Innate Immunity Part II- Lecture 5

Question 1

What is the definition of a zymogen in immunology and give an example?

Answer 1

Proteases secreted in inactive form then cleaved into an active form
C3 –> C3a and C3b Via C3 convertase

Question 2

List the 9 stages of the Alternative Complement Pathway

Answer 2

1. C3 is spontaneously cleaved to C3b on the cell surface
2. Factor B binds to C3b
3. Factor D binds to Factor B
4. Factor B is cleaved into Bb and Ba
5. Bb is bound to C3b, forming C3Bb (C3 convertase)
6. C3 convertase cleaves C3 into C3b and C3a
7. C3b combines with C3Bb, forming C3bBbC3b (C5 convertase)
8. C5 convertase cleaves C5 into C5b and C5a
9. Formation of the MAC

Question 3

What is the function of MAC?

Answer 3

Membrane Attack Complex causes cell lysis and is the same in all complement pathways

Question 4

What stabilizes the interactions of the alternative pathway?

Answer 4

Properdin

Question 5

List the 7 steps of the classical complement pathway.

Answer 5

1. IgM binds to the surface of the bacterial pathogen
2. C1 binds to the “staple formation” of IgM
3. C1s cleaves C2 C2a and C2b, C4  C4a and C4b
4. C4b combines with C2a to form C4bC2a (C3 convertase)
5. C3 convertase cleaves C3 into C3b and C3a
6. C3b combines with C4bC2a forming C4bC2aC3b (C5 convertase)
7. Formation of the MAC

Question 6

What are the functions of the following complement proteins? C3b

Answer 6

C3b- Opsonization via CR1 on Macrophages

Question 7

What are the functions of the following complement proteins? C5b

Answer 7

C5b- Initiates MAC formation

Question 8

What are the functions of the following complement proteins?
C7
C9

Answer 8

C7- Inserts into the cellular membrane

C9- Polymerizes to form the pore

Question 9

What are the functions of the following complement proteins? C5a

Answer 9

C5a- Strong chemoattractant and initiates killing via ROS

Question 10

What are the functions of the following complement proteins? C5a > C3a

Answer 10

C5a > C3a (anaphylatoxin): Inflammation (SM contraction, increase in vascular permeability, degradation of Mast cells)

Question 11

What complement proteins make up the MAC complex?

Answer 11

MAC complex: C5b, C6, C7, C8, C9

Question 12

There are 2 other complement proteins that have regulatory functions. What does each do?

DAF and CR1

Answer 12

DAF- Blocks C2:C4 interactions

Both DAF and CR1: Enhances dissociation of C4bC2a OR C3bBb (both pathways)

CR1- dissociates C4bC2a OR C3bBb, with FI cleaves C4b or C3b, phagocytosis when bound to C3b (all pathways)

Question 13

What are the 4 ways to activate macrophages?

Answer 13

1. TLR activation (especially LPS on TLR 4)
2. IFN- gamma via NK cells
3. Complement Mediated
   a) CR1 (Macrophage activating factor) binds to C3b and is phagocytized
   b) Phagosome fuses with lysosome
   c) IFN- gamma releases trigger killing of pathogen via ROS

• Note: Catalase (+) bacteria can survive phagolysosome –> formation of water and oxygen
  4. CD4 TH1 cells (intracellular pathogens ONLY): Macrophage activating factor presents antigen via MHC class II to T cell and T cell releases IFN- gamma via CD40 on Macrophage activating factor, CD40L on T cells)

Question 14

What are the 3 inflammatory molecules and what does the first 2 cause?

Answer 14

IL-1: Induces fevers
TNF: Increases vascular dilation and permeability
IL-6: Acute Phase Proteins (CRP, SAP)*

Question 15

What are the two types of interferons?

Answer 15

Type 1: INF alpha and beta

Type 2: INF-gamma

Question 16

Describe Type 1 interferons: INF alpha and beta

Answer 16

Intracellular TLR (which are ??), in particular viral RNA

Response: On healthy cells, create antiviral replication proteins, on infected cells enhanced killing via CTL (CD8 cells)

Question 17

Describe Type 2 interferons: INF-gamma

Answer 17

Response: Enhanced macrophage killing and production of IgG antibodies