Complement....

Question 1

What are the three effector mechanisms of complement?

Answer 1

• Opsonisation
• Initiates inflammatory response
• Membrane attack complex

Question 2

What is the lytic pathway?

Answer 2

(Bit of a trick question) - it’s the last bit of C’ when C5 is cleaved into C5a and C5b and then accepts C6,7 and 8 for C5b678(9)n to form

Question 3

How does the MAC actually form?

Answer 3

C5b678 lodges itself into the membrane of the foreign/infected cell and then C9 forms this ring-like structure which, when attached to C5b678, punches holes into the membrane which causes the cell to lyse due to osmotic shock (it explodes)

Question 4

Why doesn’t Mannose Binding Lectin bind to self cells?

Answer 4

It uses patterns of spacing between adjacent mannose sugar residues to differentiate self from non-self. Pathogen mannose sugar residues are much closer together than ours!

Question 5

What happens in the classical pathway?

Answer 5

1. C1 cleaves C2 and C4 into a and b subunits
2. C4b binds to bacterial surface and C2a kisses C4b to make C4b2a aka C3 convertase (enzyme)
3. C3 convertase cleave C3 into C3a and C3b
   Note: C3b is an opsonin (Y) but it also binds stuff too
4. Make C4b2a3b = C5 convertase
5. C5 convertase cleaves C5 into C5a and C5b
6. Follow lytic pathway to MAC

Question 6

What happens in Lectin pathway?

Answer 6

1. MBL cleaves C4 into C4a and b
2. C4b binds C2a (don’t ask me how, it just does)
3. Follow classical pathway (pasted below):
4. C3 convertase cleave C3 into C3a and C3b
   Note: C3b is an opsonin (Y) but it also binds stuff too
5. Make C4b2a3b = C5 convertase
6. C5 convertase cleaves C5 into C5a and C5b
7. Follow lytic pathway to MAC

Question 7

What happens in the alternative pathway?

Answer 7

1. C3 gives up and spontaneously splits into C3a and C3b (v. slow process)
2. Factor B binds C3b = C3bFB
3. Factor D cleaves Factor B into Ba and Bb = C3bBb = C3 convertase (not the same as the other one but called the same thing because of its function)
   * *Must be stabilised by properdin (good luck remembering that)
4. C3 convertase –> C3a and C3b, C3b adds on so it becomes C3bBb3b = C5 convertase
5. C5 convertase is the only normal thing is this pathway so its all the same from here on (lytic pathway)

Question 8

What are the anaphylatoxins?

Answer 8

• C3a, C5a, C4a

- I’m not entirely sure what they do.. maybe get the neutrophils around them? do a dance? who knows..

Question 9

How is the classical/lectin pathway regulated?

Answer 9

• C4bBP blocks C2a binding (BP = blocking protein)

- Factor I then cleaves C4b into C4c and C4d

Question 10

How is the alternative pathway regulated?

Answer 10

• Factor H blocks Factor B binding

- Factor I cleaves C3b into C3c and C3d

Question 11

How is the lytic pathway regulated?

Answer 11

• S protein blocks C8 binding to C567

- HRF (homologous restriction factor) blocks C9 polymer binding to C5b678

Question 12

How can pathogens evade complement?

Answer 12

- Long O-polysaccharide chains:
Deposit C3b at sites distant from bacterial surface
Inability of MAC to penetrate membrane
- Protein A:
Binds to Fc portion of IgGs
S. aureus is v good at it