title: Self-nonself discrimination by the complement system.
abstract: The alternative pathway (AP) of complement can recognize nonself structures by only two molecules, C3b and factor H. The AP deposits C3b covalently on nonself structures via an amplification system. The actual discrimination is performed by factor H, which has binding sites for polyanions (sialic acids, glycosaminoglycans, phospholipids). This robust recognition of 'self' protects our own intact viable cells and tissues, while activating structures are recognized by default. Foreign targets are opsonized for phagocytosis or killed. Mutations in factor H predispose to severe diseases. In hemolytic uremic syndrome, they promote complement attack against blood cells and vascular endothelial cells and lead, for example, to kidney and brain damage. Even pathogens can exploit factor H. In fact, the ability to bind factor H discriminates most pathogenic microbes from nonpathogenic ones.
authors.affiliation: Immunobiology, Research Programs Unit, Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Finland.|HUSLAB, Helsinki University Hospital, Finland.|Humanitas University, Milan, Italy.
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000472:pathogenicity; D001665:Binding Sites; D001930:Brain Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003179:Complement C3b / Q000235:genetics / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D003170:Complement Pathway, Alternative / Q000235:genetics*; D006025:Glycosaminoglycans / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D006801:Humans; D009154:Mutation; D010587:Phagocytosis / Q000235:genetics*; D010743:Phospholipids / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism
chemical_list: C493495:CFH protein, human; D006025:Glycosaminoglycans; D010743:Phospholipids; D012794:Sialic Acids; D003179:Complement C3b; D017242:Complement Factor H
keywords: escape; hemolytic uremic syndrome; sialic acid