Classical Complement Pathway - Immune Response

Classical Complement Pathway: Activated by antigen-antibody (Ag-Ab) complexes aka immunity complex Couples the innate and adaptive immune systems Targets extracellular pathogens important in opsono phagocytosis Adaptive Immune Response Pathway relies on antibodies Steps: Antigen binds to antibody Signals C1q Complement protein C1 binds to immunity complex Must be bound to 2 complexes C1q, bound to immunity complex, activates C1r and C1s C1s cleaves C4 into C4a and C4b C1s cleaves C2 into C2a and C2b C4b and C2a bind to form C3 convertase C3 convertase cleaves C3 into C3a and C3b C3b binds with C3 convertase to form C5 convertase C5 convertase cleaves C5 into C5a and C5b C5b signals molecules for the terminal pathway Collectively known as the membrane attack complex (MAC) Final step of all 3 pathways Terminal Pathway: C5b binds C6, C7, C8, C9 Formation of pore Loss of cell membrane integrity (lysis) Influx of chemical mediators into cell Leads to cell death C3a and C5a - collectively known as anaphylatoxins; induce inflammation and are connected to anaphylactic shock bind to various cell receptors, causing effects to other immune cells **induces inflammation** which causes an **inflammatory response** bringing in many other cells opsonization: makes more susceptible to phagocytosis "make tasty" making more visible to immune system mannose binding lectin complement pathway: (MBL) lectin: protein that binds to sugar mannose: an important component in cell walls of bacteria MBL associates with MBL-associated proteins (MASP) specifically MASP-2 MBL pathway is almost identical to classical pathway EXCEPT MBL/MASP-2 complex cleaves C4 and C2, forming C3 convertase **Innate immune Response:** recognition of bacteria alternative pathway tickover: expressed constantly in small rates BUT can be amplified activated through - tickover **PAMPs** such as LPS damaged tissue primed to respond quickly and vigorously to pathogens or injury (amplification loop) can be activated by the Classical pathway. aids in amplification targets extracellular pathogens of diverse types dysregulation contributes to debilitating and life-threatening disease Full phase 1: C3 contains a strained thiester bond Sometimes the strained thiester bond weakens Shearic strain can put enough pressure on the bond for spontaneous breaking to occur Factor D Tickover: C5 undergoes spontaneous hydrolysis (windsb) to become C3(H2O) may look to bind with -OH or NH pathogens have a lot of OH and NH C3(H2O) binds to factor B becomes C3(H2O)B Properdin factor D cleaves factor B, forming C3 convertase C3 convertase CLEAVES C5 into C3a and C3b Cell C3b BINDS to the microbial surface factor B BINDS to C3b on the microbial surface CL C3b-Factor B is CLEAVED by factor D, forming membrane-bound C3 convertase membrane-bound C3 convertase is stabilized by factor P/Properdin Amplification Step: C3 convertase cleaves multiple C3 into C3a and C3b - goes back into steps 4-9 an additional C3b binds to C3 convertase, forming C5 convertase C5 convertase CLEAVES C5 into C5a and C5b C5b attracts MAC molecules terminal pathway Regulating Proteins: protect our cells from complement decay-accelerating factor (DAF) membrane bound affects classical, lectin, and alternative pathways Accelerates the dissociation of membrane-bound C3 convertase Factor H soluble alternative pathway: blocks the formation of or accelerates the dissociation of C3 convertase all pathways: cofactor for factor I in C3b degradation