Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complement
- 作者：Pangburn ; Michael K.
- 关键词：Factor H ; Alternative complement pathway ; Innate immunity ; SCR domains ; Complement regulatory proteins ; AP ; the alternative pathway of complement activation ; SCR ; short consensus repeats which are domains approx. 60 amino acids in length found in many com
- 刊名：Immunopharmacology
- 出版年：2000
- 期刊代码：43_01623109
- 类别：imm
- 出版时间：August, 2000
- 卷：49
- 期：1-2
- 页码：149-157
- 文件大小：969 K
摘要
Factor H is responsible for recognition of host cells and tissues and mediates discrimination among microbial pathogens during activation of the alternative pathway of complement (AP). Its unique structure of 20 SCR domains arranged in a flexible chain permits a variety of functional sites to interact with complement proteins and surface markers in a biological example of single-molecule combinatorial chemistry. In addition to the complement regulatory site located in the N-terminal four SCR domains, two other sites bind complement protein C3b and three sites appear to recognize a variety of polyanions that serve as host markers. Recent studies indicate that cooperativity among several C3b- and polyanion-binding sites influences the biological functions of factor H and that the degree of influence of each site varies on different cells. The engagement of one or more of the host marker recognition sites enables factor H to control activation of the AP. The absence of host-like markers allows AP activation, but many common pathogens have developed receptors for factor H or mimics of host markers of varying degrees of authenticity allowing them to escape detection by this innate defense system. Organisms using one or more of these evasive techniques include Neisseria gonorrhoeae, Streptococcus pyogenes, Yersinia enterocolitica, Trypanosoma cruzi, and the HIV virus.