THE INTESTINAL IMMUNE-SYSTEM
THE INTESTINAL IMMUNE-SYSTEM
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DOI：
10.1136/gut.30.12.1679
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发表时间：
1989-12-01
期刊：
影响因子：
24.5
通讯作者：
DOE, WF
中科院分区：
文献类型：
--
作者：
DOE, WF
局部肠道免疫的概念起源于贝斯雷德卡的观察，他观察到，无论血清抗体的滴度如何，口服沙门氏菌免疫都能提供坚实的保护，防止痢疾感染。但临床上的好处是可变的，持续时间很短，而且人们对此失去了兴趣。直到赫里曼斯发现了IgA，以及含有IgA的浆细胞在正常肠粘膜中明显占优势，才有了进一步的进展。2血清和分泌型IgA的抗原决定簇之间的差异导致了对粘膜表面IgA抗体的分泌和功能至关重要的另一个多肽链--分泌型成分(SC)的识别。克里斯·布斯很快认识到粘膜免疫系统在肠道疾病发病机制中的重要性。1969年，当我作为Hammersmith的室友来到这里时，已经发表了几项针对乳糜泻的开创性免疫学研究。Hammersmith的临床研究精神不仅通过应用基本的科学知识和技术刺激了对人类疾病的研究，还通过认识到对人类疾病的仔细研究也可以提供机会来增进我们对人类生物学的理解。我还记得1969年的一家门诊诊所，当时克里斯递给我一封推荐信，上面写着一位他从未见过的新病人：“听起来像阿尔法链疾病，很有意思。”几个月后，赫曼斯来到哈默史密斯大学，发表了一系列关于分泌型免疫系统的精彩演讲。那一周的重要会议包括介绍后来最早公布的阿尔法链疾病病例之一。4在这些早期发现以来的几十年里，在了解肠道免疫反应的生理学方面取得的重大进展以及分子生物学的出现，有助于阐明粘膜表面分泌抗体和细胞反应的诱导和调节。
The concept of localised intestinal immunity has its origins in Besredka's observation that oral immunisation using killed salmonella organisms provided solid protection against dysenteric infection irrespective of the titres of serum antibody.'But the clinical benefits were variable and short lived and interest lapsed. Little further progress was made until Heremans' discovery of IgA and the marked predominance of IgA-containing plasma cellsin normal intestinal mucosa. 2 The differences between the antigenic determinants of serum and secretory IgA led to the identification of an additional polypeptide chain, the secretory component (SC), which is essential to the secretion and function of IgA antibody at mucosal surfaces.'The importance of the mucosal immune system to the pathogenesis of intestinal disease was swiftly recognised by Chris Booth. When I arrived as a houseman at Hammersmith in 1969, several pioneering immunological studies of coeliac disease had been published. The clinical research ethos at Hammersmith stimulated the study of human disease not only by applying basic scientific knowledge and techniques but also by recognising that careful study of human disease can also provide opportunities for advancing our understanding of human biology. I recall the outpatient clinic in 1969 when Chris handed me the referral letter for a new patient he had not seen:'Fascinating, sounds like alpha chain disease.'Several months later Heremans came to Hammersmith to deliver a series of outstanding lectures on the secretory immune system. Grand rounds that week included the presentation of what was to be one of the earliest published cases of alpha chain disease. 4 In the decades since these earlydiscoveries, major advances in understanding the physiology of the intestinal immune response and the advent of molecular biology have helped to elucidate the induction and regulation of the secretory antibody and cellular responses at mucosal surfaces.