哮喘发病过程中天然免疫和获得性免疫的相互影响:来自哮喘急性加重研究的新视角
2010/07/05
哮喘是一种复杂的多基因疾病,最常见的哮喘是过敏性哮喘,在儿童或青少年中患病率最高,这也是本综述的主要着眼点。过敏性哮喘的主要危险因素是长期吸入过敏原的刺激,由于不能产生保护性免疫耐受而致敏。这种耐受过程由气道粘膜树突细胞完成,正常情况下能致使调节性T淋巴细胞活化,从而抑制TH2记忆细胞的激活,导致IgE产生以及促进效应细胞通过IgE介导的组织损伤。越来越多的证据表明了该过程的复杂性,特别是天然免疫机制和获得性免疫机制之间存在重叠,这些机制中常常是一个细胞器产生的每一信号都会使另一部分产生应答。使这一过程更为复杂的是,局部的间质也能发出信号参与这一免疫应答过程,以尽量满足局部微环境需要。这种天然免疫和获得性免疫途径之间的平衡紊乱是很多疾病发生的基础,对于过敏性哮喘来说,病毒感染触发的哮喘加重就是一个很好的例子。
(苏楠 审校)
Holt PG, et al. J Allergy Clin Immunol. 2010 Apr 13. [Epub ahead of print]
Interactions between innate and adaptive immunity in asthma pathogenesis: New perspectives from studies on acute exacerbations.
Holt PG, Strickland DH.
Telethon Institute for Child Health Research and the Centre for Child Health Research, Faculty of Medicine and Dentistry, the University of Western Australia, Perth, Australia.
Abstract
Asthma is a complex multigenic disease. The most frequently encountered form is atopic asthma, which is at its highest prevalence during childhood/young adulthood, and this represents the main focus of this review. The primary risk factor for atopic asthma is sensitization to perennial aeroallergens resulting from a failure to generate protective immunologic tolerance. This tolerance process is orchestrated by airway mucosal dendritic cells and normally results in programming of regulatory T cells, which inhibit activation of the T(H)2 memory cells that, among other activities, drive IgE production and prime the effector populations responsible for IgE-mediated tissue damage. Emerging evidence highlights the complexity of this process, in particular the iterative nature of the underlying interactions between innate and adaptive immune mechanisms in which virtually every signal emanating from one cellular compartment provokes an answering response from the other. To further complicate this picture, the local mesenchyme can also interpose signals to fine tune immune responses to optimally meet local microenvironmental needs. Perturbation of the balance between these interlinked innate and adaptive immune pathways is increasingly believed to be the basis for disease expression, and in the specific case of atopic asthma, the prototypic example of this (discussed below) is acute exacerbations triggered by viral infections.
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过敏性哮喘患者的气道IL-6水平独立于炎症,但与气道功能下降相关
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哮喘或慢性阻塞性肺疾病导致固定性气流阻塞:5年的随访研究