Classical complement pathway

Classical and alternative pathways shown with their corresponding proteins

The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and IgM.[1][2]

Following activation, a series of proteins are recruited to generate C3 convertase (C4b2b, historically referred C4b2a), which cleaves the C3 protein. The C3b component of the cleaved C3 binds to C3 convertase (C4b2b) to generate C5 convertase (C4b2b3b), which cleaves the C5 protein. The cleaved products attract phagocytes to the site of infection and tags target cells for elimination by phagocytosis. In addition, the C5 convertase initiates the terminal phase of the complement system, leading to the assembly of the membrane attack complex (MAC). The membrane attack complex creates a pore on the target cell's membrane, inducing cell lysis and death.[2][3]

The classical complement pathway can also be activated by apoptotic cells, necrotic cells, and acute phase proteins.[1][3][4]

  1. ^ a b Noris, Marina; Remuzzi, Giuseppe (November 2013). "Overview of Complement Activation and Regulation". Seminars in Nephrology. 33 (6): 479–492. doi:10.1016/j.semnephrol.2013.08.001. PMC 3820029. PMID 24161035.
  2. ^ a b Cite error: The named reference Complement in disease was invoked but never defined (see the help page).
  3. ^ a b Nesargikar, Prabhu; Spiller, B.; Chavez, R. (June 2012). "The complement system: History, pathways, cascade and inhibitors". European Journal of Microbiology & Immunology. 2 (2): 103–111. doi:10.1556/EuJMI.2.2012.2.2. PMC 3956958. PMID 24672678.
  4. ^ Thielens, Nicole M.; Tedesco, Francesco; Bohlson, Suzanne S.; Gaboriaud, Christine; Tenner, Andrea J. (June 2017). "C1q: A fresh look upon an old molecule". Molecular Immunology. 89: 73–83. doi:10.1016/j.molimm.2017.05.025. PMC 5582005. PMID 28601358.