The complement system

Complement activation represents a well preserved innate immune response, which is able to act fast, within seconds to minutes, as well as sustainable (over days).

During acute inflammation, the complement system can be activated by at least three well known pathways: The classical pathway, the lectin or mannose binding lectin (MBL) pathway and the alternative pathway. The classical pathway is activated e.g. by antigen-antibody complexes that react with activated C1q. The lectin pathway is initiated by either serum MBL or ficolins that recognize certain oligosaccharide moieties on microbial surfaces. The alternative pathway can be activated either by the presence of foreign surfaces such as lipopolysaccharides or through C3b generated by spontaneous hydrolyses, the so-called “tick-over”. All three pathways merge at the level of C3 and activation of either pathway ultimately results in generation of potent pro-inflammatory complement split products such as C3a and C5a as well as the terminal membrane attack complex (MAC).


The three major complement pathways