The Complement system

Question 1

7 Important points about the Complement System

Answer 1

> 40 proteins 
Cascade
Soluble and membrane bound proteins 
Mainly produced in the liver 
Are proenzymes and when activated become a and b parts 
3 pathways
Central molecule is C3

Question 2

Classical pathway: structure

Answer 2

Atg and Ab complex formation
involves C1, C2 and C4

2 C1r and 2 C1s stabilized by Calcium ions
C1q polypeptide chains, have a collagen “stem” and globular “head”

Question 3

Classical pathway: mechanism of action- cluster formation

Answer 3

Cluster formation!

Fc regions of the Igs bound to the Atg are getting closer to each other

Question 4

Classical pathway: mechanism of action- the ab atg complex

Answer 4

The complex forms btw IgM/IgG and the Atg

1. C1q binds to the complex- structural changes
2. C1r undergoes a structural change which causes its activation
3. C1r activates C1s by cleaving it
4. C1s cleaves C4 and C2

Question 5

Lectin activated pathway: structural components

Answer 5

Ficolin
MBL: Mannose Binding Lectin
MASP: MBL Associated Serin Protease

Question 6

What can Ficolin bind

Answer 6

N-acetyl glucosamine on bacterial cell wall

Question 7

What can MBL bind?

Answer 7

Mannose on the microbe surface

Question 8

Mechanism of action of the Lectin activated pathway

Answer 8

1. MBL is bound to the carbohydrates on the surface of the Atg
2. Structural changes activate MASP-1
3. MASP-1 cleaves MASP-2
4. MASP-2 cleaves C4 and C2

Question 9

Structure of MBL and Ficolin

Answer 9

Ficolin has a fibrinogen like domain
MBL has a CRD domain
Both: neck region, collagen-like domain, cysteine rich region

Question 10

Alternative pathway

Answer 10

C3 spontaneous degradation to C3a and C3b

Question 11

Alternative pathway: surfaces

Answer 11

Absence of sialic acid!!
Bacteria
Viruses 
Fungi
Tumour  
Parasites 
Atg-Ea complex (any isotypes)

Question 12

Functions of Properdin

Answer 12

Stabilization of C3 convertase

Amplification of C3b

Question 13

Functions of factor H

Answer 13

Decay of C3bBb

Cofactor for factor I

Question 14

Terminal pathway

Answer 14

1. C5b binds C6 and C7
2. C5b67 bind to membrane via C7
3. C8 binds to this complex and inserts into the cell membrane
4. C9 molecules bind to the complex and polymerize
5. 1-16 molecules of C9 bind to form a pore in the membrane

Question 15

Consequences of Complement Activation

Answer 15

Cell lysis
Inflamm
Opsonization

Question 16

Consequences of Complement Activation: Cell lysis

Answer 16

Carried out by MAC

Question 17

Consequences of Complement Activation: Inflammation (6)

Answer 17

Degranulation of mast cells and eosinophils 
Chemotaxis 
Platelet aggregation
Ne release from BM
Migration inhibition
Increase complement receptor synthesis

Question 18

Consequences of Complement Activation: Opsonization

Answer 18

C3b
C4b
iC3b

Cell activation:

• granulocytes
• B and T-Cells

Question 19

Regulation of the Complement system (6)

Answer 19

C1 inhibitor 
Factor H
Factor I
S protein
DAF
C4b binding protein

Are all soluble except DAF which is membrane bound

Question 20

Regulation of the Complement system: C1 inhibitor

Answer 20

Classical pathway

Protease inhibitor

Question 21

Regulation of the Complement system: Factor H

Answer 21

Alternative pathway
Binds C3b (properdine)

Question 22

Regulation of the Complement system: Factor I

Answer 22

All pathways
Cleaves C3b and C4b
(with cofactors)

Question 23

Regulation of the Complement system: S protein

Answer 23

All pathways

Prevents insertion of C5b67

Question 24

Regulation of the Complement system: DAF

Answer 24

Is the only one that is membrane bound
Acts in all pathways
C4b2b, C3bBb dissociation

Question 25

Regulation of the Complement system: C4b binding protein

Answer 25

Classical and lectin pathways
Blocks C3 convertase formation

*no C3 convertase in the alternative pathway