Complement

Question 1

In the 1890’s what did Border demonstrate using serum from an animal?

Answer 1

He demonstrated that serum from an animal that was immunized to cholera was able to lyse bacteria

Question 2

What was complement originally identified as?

Answer 2

The heat liable component

Question 3

What two components did Jules Bordet find?

Answer 3

Component 1 - Ab

• Heat stable
• Specified “remembered”

Component 2 - Complement

• Heat liable :(
• Kills pathogen

Question 4

What enhances target lysis?

Answer 4

Adding component 2 to component 1

“complemented Ab”

Question 5

What did Bordet call component 2?

Answer 5

Alexin

Question 6

What does the complement system consist of?

Answer 6

> 30 soluble plasma proteins and membrane-bound components

Question 7

What is required for the activation of complement?

Answer 7

A cascade of proteolytic events performed by serine protease domains

Question 8

What type of process is complement?

Answer 8

Tightly regulated because it is powerful

More than half of the 30+ components are negative regulators of activation

Question 9

Complement facilitates what two things?

Answer 9

1. Lysis of target

2. Opsonin - labels target so it can be phagocytosed

Question 10

What are the three pathways that complementation can occur through?

Answer 10

1. Classical (Ab activated)
2. Alternative (spontaneous)
3. Lectin (doesn’t use Ab)

Question 11

What is the goal of all thre pathways?

Answer 11

C3 and then C5

Question 12

What does the cleavage of complement proteins yield?

Answer 12

2 fragments

Question 13

What is the a and b fragment?

Answer 13

Large is b

Small is a

Question 14

Give an example of C3 fragments

Answer 14

C3 -> C3a (small) and C3b (large)

Question 15

What is the excpetion to large/small fragments?

Answer 15

C2
C2a is large
C2b is small

Question 16

What do the larger fragments do?

Answer 16

Large fragments bind to nearby targets and is proteolytically active

Question 17

What do the small fragments do?

Answer 17

Diffuse away and act as proinflammatory mediators

Question 18

How is the classical pathway initiated?

Answer 18

The complement protein CI binds to two Fc regions of Ab

2 IgG or 1 pentameric IgM

Question 19

What 3 things is C1 comprised of?

Answer 19

C1q (binds Ab)
C1r (regulatory)
C1s (serine protease - cuts)

Question 20

What does binding to Ab induce?

Answer 20

A conformational change in C1, exposing an active enzymatic site that is able to cleave and activate C4 and C2

Question 21

What does C1 cut?

Answer 21

C4 and C2

Question 22

What do C4 and C2 do?

Answer 22

They associate to form the C3 Convertase

Question 23

Is C1 cleavage of C4 efficient?

Answer 23

Yes, bc there are high levels of C4

Question 24

What happens to C4 once it is cleaved?

Answer 24

C4b is quickly inactivated by iC4b

Some C4b lands on a nearby surface and remains proteolytically active

Question 25

Is the cleavage of C2 efficient?

Answer 25

Not really, bc there are lower conc.

Question 26

How does C2 compensate for its low serum conc.

Answer 26

C2 binds to C4b on the target surface

Question 27

What facilitates the cleavage of C2?

Answer 27

C2 binding to C4b bc it brings it in close proximity to the active C1

Question 28

What part of C2 is active?

Answer 28

C2a stays with C4b

Question 29

What is C4b2a called/

Answer 29

C3 convertase

Question 30

What does the C3 convertase do?

Answer 30

Cleaves C3, releasing C3a and C3b stays associated w/ target surface

Question 31

Describe C3a

Answer 31

Inflammation

Long-lasting anaphylatoxin which is capable of acting on targets distant to its site of generation

Question 32

Describe C3b

Answer 32

Keystone molecule

• Short lived (60ns)
• Dangerous, so shut down quick
• Some remains associated w/ C4bC2a producing the C5 convertase (C4bC2aC3b)

Question 33

What happens to C3b that is not covalently bound to a target surface?

Answer 33

It is inactivated through hydrolysis (iC3b)

Question 34

What is C4bC2aC3b?

Answer 34

C5 convertase