Christen Urs, Hintermann Edith
Pharmazentrum Frankfurt / Zentrum für Arzneimittelforschung, Entwicklung und Sicherheit (ZAFES), Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Int J Biomed Sci. 2007 Jun;3(2):86-92.
One possible way of how autoimmune disease can be initiated is by infection with a foreign pathogen. Especially viruses are thought to act as triggering factors, inducing a detrimental attack against 'self' by the immune system of a susceptible host because of two major reasons. First, viruses cause a massive inflammation of the infected tissue and therefore initiate the infiltration of a broad variety of leukocytes, including potentially 'self'-reactive lymphocytes. Second, some viruses have been demonstrated to bear molecules with a strong structural similarity to host components. The existence of such a 'molecular mimicry' may elicit an immune response, which is initially generated in defense against the invading pathogen but in a second wave targets similar structures of the host. In the present review we will reflect on the dual role of inflammatory factors during this process and discuss possibilities of how such a detrimental second wave of the immune system can be blocked. Most of the presented data have been obtained from animal models that integrate the concept of molecular mimicry. They use transgenic mice expressing a defined model protein specifically in a target tissue and a virus containing either an identical or a similar protein as a triggering factor.
自身免疫性疾病可能的引发方式之一是感染外来病原体。尤其是病毒被认为是触发因素，由于两个主要原因，它会诱导易感宿主的免疫系统对“自身”发动有害攻击。首先，病毒会导致受感染组织发生大规模炎症，从而引发多种白细胞的浸润，包括潜在的“自身”反应性淋巴细胞。其次，一些病毒已被证明带有与宿主成分结构高度相似的分子。这种“分子模拟”的存在可能引发免疫反应，该反应最初是为抵御入侵病原体而产生，但在第二波中会针对宿主的相似结构。在本综述中，我们将思考炎症因子在此过程中的双重作用，并讨论如何阻断免疫系统这种有害的第二波攻击的可能性。所呈现的大多数数据都来自整合了分子模拟概念的动物模型。它们使用在特定靶组织中特异性表达特定模型蛋白的转基因小鼠，以及含有相同或相似蛋白作为触发因素的病毒。
