Renz Harald, Blümer Nicole, Virna Simona, Sel Serdar, Garn Holger
Department of Clinical Chemistry and Molecular Diagnostics, Philipps-University Marburg, Germany.
Chem Immunol Allergy. 2006;91:30-48. doi: 10.1159/000090228.
The dramatic increase of allergic disorders in the last decades made their study an imperious demand. The increasing incidence of the development of allergic disorders seems to be associated with the modern westernized lifestyle, but causal reasons and the underlying mechanisms are far from being completely understood. Evidences suggest that priming of the immune responses against allergens happens already in utero. In addition, early life events are essential in shaping the immune answer towards the Th1- or Th2-profile, associated with a nonallergic or allergic phenotype, respectively. The hygiene hypothesis suggests that an early life environment rich in normal microbial flora primes the immune system in the Th1 direction towards clinical balance while a 'sterile' environment rather promotes the development of pathological immune phenotypes. In this review we collect epidemiological evidence for this concept. The data suggest an association between environment, lifestyle and the development of allergic diseases. This is the basis for the development of new hypotheses regarding the underlying pathomechanisms. The current view of cellular and molecular mechanisms underlying these phenomena includes fine-balancing between innate immune mechanisms and Th1, Th2 and regulatory T cells. These novel immunoregulatory events may explain the hygiene hypothesis by an interaction of environmental factors with innate immune mechanisms and various subtypes of T-cell responses.
在过去几十年中，过敏性疾病急剧增加，这使得对其进行研究成为一项迫切需求。过敏性疾病发病率的不断上升似乎与现代西方化生活方式有关，但其因果关系及潜在机制远未完全明晰。有证据表明，针对过敏原的免疫反应致敏在子宫内就已发生。此外，早期生活事件对于塑造免疫反应向Th1或Th2型分化至关重要，这分别与非过敏性或过敏性表型相关。卫生假说认为，富含正常微生物菌群的早期生活环境会使免疫系统向Th1方向致敏，从而实现临床平衡，而“无菌”环境则更易促进病理性免疫表型的发展。在本综述中，我们收集了支持这一概念的流行病学证据。数据表明环境、生活方式与过敏性疾病的发生之间存在关联。这为关于潜在发病机制的新假说的提出奠定了基础。目前对这些现象背后细胞和分子机制的看法包括先天免疫机制与Th1、Th2及调节性T细胞之间的精细平衡。这些新的免疫调节事件或许可以通过环境因素与先天免疫机制及各种T细胞反应亚型的相互作用来解释卫生假说。
