Lecture 7: Complement Flashcards
what is complement
a collection of soluble proteins present in blood and other body fluids that serves to ‘complement’ antibody activities
*many complement proteins are proteases
when is complement activated
in response to pathogens or antibodies bound to pathogens
what is required in order for complement proteins to become active
proteolytic cleavage of C3—> C3a and C3b
what results in the rapid inactivation of C3b ?
if it becomes unbound to pathogen
what triggers the activation of the Lectin Pathway?
- by pattern recognition receptors MBL (Mannose Binding Lectin) and ficolins
what are the key molecules in the LECTIN pathway
- MBL/Ficolin
- MASP2
- C4
- C2
what are the key molecules in the CLASSICAL pathway
- C1q
- C1r
- C1s
- C4
- C2
what are the key molecules in the ALTERNATIVE pathway
- Factor D
- Factor B
- properdin
- C3
explain the steps in the lectin pathway
- activated MASP2 associated w/ MBL or Ficolin cleaves C4 into C4a + C4b
- C4b binds to microbial surface
- C4b binds to C2
- C2 cleaved by MASP2 —> C2b and C2a
- C4bC2a complex forms
- C4bC2a = C3 convertase
what initiates the classical pathway
IgG binding to an antigen on pathogen surface
what are the 2 ways in which the alternative pathway can be activated
- C3b deposited by classical or lectin pathway C3 convertase
- spontaneous hydrolysis of C3
What is different about the alternative pathway’s C3 convertase
it is C3b bound to Bb
what are the C3 convertases from the classical, lectin and alternative pathways
classical & lectin: C4bC2a
alternative: C3bBb
role of C3b
binds to pathogen, opsonizes it, signals for its destruction
how is C5 convertase formed in each pathway
Classical and lectin: C3b binds C4bC2a –> C4bC2aC3b
alternative pathway: C3b binds C3Bb –> C3bC3bBb
