Bailey Mick, Haverson Karin
School of Clinical Veterinary Science, University of Bristol, Langford House, Langford, Bristol BS40 5DU, United Kingdom.
Vet Res. 2006 May-Jun;37(3):443-53. doi: 10.1051/vetres:2006013. Epub 2006 Apr 14.
The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting appropriate effector or regulatory responses. Since the immune system is likely to have evolved initially in mucosal tissues, the requirement to prevent damaging allergic responses must be at least as old as the adaptive immune system, and studies of the mechanisms should include a range of non-mammalian species. Despite the importance for rational design of vaccines and for control of allergic reactions, the mechanisms involved are still largely unclear. It is not clear that the classical experimental protocol of "oral tolerance" is, in fact, measuring a biologically important phenomenon, nor is it clear whether tolerance is regulated in the evolutionarily recent organised lymphoid tissue (the lymph nodes) or the more ancient, diffuse architecture in the intestine. The capacity of the immune system to discriminate between "dangerous" and "harmless" antigens appears to develop with age and exposure to microbial flora. Thus, the ability of an individual or a group of animals to correctly regulate mucosal immune responses will depend on age, genetics and on their microbial environment and history. Attempts to manipulate the mucosal immune system towards active immune responses by oral vaccines, or towards oral tolerance, are likely to be confounded by environmentally-induced variability between individuals and between groups of animals.
黏膜免疫系统会接触到一系列与病原体相关的抗原，对此它必须产生积极的免疫反应。然而，它也会接触到大量与食物和共生微生物群相关的无害抗原，对这些抗原产生积极的、炎症性免疫反应是不可取的。黏膜免疫系统必须具备能够评估其所接触抗原并产生适当效应或调节反应的机制。由于免疫系统最初可能是在黏膜组织中进化而来的，预防有害过敏反应的需求至少与适应性免疫系统一样古老，对相关机制的研究应涵盖一系列非哺乳动物物种。尽管对于合理设计疫苗和控制过敏反应很重要，但其中涉及的机制仍大多不清楚。目前尚不清楚经典的“口服耐受”实验方案实际上是否在测量一种生物学上重要的现象，也不清楚耐受是在进化上较新的有组织淋巴组织（淋巴结）中调节，还是在肠道中更古老的弥散结构中调节。免疫系统区分“危险”和“无害”抗原的能力似乎会随着年龄增长以及接触微生物群而发展。因此，个体或一组动物正确调节黏膜免疫反应的能力将取决于年龄、遗传因素以及它们的微生物环境和经历。通过口服疫苗使黏膜免疫系统产生积极免疫反应或诱导口服耐受的尝试，很可能会因个体之间以及动物群体之间由环境引起的变异性而受到干扰。
