Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway.
Rheumatology (Oxford). 2010 Apr;49(4):632-9. doi: 10.1093/rheumatology/keq004. Epub 2010 Feb 9.
Autoimmunity has been a topic of intensive research for several decades, yet amazingly, no uniform hypothesis exists to explain the basis for the spectrum of autoantibody specificities seen in autoimmune diseases. It therefore seems appropriate to consider whether our current framework for understanding tolerance, and thus the mechanisms controlling the initiation and perpetuation of autoimmunity, may be faulty. Adapting the paradigm of Matzinger-the 'danger model', a case can be made for a perspective that appreciates the fundamental role of the tissues in controlling immune response, favouring a shift of focus in studies on the initiation of autoimmunity. Applying the elements of this model, I set forth a number of scenarios for how autoreactivity could emerge, with emphasis on the likely sources of the involved autoantigens and the functional basis of their appearance. The emerging picture is one in which disruption of tissue homeostasis takes centre stage, with the antigen-presenting cells as the key players.
自身免疫性疾病几十年来一直是一个研究热点，但令人惊讶的是，目前还没有一个统一的假说能够解释自身抗体特异性的范围。因此，我们似乎有必要考虑我们目前对免疫耐受的理解框架，以及控制自身免疫起始和持续的机制是否存在缺陷。借鉴马辛杰的范式——“危险模型”，我们可以提出一种观点，即认识到组织在控制免疫反应中的基本作用，从而在自身免疫起始的研究中转移关注焦点。应用该模型的要素，我提出了一些自身反应性出现的情况，重点是涉及的自身抗原的可能来源及其出现的功能基础。由此产生的画面是组织平衡紊乱占据中心舞台，抗原呈递细胞是关键角色。
