Complement proteins

Question 1

3 complement pathways

Answer 1

Classical, Lectin, Alternative

Question 2

Which pathway involves antibodies

Answer 2

Classical:

C1q binds to pathogen Or Ag:Ab complex

Question 3

What induces lectin pathway

Answer 3

MBL or ficolin binding to carbohydrates on pathogen surface

Question 4

What induces alternative pathway

Answer 4

Soluble C3 undergoes spontaneous hydrolysis

Question 5

Function of complement

Answer 5

• Bacterial cell wall lysis (MAC)
• Opsonisation
• Recruitment of neutrophils (chemotaxis)
• Activation of mast cells + basophils
• Removal of immune complexes

Question 6

Function of C3b

Answer 6

• bind to C3 convertases to form C5 convertases
• opsonin
• binds to Factor B, which is cleaved to Bb (by factor D). Properdin stabilises C3b-Bb complex: inflammation, phagocytosis, neutralisation of viruses

Question 7

Function of C5, 6, 7, 8, 9

Answer 7

Formation of MAC (membrane attack complex)

C5b + 6 + 7: bind to membrane via C7

C5b + 6 + 7 + 8: insert into cell membrane

C5b + 6 + 7 + 8 + 9: polymerises, forms pore in in membrane (with multiple C9 molecules).

Leads to cell lysis due to entry of water and Na+

Question 8

Role of anaphylotoxins (C3a, C4a, C5a)

Answer 8

• local inflammatory response
• increase vascular permeability
• smooth muscle contraction
• induction of adhesion molcules
• recruitment of phagocytes to inflammation site

Question 9

Describe complement mediated phagocytosis

Answer 9

1. Cr1 on macrophage binds C3b on bacterium
2. Endocytosis of bacterium by macrophage
3. When antibody binds to Fc receptor, bacteria are phagocytosed
4. Lysosomes fuse with these vesicles, delivering enzymes that degrade the bacteria

Question 10

What happens to Ag:Ab complexes formed in circulation

Answer 10

CR1 on erythrocytes bind Ab:Ag complexes via bound C3b

Ag:Ab complexes removed to spleen and liver where cells remove the immune complexes from the erythrocyte surface

Question 11

Complement proteins + protease involved in classical pathway

Answer 11

C1q, C4, C2

Protease: C1s

Question 12

Complement proteins + protease involved in lectin pathway

Answer 12

C2, C4

Protease: MASP2

Question 13

Complement proteins + protease involved in alternative pathway

Answer 13

C3

Protease: Factor D

Question 14

Effect of CD59 on MAC formation

Answer 14

Prevents final assembly of MAC at the C8 to C9 stage

Question 15

Where are most complements made

Answer 15

Liver (not stem cell).

Thus BM transplant would not be effective for complement deficiency patients.

(BM transplant would work for CGD where phagocytes do not have working NADPH oxidase)