Complement System Flashcards
3 outcomes of complement activation
Opsonization of bacteria
Lysing of bacteria through membrane attack complex
Inflammation and phagocyte recruitment
3 activation pathways
Classical
Lectin
Alternative
What all 3 pathways generate
Enzyme C3 convertase
How classical pathway is initiated
Antibody (IgM or IgG) binds to multivalent antigen
C1 complex binds Fc of antibody
Steps of classical pathway
C1 complex (C1qr2s2) binds antibody
C1s cleaves C4 and C2, making C4b2a (C3 convertase)
C3 convertase cleaves C3 molecules, making C4b2a3b (C5 convertase)
C5 convertase cleaves C5
C5b goes on to form membrane attack complex
Initiation of lectin pathway
Mannose binding lectin binds to mannose residues on bacteria OR ficolins binds to carbohydrate structures on bacteria or fungi
Steps of lectin pathway
MASPs (mannose binding lectin or ficolin) bind to carbohydrates
MASP cleaves C2 and C4, forming C4b2a (C3 convertase)
Rest goes like classical pathway
Initiation of alternative pathway
C3 undergoes autohydrolysis
Steps of alternative pathway
C3 undergoes autohydrolysis
Factor B binds to C3
Factor D cleaves factor B, making C3bBb (C3 convertase)
Properdin binds C3 convertase, stabilizing it
C3 convertase cleaves C3, making C3bBbC3b (C5 convertase)
Formation of membrane attack complex
C6 binds to C5b
C7 binds to C6
C8 binds to C7
Many C9s bind to C8, forming pore that causes lysis of bacterial cell
Opsonization by complement
C3b binds to bacteria, enhancing uptake by phagocytes
Receptors such as C3R on macrophages and neutrophils recognize complement
CD21 on B cells helps bind to complement-coated antigens
Phagocyte recruitment and inflammation
C5a and C3a serve as anaphylatoxins, which promote inflammation
Granulocytes have C3aR and C5aR- binding to these stimulates release of proinflammatory cytokines
Triggers migration of phagocytes to sites of inflammation
