Wallis Russell
Departments of Infection, Immunity and Inflammation and Biochemistry, University of Leicester, Leicester, UK.
Immunobiology. 2007;212(4-5):289-99. doi: 10.1016/j.imbio.2006.11.004. Epub 2006 Dec 18.
The lectin pathway of complement performs a key role within the immune system by recognising pathogens through patterns of sugar moieties displayed on their cell surfaces and neutralising them via an antibody-independent reaction cascade. While particularly important during early childhood before the adaptive immune system is established, or when adaptive immunity is compromised, it has a protective function throughout life, neutralising invading pathogens directly and helping to stimulate and direct an effective immune response. Complement activation is initiated when complexes comprising mannose-binding lectin (MBL) or serum ficolins and MBL-associated serine protease-2 (MASP-2) bind to pathogens. Binding induces conformational changes in these complexes, leading to autoactivation of the MASPs, which in turn activate the downstream reaction cascade. A major goal in complement research is to understand the molecular events that trigger complement activation. Over the last few years, structure-function studies have improved our knowledge of the way in which MBL binds to MASPs by defining the portions of these proteins that interact and by solving the structures of key protein fragments. In this review, I will summarise the main findings of these studies and describe current theories to explain how the components combine to initiate the reaction cascade.
补体的凝集素途径在免疫系统中发挥关键作用，它通过识别病原体细胞表面展示的糖基模式，并通过抗体非依赖的反应级联来中和病原体。虽然在适应性免疫系统建立之前的幼儿期，或者在适应性免疫受损时，它尤为重要，但它在整个生命过程中都具有保护功能，可直接中和入侵的病原体，并有助于刺激和引导有效的免疫反应。当包含甘露糖结合凝集素（MBL）或血清纤维胶凝蛋白以及MBL相关丝氨酸蛋白酶-2（MASP-2）的复合物与病原体结合时，补体激活开始。结合会诱导这些复合物发生构象变化，导致MASP的自身激活，进而激活下游反应级联。补体研究的一个主要目标是了解触发补体激活的分子事件。在过去几年中，结构-功能研究通过确定这些蛋白质相互作用的部分并解析关键蛋白质片段的结构，提高了我们对MBL与MASP结合方式的确切了解。在这篇综述中，我将总结这些研究的主要发现，并描述当前的理论，以解释这些成分如何结合启动反应级联。
