Complement system Flashcards
What is the complement system?
pathway which acts to protect against infection and inflammation (e.g. processes - stimulate the activity of WBC to defend against pathogens)
What do complement components do? Where are complement components synthesised?
a) they interact w/ each other in a enzyme-triggered cascade ie. most will be a zymogen until they are cleaved => activated to cleave other zymogens
b) liver and inflammatory cells
What are the functions of the complement system? > function of each*
- Production of opsinins > coat bacteria via receptors => stimulate phagocytosis
- Production of anaphylatoxins > stimulate cells where site of inflammation is
- Direct killing of pathogens: by making pores in membrane
* 4. Other functions > remove dead & dying cells; repair
What are the 3 distinct pathways of active complement? & the common result these pathways share
- Classical pathway
- Mannose-binding lectin (MB-lectin) path.
- Alternative path.
=> C3 convertase
What are the 5 nomenclature of the complement system?
- Components of classical path: C1, C4, C2, C3, C5, C6, C7, C8
- Products of cleavage rxns: b for big except C2; a for small except for C2
- Components of alternative pathways: different letters
- MB-lectin: 1st enzymes activated = MASP-1 & -2 (MB-L Associated Serine Proteases
- Convertase: converts inactive zymogen to active
Describe how C3 convertase is formed from the classical pathway?
- C1q bind to Ag-Ab complex* => C1s esterase (can also bind directly on pathogen too - innate)
- C1s esterase cleaves C4 => C4a & C4b (attach on surface of pathogen)
- C4b binds to C2
- C2 cleaved by C1s esterase => C2b (sml) & C2a (attach on surface of pathogen)*
- C2a bind w/ C4b (already on the surface of the bacteria) => C4b2a = C3 convertase
Describe how C3 convertase is formed from the MB-lectin pathway?
- MBL binds to mannose on surface of bacteria
- activates MASP-2
- MASP-2 => cleaves C4 & C2 => C4b2a = C3 convertase
Describe how C3 convertase is formed from the alternative pathway?
- hydrolysis of C3 => C3b in circulation
- C3b binds to -OH groups on proteins & carbohydrates of bact. surface
- Serum factor B binds w/ C3b => C3bB
- Factor D cleaves the B in C3bB => Ba + Bb (attached to C3b = C3bBb = C3 convertase)
- C3bBb rapidly dissociates unless stabilised by properdin => rapidly cleave C3 = lots of C3b
The difference between how the 3 complement systems are stimulated
- Complement pathway: Ag-Ab complex on bact. surface
- MB-lectin pathway: Mannose on bact. surface
- Alternative pathway: pathogen surface
From C3 convertase how is C5 convertase formed? (*Note: same for 3 pathways but C5 convertase is diff. in each)
- C3 convertase cleaves C3 => C3a + C3b
- *C3b binds to C3 convertase => C5 convertase
* classical pathway: C3b + C4b2a => C4b2a3b
* alternative path: C3b + C3bBb => C3bBb3b
How is the membrane attack complex (MAC) formed? (start at C5 convertase)
- C5 convertase cleaves C5 => C5a + C5b (binds to surface of pathogen)
- C5b binds C6 = C5b6 complex
- C5b6 binds to C7 = C5b67 complex]
- complex inserts through lipid by-layer
- C8 binds => penetrate deeper in cell membrane
- C9 molecules interact w/ C5b-8 complex => polymerisation of (10-16) C9 molecules => pore
How can MAC be confined/restricted to surface of pathogens?
- C5b67 complex inserted through lipid by-layer
- when C8 binds to complex, it penetrates deeper in cell membrane
What are the problems asociated w/ a deficiency of C1, C4, C2?
- *C1, C4, C2 from complement pathway
=> auto-immune disease
=> increased infections bc those are important for opsinisation
What are the problems asociated w/ a deficiency in components from alternative pathway?
=> recurrent bact. infections bc those required for opsinisation
What are the problems asociated w/ a deficiency of Factor D & properdin?
=> Neisseria (bact.) infections
