Complement Flashcards
What two components in blood serum are needed to right pathogens?
Heat-labile = complement
Heat-stable = antibodies
Are antibodies present in all serums?
No, only present in the vaccinated
Is complement present in all serums?
Yes
Where are complement molecules mainly produced?
Liver
What are zymogens?
Proteases secreted as inactive pro-enzymes
How are zymogens activated?
Via proteolytic cleavage by other enzymes
How is the Classical Pathway activated?
Antigen-antibody complex = recognized by C1q
What is the structure of C1q?
Hexamer with collagen-like tail and 6 globular heads
What activates C1r and what does this allow it to do?
Conformational change activates C1r = serine protease
Allowing it to cleave and activate C1s
What cleaves C4 in the Classical Pathway?
C1s cleaves C4 into C4a and C4b
What cleaves C2?
C2 is recognised by C1s and cleaved into C2a and C2b
What makes up C3 convertase?
C4b2a
How are C4b and C2a joined?
Chemically linked
What activates the Alternative Pathway?
Spontaneous hydrolysis of C3
What bond is hydrolysed in C3?
Thioester bond because of its inherent lability
What C3 convertase is formed from Alternative Pathway?
Active initial fluid phase C3 convertase
What does conformational change cause in the Alternative Pathway?
C3(H2O) to bind Factor B
What activates Factor B?
Factor D cleaves Factor B
What is produced from cleavage of Factor B?
Ba and Bb
What makes the fluid-phase C3 convertase?
C3(H2O)Bb
When is Factor B able to be cleaved?
Only when it is bound to C3(H2O)
Where is mannose-binding lectin produced?
Liver
At what concentrations is MBL present in plasma?
Low concentrations in plasma
When does MLBs concentration increase?
During acute-phase reaction
What is the structure of MBL?
Carbohydrate-recognition domain
alpha-helical coiled coil
Collagen helices
What proteins does MBL form a compelx with?
MASP1/2 = MBL-Associated Serine Protease1
What are MASP1/2?
Protease zymogens
What do ficolins bind and with what domain?
N-acetylglucosamine
Fibronectin domain
How does the Lectin Pathway generate C3 convertase?
Mannose residue on pathogen surface = recognized by MBL-MASP1/2 complex
Activates MASP2
MASP2 cleaves C4 and C2
What makes the C5 convertase?
C3 convertase cleaves C3 -> C3a and C3b
C5 convertase = C4b2a3b
How is MAC formed?
C5 convertase cleaves C5
C5b binds C6&7
C7 allows C5b67 to bind to membrane
C8 bind complex and inserts into cell membrane
C9 binds complex and polymerizes
What does C1 inhibitor regulate?
Initiation
Binds active C1r-C1s = causing it to dissociate from C1q
What does DAF regualte?
C3 convertase
Competes with Factor B for C3b = displaces Bb from convertase
What does CR1 regulate?
C3 convertase
Similar to DAF
What does Factor I regulate?
C3 convertase
Cleaves C3b to produce iC3b = inactive
What cofactors work with Factor I?
Membrane Cofactor of Proteolysis (MCP)
Factor H
What does Factor H regulate?
Competes with Factor B to displace Bb
What regualtes C5 convertase?
Protectin = inhibits binding of C9 to C5b678
What does Factor P do?
Properdin binds C3bBb
Enhances its stability
