Classical complement pathway. The latest step of complement activation is also controlled by the membrane-associated complement regulatory protein CD59 that. Complement Activation Pathways information: The complement system is an enzyme cascade that is a collection of blood and cell surface proteins to help the abilities. It has been known for several decades that the complement system plays a central role in the inflammatory response and tissue/organ injury that follows direct immune recognition by Abs as well as in processes such as organ ischemia/reperfusion (I/R) (reviewed in Ref.1). However, while we know an. IgM or IgG Binds to Antigen 2. C1 binds Antibody 3. C1q is activated (through globular heads) → 4. C1r is activated → 5. C1s is activated 6. C1s cleaves C4 into C4a and C4b 7. ![]() ![]() C4b deposition on surface 8. C1s cleaves C2 into C2a and C2b 9. ![]() ![]() ![]() C2b binds to C4b creating the C3 CONVERTASE OF THE CLASSICAL PATHWAY 10. C3 Convertase cleaves C3 into C3a and C3b 11a. C3b can Opsonize the surface (bind multiple times), marking the antigen for destruction 11b. C3b also binds to the C3 Convertase creating the C5 CONVERTASE OF THE CLASSICAL PATHWAY -Rest of Pathway Covered Later. C3 is hydrolyzed to iC3/C3(H₂O) 2. C3 is bound by Factor B 3. Factor D cleaves Factor B into Ba and Bb 4. Ba goes into solution; Bb remains bound to iC3/C3(H₂O), creating the SOLUBLE C3 CONVERTASE OF THE ALTERNATIVE PATHWAY → Still in Solution 5. Bb cleaves iC3/C3(H₂O) into C3a and C3b 6. C3a goes into solution, C3b binds to the surface of the cell it is near → Does not have to be antigen; unspecific 7. C3b is similar in structure to iC3/C3(H₂O), so Factor B binds 8. Factor D cleaves Factor B into Ba and Bb 9. Bb remains bound to C3b, creating the MEMBRANE-BOUND C3 CONVERTASE OF THE ALTERNATIVE PATHWAY 10. PROPERIDIN binds to the C3 Converstase, stabilizing it so that it may cleave many more C3's 11a. C3b can Opsonize the cell surface 11b. C3b can also bind to the C3 Convertase multiple times, creating the C5 CONVERTASE OF THE ALTERNATIVE PATHWAY. Non-activating capture of complement initiators (e.g. Igs) Inactivation or depletion of complement components by secreted proteases Recruitment of complement regulators to the pathogen surface or secretion of regulator mimics Molecular inhibition of convertase activity Interference with MAC formation Competitive & antagonistic prevention of immune signaling Enter cells by binding cell-bound complement receptors & regulators via pathogen-expressed surface proteins or via C3b fragments deposited on their surface.
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May 2018
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