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感染后的表观遗传免疫修饰——一柄双刃剑
Postinfectious Epigenetic Immune Modifications — A Double-Edged Sword


Andrew R. DiNardo ... 其他 • 2021.01.21

抗原特异性致敏淋巴细胞,进而诱导产生免疫的机制已为我们所充分了解。在过去10年间,单核细胞、自然杀伤细胞和树突状细胞发生特异性致敏的重要性逐渐为我们所认识。上述致敏作用是由持久表观遗传变化所引起,这些变化可显著增强或抑制免疫应答。简而言之,免疫刺激(感染或免疫)可对宿主的免疫应答产生长期影响。本文将介绍这些表观遗传效应的产生机制,以及它们如何影响人体对后续感染和疫苗接种产生的应答。表观遗传疗法已改善了癌症患者的临床结局,并即将在临床上常规应用于感染治疗和疫苗接种。

 

体液免疫和细胞介导免疫的特异性


19世纪90年代,Klemperer兄弟证明,给家兔接种灭活肺炎球菌可在肺炎球菌攻击时产生保护作用。将免疫家兔血清输入非免疫家兔体内可传递上述保护作用,这体现了体液免疫的概念。他们进一步发现,上述接种不能在其他肺炎球菌菌株攻击时产生保护作用,因而表明体液免疫是一种免疫特异性现象1

细胞介导免疫的概念发展得较慢。科赫试图使用结核菌素(从结核分枝杆菌中提取的一组蛋白质)建立对结核病的免疫,但没有成功。Von Pirquet表明,给结核病患者注射结核菌素可引起局部炎症反应;上述迟发型超敏反应的特征是淋巴细胞和巨噬细胞聚集,并具有抗原特异性。1957年,Dubos和Schaedler报道,给小鼠注射卡介苗(BCG)(牛分枝杆菌减毒株)可增强其对金黄色葡萄球菌和偶然分枝杆菌的抵抗力2。他们将上述非抗原特异性免疫归因于单核细胞的激活,这一现象已在体外试验中得到证实3,4。Mackaness 5,6的开创性试验表明,用布鲁菌等胞内微生物或卡介苗感染小鼠可保护其免受抗原方面无关的细菌(如李斯特菌)感染。他们提出的机制是抗原特异性刺激增强了巨噬细胞的非特异性杀菌能力。





作者信息

Andrew R. DiNardo, M.D., Mihai G. Netea, M.D., Ph.D., and Daniel M. Musher, M.D.
From the Global Tuberculosis Program, William T. Shearer Center for Human Immunobiology, Texas Children’s Hospital (A.R.D.), the Immigrant and Global Health Program, Department of Pediatrics (A.R.D.), and the Departments of Medicine and Molecular Virology and Microbiology (D.M.M.), Baylor College of Medicine, and the Medical Care Line, Infectious Disease Section, Michael E. DeBakey Veterans Affairs Medical Center (D.M.M.) — all in Houston; the Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands (M.G.N.); and the Department of Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany (M.G.N.). Address reprint requests to Dr. DiNardo at dinardo@bcm.edu.

 

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