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# Chapter 7: The Complement System The complement system is a complex enzymatic system comprised of approximately 20 proteins, including C1, C2, and C3. These exist in an inactive state in the plasma, and must be cleaved to form active enzymes. ## Synthesis and Activation Synthesis occurs in the...

# Chapter 7: The Complement System The complement system is a complex enzymatic system comprised of approximately 20 proteins, including C1, C2, and C3. These exist in an inactive state in the plasma, and must be cleaved to form active enzymes. ## Synthesis and Activation Synthesis occurs in the liver, intestinal cells, and macrophages. The complement is activated sequentially in a cascading manner. Each protein activates the protein that follows. Complement activation may occur through the classical pathway, the lectin pathway, or the alternative pathway. These 3 pathways lead to production of C3b (the central molecule of the complement cascade). During activation, the complement components are cleaved into fragments. The larger one designated "b" joins the preceding activated components to form a new enzyme. The smaller fragments designated "a" are released in the serum and body fluids helping in certain inflammatory processes. ### Complement Activation Pathways * **Classical Pathway:** is initiated by antigen-antibody complexes, only IgG and IgM activate the complement. The reaction starts by binding of the Fc portion of the antibody molecule attached to its specific cellular antigens. C1 is activated and forms an enzyme that activates C4, followed by C2, then C3. Then C3b binds to C5, C6, C7, C8 and multiple copies of C9 to form the "membrane attack complex" (C5b6789) which causes cell lysis. * **Alternative Pathway:** It is activated in the absence of antibody as a result of complement binding directly on the surface of infectious agents, e.g. bacterial endotoxins and fungal zymosan cell wall. This pathway bypasses C1, C4 and C2, so these antigens directly activate C3 through the properdin system (see chapter 2) which is followed by activation of C5, then formation of "membrane attack complex" (C5b6789). * **Lectin Pathway:** starts with mannan-binding lectin (MBL). A protein that is produced by the liver, can initiate the complement cascade by binding to carbohydrate on pathogen surfaces then activation of C2 & C4 then follow the cascade like the classical one.