3a. Complement System

Question 1

Complement activation causes what main effects?

Answer 1

Induction of inflammation, opsonization of pathogen and killing of pathogen

Question 2

Characteristics of the complement system

Answer 2

• Ancient
• Humoral (immediate)
• No antigen specificity (innate)

Question 3

How is C3 activated?

Answer 3

Cleaved by a C3 convertase into one small (C3a) and one large (C3b) component

Question 4

How is the classical pathway initiated?

Answer 4

Induced by the presence of antibodies which are docked on the surface of the antigens

Question 5

Initiation of alternative pathway

Answer 5

Doesn’t need any additional molecules. Pathogen surface is free -> alternative pathway starts spontaneously

Question 6

How is the Lectin pathway initiated?

Answer 6

Doesn’t need any additional antibody but needs certain carb chains to be present on the pathogen surface (Lectin molecules)

Question 7

What antibody is the most effective inducer of the classical pathway?

Answer 7

IgM (pentamers)

Question 8

How will the IgM pentamer be activated?

Answer 8

Circulating like a snowflake in inactive forms, transforms to a planar form when connected to a surface -> five Fc regions can bind pathogen

Question 9

Early steps of classical pathway

Answer 9

• C1 complex (consists of C1q, C1s and C1r) connects to Fc region of antibody (IgM)
• C1s activates either C2 or C4 -> C2/4a + C2/4b
• C4b2a = C3 convertase

Question 10

C1 complex

Answer 10

C1q: Binds antibody
C1r: Binds IgM (?)
C1s: and r are proteolytic

Question 11

Early steps of alternative pathway

Answer 11

• C3 is spontaneously cleaved in plasma
• C3b is frequently inactivated by hydrolysis to keep conc. at a normal level
• C3b can bind to microbial surface for activation
• Binds factor B
• factor D cleaves factor B into: Bb and Ba
• C3bBb complex forms C3 convertase
• Amplification by C3 convertase -> C3b binds covalently to cell surface

Question 12

Early steps of Lectin pathway

Answer 12

• Mannose binding Lectin (MBL) binds to mannose containing proteins on pathogens
• MBL + MASP (MBL-associated-serine-protease) cleaves C2 and C4 -> C2bC4b
• cleaves C3 for C3b

Question 13

First steps of late events in the compliment system

Answer 13

Production of C5 convertase (either C4b2a3b or C3bBb3b) –> activation of C5 -> C5b

Question 14

What is the role of C5b?

Answer 14

C5b can dig into the membrane of the pathogen and recruit other complement proteins: C6 and C7 -> Further C8 and C9 is also recruited

Question 15

What does the MAC consist of?

Answer 15

The membrane attack complex consist of C5b, C6-C9

Question 16

What will happen when the MAC is activated?

Answer 16

Lysis of the cell (ions and water can enter the cell through the pore made by the MAC)

Question 17

Effects of C3a, C4a and C5a?

Answer 17

Local inflammatory mediators: anaphylatoxins

- recruitment of inflammatory cells, degranulation of mast cells, activation of granulocytes

Question 18

Why C3 is the main factor of the complement system?

Answer 18

1. Lysis
2. Opsonization
3. Inflammation
4. B cell stimulation

Question 19

All elements of the C3 convertase are located?

Answer 19

In the MHC III gene region

Question 20

CD59 inhibits

Answer 20

Poly-C9 assembly -> inhibits MAC formation

Question 21

S protein inhibits

Answer 21

Membrane insertion of C5b-C7 -> inhibits MAC formation