B pathway , leading to the transcription of genes for chemokines and cytokines (third panel). Activated epithelial cells release the chemokine CXCL8, which acts as a neutrophil chemoattractant (fourth panel). I?B, inhibitor of NF?B; I?K, I?B kinase. 针对共生菌的免疫应答与肠道疾病 Mucosal dendritic cells regulate the induction of tolerance and immunity in the intestine. Under normal conditions (left panels), dendritic cells are present in the mucosa underlying the epithelium and can acquire antigens from foods or commensal organisms. They take these antigens to the draining mesenteric lymph node, where they present them to naive CD4 T cells. There is, however, constitutive production by epithelial cells and mesenchymal cells of molecules such as TGF-?, thymic stromal lymphopoietin (TSLP), and prostaglandin E2 (PGE2), which maintain the local dendritic cells in a quiescent state with low levels of co-stimulatory molecules, so that when they present antigen to naive CD4 T cells, anti-inflammatory or regulatory T cells are generated. These recirculate back to the intestinal wall and maintain tolerance to the harmless antigens. Invasion by pathogens or a massive influx of commensal bacteria (right panels) overcomes these homeostatic mechanisms, resulting in full activation of local dendritic cells and their expression of co-stimulatory molecules and pro-inflammatory cytokines such as I L -12. Presentation of antigen to