<Li> Inflammation--by attracting macrophages and neutrophils </Li> <Li> Membrane attack--by rupturing cell wall of bacteria </Li> <P> Most of the proteins and glycoproteins that constitute the complement system are synthesized by hepatocytes . But significant amounts are also produced by tissue macrophages, blood monocytes, and epithelial cells of the genitourinary system and gastrointestinal tract . The three pathways of activation all generate homologous variants of the protease C3 - convertase . The classical complement pathway typically requires antigen - antibody complexes for activation (specific immune response), whereas the alternative pathway can be activated by spontaneous C3 hydrolysis, foreign material, pathogens, or damaged cells . The mannose - binding lectin pathway can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response). In all three pathways, C3 - convertase cleaves and activates component C3, creating C3a and C3b, and causes a cascade of further cleavage and activation events . C3b binds to the surface of pathogens, leading to greater internalization by phagocytic cells by opsonization . </P> <P> In the alternative pathway, C3b binds to Factor B. Factor D releases Factor Ba from Factor B bound to C3b . The complex of C3b (2) Bb is a protease which cleaves C5 into C5b and C5a . C5 convertase is also formed by the Classical Pathway when C3b binds C4b and C2b . C5a is an important chemotactic protein, helping recruit inflammatory cells . C3a is the precursor of an important cytokine (adipokine) named ASP (although this is not universally accepted) and is usually rapidly cleaved by carboxypeptidase B. Both C3a and C5a have anaphylatoxin activity, directly triggering degranulation of mast cells as well as increasing vascular permeability and smooth muscle contraction . C5b initiates the membrane attack pathway, which results in the membrane attack complex (MAC), consisting of C5b, C6, C7, C8, and polymeric C9 . MAC is the cytolytic endproduct of the complement cascade; it forms a transmembrane channel, which causes osmotic lysis of the target cell . Kupffer cells and other macrophage cell types help clear complement - coated pathogens . As part of the innate immune system, elements of the complement cascade can be found in species earlier than vertebrates; most recently in the protostome horseshoe crab species, putting the origins of the system back further than was previously thought . </P>

Where does the activation of complement system take place
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