4. Complement

Question 1

3 Arms of Complement path

Answer 1

Classical

Lectin

Alternative

Question 2

The first steps of the classical pathway

Answer 2

C1q binds to the Fc portion of immunoglobulins

activation of C1r

C1r activates C1s

cleavage of C4 and C2

forms C4bC2a

Question 3

The first steps of the lectin pathway…

Answer 3

MBL binds to carbohydrate groups on the surface of a bacterial cell

MASP2 activates C4 and C2

forms C4bC2a

Question 4

The first steps of the alternative pathway…

Answer 4

Activated C3b binds factor B

factor B is cleaved into Bb by factor D

forms C3bBb

Question 5

Why are there 3 arms of the complement?

Answer 5

classical arm = recognises bacterial surface antigens

lectin arm = recognises unusual bacterial surface sugars

alternative arm = constant surveillance of bacterial surfaces that lack Complement regulatory proteins

Question 6

C3b forms a C5 convertase

Answer 6

Alternative pathway = C3bBb recruits a further C3b to become a C5 convertase

Classical/lectin pathway =C4bC2a recruits C3b to become a C5 convertase

C5 convertase cleaves C5 into C5a and C5b

Question 7

C5b directs MAC Formation

Answer 7

C6, C7 and C8 are recruited to C5b

C8 directs the recruitment of C9 proteins that insert into the bacterial membrane and form a pore

Question 8

Other functions of Complement

Answer 8

stimulate mast cell degranulation

activate phagocytes

recruit neutrophils by chemotaxis

Question 9

C1 Inhibitor

Answer 9

binds to activated C1r, C1s

removing them from C1q

Question 10

C4BP

Answer 10

Bind C4b

displacing C2a

Question 11

CR1

Answer 11

Binds C4b, displacing C2a

Binds C3b, displacing Bb

Question 12

Factor H

Answer 12

Binds C3b

displacing Bb

Question 13

Factor I

Answer 13

Cleaves C3b and C4b

Question 14

DAF

Answer 14

displaces Bb from C3b

displaces C2a from C4b

Question 15

MCP

Answer 15

inactivates C3b and C4b

Question 16

CD59

Answer 16

prevents formation of membrane-attack complexes

Question 17

Clearance of bacteria via CR1

Answer 17

C5a activates macrophages

phagocytosis occurs via CR1

opsonisation

Question 18

CR1: Clearance of immune complexes

Answer 18

bound C3b binds to the receptor CR1 on erythrocyte surfaces in the spleen and liver

phagocyte cells remove the immune complexes

Question 19

C1q deficiency

Answer 19

systemic lupus erythematosus

C1q Treatment – plasmaphersis

Question 20

C2 deficiency

Answer 20

recurrent pyogenic infections

life-threatening septicaemia

Question 21

Systemic lupus erythematosus

Answer 21

Secondary complement Disorder

Complement is consumed via the classic pathway

Patients have ↓ C3 + C4 levels

Question 22

Hypocomplementemic glomerulonephritis

Answer 22

Secondary complement Disorder

Serum contains NeF

NeF causes activation of the alternative pathway

NeF binds and stabilizes C3bBb

prevents its dissociation by factor H