the complement system

Question 1

what is the complement system?

Answer 1

a family of plasma and cell associated proteins
consists of a series of inactive precursor proteins
a cascade of proteins

Question 2

what are the 3 proteolytic cascades of the complement system?

Answer 2

classic
alternative
lectin

Question 3

what does complement activation lead to?

Answer 3

proinflammatory mediators
opsonisation
cell lysis by the membrane attack complex

Question 4

what binds to the Fc region of antibodies during the classical pathway?

Answer 4

C1

Question 5

what does C1 consist of? (classical pathway)

Answer 5

C1q
C1r
C1s

Question 6

what does the binding of C1q to the Fc region activate?

Answer 6

proteases C1r and C1s

Question 7

what does C1s cleave C4 into? (classical pathway)

Answer 7

C4a

C4b

Question 8

what happens to C4a and C4b after C4 has been cleaved?

Answer 8

C4b binds to target cell membrane
also binds C2
C4a diffuses away and has inflammatory properties

Question 9

what is C2 cleaved by and what is it cleaved into?

Answer 9

cleaved by C1s

into C2a and C2b

Question 10

what happens to C2a and C2b after cleavage of C2?

Answer 10

C2a remains bound to C4b forming C4b2a

C2b diffuses away

Question 11

what cleaves C3 and what are the products of the cleavage?

Answer 11

C4b2a cleaves it

producing C3a and C3b

Question 12

what happens to C3a and C3b after cleavage of C3?

Answer 12

C3a diffuses away and has inflammatory properties

C3b binds to target cells and acts as an opsonin enhancing phagocytosis by macrophages via complement receptors

Question 13

what is formed when some C3b binds to C4b2a and what does it cleave?

Answer 13

forms C4b2a3b

cleaves C5 into C5a and C5b

Question 14

what happens to the products of C5 cleavage?

Answer 14

C5a diffuses away and has inflammatory properties

C5b binds to target cell

Question 15

what forms the membrane attack complex?

Answer 15

C5b binding C6, C7, C8 and C9

Question 16

what is the membrane attack complex?

Answer 16

a pore that allows water to enter the cell resulting in cell lysis

Question 17

what bind to PAMPs in the lectin pathway?

Answer 17

mannose binding proteins and ficolins

Question 18

what are PAMPs and where are they found?

Answer 18

pathogen associated molecular patterns

found on microorganisms

Question 19

what binds to mannose binding lectin on cell surface in the lectin pathway? what does this complex cleave?

Answer 19

MBL associated serine proteases 1,2 and 3

cleaves C4 into C4a and C4b
and C2 into C2a and C2b

Question 20

what happens after the formation of C4b in the lectin pathway?

Answer 20

allows events to proceed as in the classical pathway

Question 21

what happen to C3 in the alternative pathway?

Answer 21

it is unstable and so undergoes spontaneous hydrolysis to form C3a and C3b

Question 22

what is the fate of C3b in the alternative pathway?

Answer 22

some binds to self cells and is inactivated by regulatory proteins on the cell surface
also able to bind to microbial cells and in turns binds to Factor B
can act as an opsonin or can bind with C3bBb to form C3bBb3b

Question 23

what is Factor B which is bound to C3b cleaved by and what does it form?

Answer 23

cleaved by Factor D

forms Ba and Bb

Question 24

what happens to Ba and Bb in the alternative pathway?

Answer 24

Ba diffuses away

Bb binds C3b forming C3bBb

Question 25

what can C3bBb cleave and what does it form?

Answer 25

can cleave further C3 forming an amplification loop

Question 26

what can C3bBb3b act as?

Answer 26

as a C5 convertase

Question 27

what occurs once C5a and C5b has been formed in the alternative pathway?

Answer 27

classical pathway is followed to form the MAC