Department of Pathology, University of Michigan Medical School Ann Arbor, MI, USA ; Section of Pathology and Laboratory Medicine, Veterans Affairs Ann Arbor Healthcare System Ann Arbor, MI, USA.
Front Immunol. 2013 Feb 25;4:43. doi: 10.3389/fimmu.2013.00043. eCollection 2013.
Granulomas are cellular inflammations that vary widely in histologic appearance depending upon the inciting agent and immunologic status of the responding host. Despite their heterogeneity, granulomas are at their core an ancient innate sequestration response characterized by the accumulation of mononuclear phagocytes. In fact, this innate cellular response was first observed by Metchnikov in simple invertebrates. Among higher vertebrates, environmental pressures have resulted in the evolution of more sophisticated adaptive immune responses which can be superimposed upon and modify the character of granulomatous inflammation. Compared to immune responses that rapidly neutralize and eliminate infectious agents, the granuloma represents a less desirable "fall back" response which still has value to the host but can be co-opted by certain infectious agents and contribute to bystander organ damage. Understanding granulomas requires an analysis of the complex interplay of innate and adaptive molecular signals that govern the focal accumulation and activity of their cellular components. Among these signals, small molecular weight chemoattractant proteins known as chemokines are potentially important contributors as they participate in both directing leukocyte migration and function. This tract will discuss the contribution of chemokines to the development of innate and adaptive granuloma formation, as well as describe their relationship to more recently evolved cytokines generated during adaptive immune responses.
肉芽肿是一种细胞炎症，其组织学表现差异很大，取决于刺激物和反应宿主的免疫状态。尽管它们具有异质性，但肉芽肿本质上是一种古老的固有隔离反应，其特征是单核吞噬细胞的积累。事实上，这种固有细胞反应首先是由梅契尼科夫在简单的无脊椎动物中观察到的。在高等脊椎动物中，环境压力导致了更复杂的适应性免疫反应的进化，这些反应可以叠加并改变肉芽肿炎症的特征。与迅速中和和消除感染因子的免疫反应相比，肉芽肿代表了一种不太理想的“后备”反应，它对宿主仍然有价值，但可能被某些感染因子利用，并导致旁观者器官损伤。了解肉芽肿需要分析固有和适应性分子信号的复杂相互作用，这些信号控制着其细胞成分的局灶性聚集和活性。在这些信号中，被称为趋化因子的小分子化学引诱蛋白可能是重要的贡献者，因为它们参与了白细胞的迁移和功能。本专题将讨论趋化因子对固有和适应性肉芽肿形成的贡献，并描述它们与适应性免疫反应期间产生的最近进化的细胞因子的关系。
