Complement System

Question 1

What is the complement system

Answer 1

Effector system of the humoral response (both innate and adaptive)

Question 2

What are the 4 roles of complement system proteins

Answer 2

Act as opsonins - opsonisation then phagocytosis via receptor activation

Some recruit phagocytes for inflammation (chemokines)

Some activate B cells to produce antibodies

Some make up MAC for cell lysis

Question 3

What are the 3 pathways

Answer 3

Classical

Alternative

Lectin

Question 4

What initiates classical pathway

Answer 4

Antigen and antibody complex

Question 5

Which complements make up classical pathway

Answer 5

C1 (q,r,s)

C4 , C3 and C2

Question 6

Which complements are in alternative pathway

Answer 6

Factor D,B,P

Question 7

Which complement is in both alternative and classical pathway

Answer 7

C3

Question 8

Which enzyme is produced in all 3 pathways

Answer 8

C3 convertase

Question 9

What are complements cleaved into

Answer 9

a and b fragments

A are always smaller
B are larger

(Apart from in C2 A = large)

Question 10

What do a and b fragments do

Answer 10

Inflammation = a

B = opsonins and surface binding

Question 11

Which opsonin is produced from C3 convertase (why it’s so important)

Answer 11

C3b

Question 12

Why complement binds to the antibody via globular heads

Answer 12

C1q (part of the c1)

Question 13

How does c1 q bind to antibodies

Answer 13

Fc binding globules on antibodies

Question 14

What is the c1 complex made of

Answer 14

2 x s

2 x r

1 x q

Question 15

Which antibody has 5 fc binding globules (meaning only 1 needed to bind c1 q)

Answer 15

Igm

Question 16

Why are 2 igg needed for c1 q to bind

Answer 16

IgG are smaller and 2 globular heads of c1 q need to bind to be activated

Question 17

What is activated (conformation change) via c1 q binding to antibody and what happens

Answer 17

C1 r

This then cleaves c1 s to activate it

Question 18

What is c1 s

Answer 18

A serine protease

Question 19

Explain the events which lead to c4b2a (C3 convertase)

Answer 19

C1s cleaves c4 into c4 a and b

C4a goes to inflammation site

C4 b binds to the pathogen and then c2 is recruited

C2 is also cleaved via c1s protease

C2a (large fragment) then binds to c4b = C3 convertase

Question 20

What does the c4b2a then cleave

Answer 20

C3 into C3a (inflammation) and c3b (opsonin)

Question 21

Which bond on c3b (exposed via c4b2a cleavage) allows into to bind as an opsonin to pathogen

Answer 21

Thioester bond

Question 22

How does c3b also cause phagocytosis

Answer 22

Via c3b receptors

Question 23

What is produced if c3b binds to c4b2a (C3 convertase)

Answer 23

Produces C5 convertase

Question 24

What does c5 convertase (c4b2ac3b) do if c5 binds

Answer 24

Cleaves it to c5a for inflammation

C5b then can bind to pathogen recruiting c6,7,8,9 = MAC

Question 25

What does c 5,6,7,8,,9 form which kills pathogen

Answer 25

A pore by displacing membrane lipids (mac complex)

Question 26

What activates alternative pathway

Answer 26

C3b opsonin binding to pathogen surface

Question 27

What produces the C3 convertase in the alternative pathway

Answer 27

factor B binding to c3b on pathogen surface The factor B is then cleaved by factor D Bb and 3b then bind (c3bBb) to produce C3 convertase

Question 28

Which factor stabilises the c3bBb convertase to surface

Answer 28

Factor P

Question 29

How is c5 convertase produce from c3bBb

Answer 29

Another c3b is added to surface forming c3b2Bb = c5 convertase

Question 30

How is production of c5 convertase c3b2Bb in the alternative pathway allowing recruitment of mac

Answer 30

Cleaves c5 into c5a for inflammation and c5b which binds to 6,7,8,9 = mac

Question 31

What are lectins and where are they made

Answer 31

Carb binding Proteins made in liver

Question 32

What do lectin recognise on pathogens

Answer 32

Mannose Forming mannose binding lectin complex (MBL)

Question 33

What are produced from the MBL complex

Answer 33

Masp 1 and 2 (mannose serine protease)

Question 34

How is C3 convertase c4b2a produced from masp

Answer 34

They cleave c4 and c2 C4b and c2a bind

Question 35

What happens once the C3 convertase c4b2a in lectin pathway is produced

Answer 35

Cleaves C3 into C3 a and c3b C3b can be an opsonin and also bind to c4b2a to form a c5 convertase This c5 convertase can then cleave c5 and c5b recruits 6,7,8,9 = mac

Question 36

Why complement has chemotaxis properties for inflammation eg increase permeability

Answer 36

C1s

Question 37

What would happen if someone had C3 deficiency

Answer 37

Can’t produce c3b to be opsonin which can’t then bind to c4b2a to produce a c5 convertase = no cytolysis for mac

Question 38

What do C1 inhibitors do

Answer 38

Bind to the qrs to stop classical pathway Also remove MBL so that masp can’t be produced

Question 39

Which regulator binds to c4b which displaces c2a and C3b or Bb(in alternative pathway)

Answer 39

Complement receptor 1

Question 40

What does factor 1 regulator cleave

Answer 40

C3b and c4b