Maizels Rick
Institute of Immunology and Infection Research, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
Novartis Found Symp. 2007;281:192-204; discussion 204-9. doi: 10.1002/9780470062128.ch16.
Eukaryotic, multicellular parasites such as the helminth worms have a major impact on the mammalian immune system in two contexts. First, they have evolved sophisticated strategies for long-term immune evasion including recruiting natural suppressive mechanisms such as the regulatory T cell (Tregs). Tregs play a role not only in repressing immunity to parasites, but also in dampening bystander responses such as those to allergens. To achieve these effects, they produce a range of immunomodulators some of which are evolutionary homologues of immune system cytokines, while others are novel proteins capable of interfering with immune cell signalling and differentiation. The second context in which metazoa may have influenced their host is at the level of genetic polymorphism in immune response genes. Alleles at loci originally associated with predisposition to asthma have more recently been found to confer heightened resistance to helminth parasites. This may suggest a mechanistic link between more vigorous type 2 responses in both allergy and infection. On a broader perspective, one may speculate that alleles advantageous in the historical environment of prevalent infection, now display a deleterious phenotype in our more 'hygienic' societies.
真核多细胞寄生虫，如蠕虫，在两种情况下会对哺乳动物免疫系统产生重大影响。首先，它们进化出了复杂的长期免疫逃避策略，包括利用天然抑制机制，如调节性T细胞（Tregs）。Tregs不仅在抑制对寄生虫的免疫反应中发挥作用，还在抑制旁观者反应（如对过敏原的反应）中发挥作用。为了实现这些效果，它们会产生一系列免疫调节剂，其中一些是免疫系统细胞因子的进化同源物，而另一些则是能够干扰免疫细胞信号传导和分化的新型蛋白质。后生动物可能影响其宿主的第二种情况是在免疫反应基因的遗传多态性水平上。最初与哮喘易感性相关位点的等位基因，最近被发现能赋予对蠕虫寄生虫更强的抵抗力。这可能表明在过敏和感染中更强的2型反应之间存在机制联系。从更广泛的角度来看，人们可能推测，在普遍感染的历史环境中有利的等位基因，在我们现在更“卫生”的社会中表现出有害的表型。
