Lecture 4: The Complement System

Question 1

What is the complement system?

Answer 1

Complement (C’) system is a collection of labile proteins present in blood and other fluids

Question 2

C’ circulate in their _________ form

Answer 2

Inactive form (zymogens)

Question 3

When any of the pathways interacts with a pathogen, _____________ is created which cleaves __ to ___ (involved in inflammation) and ___ (main effector of the C’ system)

Answer 3

C3 convertase
C3
C3a
C3b

Question 4

How is the Classical pathway activated?

Answer 4

C1 binds to microbial surface or binds to antibodies on a microbial surface

Question 5

How is the Alternative pathway activated?

Answer 5

Can be activated by spontaneous hydrolysis and activation of C3 which can bind to microbial surfaces

Question 6

How is the Lectin pathway activated?

Answer 6

Can be activated by soluble CHO-binding proteins (MBL and Ficolins) that bind to CHOs on microbial surfaces

Question 7

What is the function of C3a?

Answer 7

Induces inflammation

Question 8

What is the function of C3b?

Answer 8

Main effector of the C’ system, forms membrane attack complex

Question 9

Describe the Classical Pathway:

Answer 9

1. C1q binds to the Fc portion of Ab bound to Ag
2. C1s cleaves C2 and C4 which combine to form C4b2a (C3 convertase)
3. C4b2a cleaves C3

Question 10

Describe the Lectin Pathway:

Answer 10

1. MBL or Ficolin bind to CHOs on a pathogen
2. MASP-2 cleaves C4 and C2 which combine to for C4b2a (C3 convertase)
3. C4b2a cleaves C3

Question 11

Describe the Alternative Pathway:

Answer 11

1. C4b2a cleaves C3 to C3a and C3b
2. C3b binds to the pathogen surface and to Factor B or Properdin which forms C3bBb (C3 convertase)
3. C3bBb cleaves C3

Question 12

What happens when C3 is cleaved?

Answer 12

• C3a (with C5a) assist in inflammation [all the ones with a do this]
• C3b opsonises pathogens (MO can eat more easily)
• C3b along with C4b2a forms C4b2a3b (C3/C5 convertase)

Question 13

What do C3/C5 convertases do?

Answer 13

• Cleave C3 and C5

- C5a (assists inflammation) and C5b (initiates formation of the Membrane Attack Complex)

Question 14

How is the Membrane Attack Complex Formed?

Answer 14

• C5b binds C6 and C7
• C5b67 then bind C8and insert into the cell membrane
• 10-16 C9 molecules polymerise to form a pore in the membrane

Question 15

How are host cells protected from C’ activation?

Answer 15

• C’ regulatory proteins are expressed only by host cells
• Decay Accelerating Factor (DAF) disrupts C3 convertase production
• CR1 also disrupts C3 convertases

Question 16

What is the function of CD59 (Protectin)?

Answer 16

Protectin prevents the recruitment of C9 for the membrane attack complex

Question 17

Infection causes resident macrophages to release cytokines like TNFα, what does this do?

Answer 17

• Causes rapid externalisation of granules known as Weibel-Palade bodies in endothelial cells
• Granules contain pre-formed P-selectin and endothelial cells synthesis E-selectin
• P and E selectins interact with sialyl-Lewisx present on neutrophils

Question 18

Acute phase proteins are produced by ___________ in response to ________ released by macrophages in the presence of _________.

Answer 18

Liver Cells
Cytokines
Bacteria

Question 19

What is C-reactive protein?

Answer 19

An opsonin that activates the C’ pathway by binding ligands on bacterial or fungal cell surfaces