Thiel Steffen, Gadjeva Mihaela
Department of Medical Microbiology and Immunology, University of Aarhus, Aarhus, Denmark.
Adv Exp Med Biol. 2009;653:58-73. doi: 10.1007/978-1-4419-0901-5_5.
Innate immunity comprises a sophisticated network of molecules, which recognize pathogens, and effector molecules, working together to establish a quick and efficient immune response to infectious agents. Complement activation triggered by mannan binding lectin (MBL) or ficolins represents a beautiful example of this network Both MBL and ficolins recognize specific chemical structures on the surface of antigens and pathogens, thus bind to a broad variety of pathogens. Once bound further complement deposition is achieved through a cascade of proteolytic reactions. MBL and ficolin induced complement activation is critical for adequate anti-bacterial, anti-fungal and anti-viral responses. This is well illustrated by numerous and convincing studies that demonstrate associations between MBL deficiency and infections. Recent work has also highlighted that MBL and ficolins recognize self-structures, thus extending the role of these molecules beyond the traditional view of first line defense molecules. It appears that MBL deficiency may modulate the prognosis of inflammatory and autoimmune diseases. What is known about the mechanisms behind this broad scope of activities of MBL and ficolins is discussed in this chapter.
固有免疫由一个复杂的分子网络组成,这些分子可识别病原体,还有效应分子,它们共同作用以建立对感染因子的快速有效免疫反应。由甘露糖结合凝集素(MBL)或纤维胶凝蛋白触发的补体激活代表了这个网络的一个很好的例子。MBL和纤维胶凝蛋白都能识别抗原和病原体表面的特定化学结构,因此能与多种病原体结合。一旦结合,通过一系列蛋白水解反应可实现进一步的补体沉积。MBL和纤维胶凝蛋白诱导的补体激活对于充分的抗菌、抗真菌和抗病毒反应至关重要。大量有说服力的研究表明MBL缺陷与感染之间存在关联,很好地说明了这一点。最近的研究还强调,MBL和纤维胶凝蛋白能识别自身结构,从而将这些分子的作用扩展到了一线防御分子的传统观点之外。MBL缺陷似乎可能会调节炎症和自身免疫性疾病的预后。本章将讨论关于MBL和纤维胶凝蛋白这种广泛活性背后机制的已知情况。