医学免疫学课件：抗体对肠道菌群组成的影响

1、抗体对肠道菌群组成的影响01肠道菌群02肠道抗体03抗体影响菌群组成04抗体促进健康05前景展望06参考文献01肠道菌群Figure: Bumler, A. et al, Nature 2016; 535(7610): 85-93.01肠道菌群肠道菌群丰富的微生物影响因素多样正常菌群的重要性失衡导致疾病02肠道抗体Figure: Murphy, K., Travers, Paul, Walport, Mark, & Janeway, Charles, Janeways immunobiology (8th ed.) 2012: Figure 10.2402肠道抗体肠道抗体控制微生物主要是IgA

2、，34g/DIgM, IgGFigure: Murphy, K., Travers, Paul, Walport, Mark, & Janeway, Charles, Janeways immunobiology (8th ed.) 2012: Figure 10.2202肠道抗体IgA作用方式分泌到肠腔温和中和作用结合微生物与毒素Figure: Bunker, J. et al, Immunity 2015; 43(3): 541-553 02肠道抗体IgA个体特异性结合大量菌群人45%小肠大肠Figure: Bunker, J. et al, Immunity 2015; 43(3): 5

3、41-553 02肠道抗体IgA结合的菌群与宿主组织联系更紧密与炎症和疾病相关 黏液环境免疫反应03抗体影响菌群组成03抗体影响菌群组成基因缺陷模型免疫过程重要的酶缺陷免疫功能缺陷构建模型Figure: Zhang, H. et al, International Society for Microbial Ecology 2015; 9: Figure 4A 4E 03抗体影响菌群组成适应性免疫缺陷改变菌群组成重组活化基因RAGT细胞和B细胞功能缺损Akkermansia muciniphila黏膜相关微生物Figure: Kawamoto, S. et al, Immunity 2014;

4、 41: Figure S103抗体影响菌群组成适应性免疫缺陷改变菌群组成重组活化基因RAGT细胞和B细胞功能缺损黏膜相关微生物菌群多样性Figure: Fagarasan, S. et al, Science 2002; 298: Figure 3A 03抗体影响菌群组成抗体缺陷改变菌群组成活化诱导胞嘧啶核苷脱氨酶AID 缺乏IgARag2/ 骨髓移植IGHMIGHAPIgRFigure: Suzuki, K. et al, Proc. Natl Acad. Sci. USA 2004; 101: Figure 3B 03抗体影响菌群组成抗体缺陷改变菌群组成活化诱导胞嘧啶核苷脱氨酶AIDRa

5、g2/ 骨髓移植 - 恢复AIDIGHMIGHAPIgRFigure: Kawamoto, S. et al, Immunity 2014; 41: Figure S1 03抗体影响菌群组成抗体缺陷改变菌群组成活化诱导胞嘧啶核苷脱氨酶AIDRag2/ 骨髓移植IGHM 缺少B细胞IGHAPIgRFigure: Mirpuri, J. et al, Gut Microbes 2014; 5: Figure 4A 03抗体影响菌群组成抗体缺陷改变菌群组成IGHM活化诱导胞嘧啶核苷脱氨酶AIDRag2/ 骨髓移植IGHA 缺乏IgAPIgRFigure: Reikvam, D. H. et al,

6、Eur. J. Immunol 2012; 42: Table 5 03抗体影响菌群组成抗体缺陷改变菌群组成IGHM活化诱导胞嘧啶核苷脱氨酶AIDRag2/ 骨髓移植IGHAPIgR 缺少黏膜分泌抗体Figure: Kubinak, Round, Nature Reviews Immunology 2016; 16: Figure 1 03抗体影响菌群组成T细胞影响IgA作用抗体应答的方式胸腺非依赖性胸腺依赖性阻止黏膜入侵04抗体促进健康Figure: Wei, M. et al, Nat. Immunol 2011; 12: Figure 6A04抗体促进健康抵抗细菌入侵AID缺陷小肠结肠炎

7、耶尔森菌模型PIgR 缺少黏膜分泌抗体胸腺依赖性IgA缺陷04抗体促进健康调节毒力因子中和作用下调促炎表位限制黏附因子间接抵抗细菌入侵Figure: Murphy, K., Travers, Paul, Walport, Mark, & Janeway, Charles, Janeways immunobiology (8th ed.) 2012: Figure 10.2205前景展望Figure: Kubinak, Round, Nature Reviews Immunology 2016; 16: Figure 3 05前景展望利用抗体改善菌群05前景展望探索细菌功能抗原选择机制改善菌群诊

8、断疾病促进健康应用06参考文献06参考文献Andreas J. Bumler, & Vanessa Sperandio. Interactions between the microbiota and pathogenic bacteria in the gut. Nature, 535(7610), 85 (2016).Murphy, K., Travers, Paul, Walport, Mark, & Janeway, Charles. Janeways immunobiology (8th ed.). New York: Garland Science (2012).Bunker, J

9、. J. et al. Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A. Immunity 43, 541553 (2015).Zhang, H., Sparks, J. B., Karyala, S. V., Settlage, R. & Luo, X. M. Host adaptive immunity alters gut microbiota. ISME J. 9, 770781 (2015).Kawamoto, S. et al. Foxp3+ T

10、 cells regulate immunoglobulin a selection and facilitate diversification of bacterial species responsible for immune homeostasis. Immunity 41, 152165 (2014). Fagarasan, S. et al. Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora. Science 298, 14241427 (2002).06

11、参考文献Suzuki, K. et al. Aberrant expansion of segmented filamentous bacteria in IgA-deficient gut. Proc. Natl Acad. Sci. USA 101, 19811986 (2004).Wei, M. et al. Mice carrying a knock-in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nat. Immunol. 12, 264270 (2011).Mirpuri, J. et al. Proteobacteria-specific IgA regulates maturation of the intestinal microbiota. Gut Microbes 5, 2839 (2014).Reikvam, D. H. et al. Epithelial-microbial crosstalk in polymeric Ig receptor deficient mice