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
what are the 3 main functions of the complement system
- destroy invading pathogens via phagocytosis
- initiate localized inflammatory response
- Membrane Attack Complex
effects of C3a, C4a and C5a
- they bind to receptors on endothelial and mast cells to produce inflammation
- C5a acts on neutrophils to increase adherence
What are the regulatory mechanisms of the complement system
- C1 inhibitor
- Factor I
- Factor H
- DAF, C4BP, CR1
- CD59
how does C1 inhibitor work
dissociates C1r and C1s from the active C1 complex
role of Factor I in regulation of complement
inactivates C3b by cleaving it to iC3b
role of Factor I in regulation of complement
inactivatesC3b by cleaving it to iC3b
role of DAF, C4BP, CR1 in regulation of complement
displace C2a from C4bC2a complex
role of CD59 in regulation of complement
prevents the final assembly of MAC at C8-9 stage
waht is Atypical hemolytic uremic syndrome
mutations of Factor I, Factor H or MCP
* unable to effectively regulate complement
* leads to damage of platelets and RBCs
what is Accelerated macular degeneration
leading cause of blindness in elderly
* base change in factor H genes
* complement is activated on host photoreceptors
