Complement Mediated Cell Lysis

Complement Mediated Cell Lysis Background

Complement system is a highly regulated and multifunctional system that is the major extracellular arm of innate immunity. Its activation results in three major potential outcomes for microbes: lysis upon assembly and insertion of the terminal membrane attack complex (MAC), complement mediated opsonization, and the release of anaphylatoxins that enhance local inflammation. Three potential complement activation pathways exist. Surface antigen recognition by IgM or IgG initiates the classical pathway. Surface carbohydrate recognition by soluble lectins initiates the lectin-mediated pathway. Random H2O-catalyzed "tick-over" of C3 initiates the alternative pathway. Each pathway leads to assembly of C3 convertase, an enzymatically active complex formed by the cleavage fragments of upstream components. Both C4b2a (classical and lectin pathways C3 convertase) and C3bBb (alternative pathway C3 convertase) cleave C3a from native C3 to form C3b. A cryptic reactive thioester group within native C3 becomes available on C3b to form covalent linkages with either hydroxyl or amine moieties on microbial acceptor molecules. Bound C3b interacts with parent C3 convertases to form C5 convertases to initiate the terminal lytic pathway leading to insertion of the membrane attack complex (MAC). However, negative regulation of complement activity can result in further cleavage of C3b to smaller, inactive fragments (C3bi, C3dg, or C3d) that do not initiate the terminal lytic pathway. The C3b and C3bi fragments mediate opsonophagocytosis of bound organisms via their recognition by complement receptors (CR) on professional phagocytes. Macrophage CR-mediated entry for intracellular pathogens has long been regarded as a particularly important pathway to enhance survival following phagocytosis.

In some cases, this causes more harm than good; complement-mediated lysis can cause such serious disorders as Rh disease, immune hemolytic anemia and immune thrombocytopenic purpura.

Total Complement Activity / CH50 / CH100 (Proteins | Antibodies | Genes | ELISA Kits)

Other Complement Mediated Cell Lysis Related Products

Complement Mediated Cell Lysis References

1. Clay C D, et al. (2008). Evasion of complement-mediated lysis and complement C3 deposition are regulated by Francisella tularensis lipopolysaccharide O antigen. The Journal of Immunology, 181(8), 5568-5578.
2. Cragg M S, et al. Glennie, M. J. (2003). Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts. Blood, 101(3), 1045-1052.
3. Golay J, et al. (2000). Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro: CD55 and CD59 regulate complement-mediated cell lysis. Blood, 95(12), 3900-3908.
4. Harris S L, et al. (1990). Glycoprotein C of herpes simplex virus type 1 prevents complement-mediated cell lysis and virus neutralization. Journal of Infectious Diseases, 162(2), 331-337.
5. Bindon C I, et al. (1988). Importance of antigen specificity for complement‐mediated lysis by monoclonal antibodies. European journal of immunology, 18(10), 1507-1514.
6. Gordon J, et al. (1981). Antigenic modulation of lymphocytic surface immunoglobulin yielding resistance to complement-mediated lysis. II. Relationship to redistribution of the antigen. Immunology, 42(1), 13.