Lecture 12: Complement

Question 1

What are the 4 purposes of complement?

Answer 1

To generate products that

1) recruit inflammatory cells (promoting inflammation)
2) opsonize microbial pathogens and immune complexes (facilitating antigen clearance)
3) Kill microbial pathogens (via lytic mechanism known as membrane attack complex)
4) generate inflammatory response

Question 2

Where does complement activation take place?

Answer 2

on antigenic surfaces

but also produces several soluble fragments that have important biologic activity

Question 3

What are the 3 distinct pathways of complement activation?

Answer 3

1) Classical
2) Lectin
3) Alternative Pathways

Question 4

What activates the classical pathway?

Answer 4

antigen:antibody complexes

Question 5

What activates the lectin pathway?

Answer 5

lectin binding to pathogen surfaces

Question 6

What activates the alternative pathway?

Answer 6

pathogen surfaces

Question 7

Again, what are 3 important functions of complement?

Answer 7

1) recruit inflammatory cells
2) opsonization of pathogens
3) killing of pathogens

Question 8

How are the components of the complement system designated?

Answer 8

letter C followed by simple number (like 3)

Question 9

Once components of the complement system are cleaved during activation, how are they designated?

Answer 9

with a lower case letter

ex: C3a

Question 10

How are components of the alternative pathway named?

Answer 10

by capital letters, such as B or D

Question 11

How are components of the Lectin pathway named?

Answer 11

acronyms

like MASP-2

Question 12

What does a designation iC3b mean?

Answer 12

i indicates inactive

Question 13

What is the common feature of the 3 complement pathways?

Answer 13

cleavage of C3 into C3a and C3b (done by C3 convertase)

C3a –> released into plasma to cause inflammation
C3b —> stays bound to microbial surface

Question 14

How is the lectin pathway intiated?

Answer 14

mannose binding lectin and ficolins recognize and bind carbs on pathogen surface

Question 15

What complement factors are activated in the lectin pathway?

Answer 15

MBL/ficolins, MASP-2, C4, C2

Question 16

How is the classical pathway activated?

Answer 16

C1q interacts with pathogen surface or antibodies bound to surface

Question 17

What factors are activated in the classical pathway?

Answer 17

C1q, C1c, C1s, C4, C2

Question 18

Ho is the alternative pathway activated?

Answer 18

C3 undergoes spontaneous hydrolysis to C3(H2O) to initiate eventual deposition of C3 convertase on microbial surface

Question 19

What factors are activated in the alternative pathway?

Answer 19

factor D, factor B, properdin, C3

Question 20

Once C3 convertase does its thing, what 3 things happen?

Answer 20

1) C3a and C5a recruit phagocytic cells to the site of infection and promote inflammation
2) phagocytes with receptors for C3b engulf and destroy the pathogen
3) completion of complement cascade leads to formation of membrane attack complex (MAC) which disrupts cell membrane and causes cell lysis

Question 21

What stimulates classical completment?

Answer 21

formation of immune complexes

Question 22

What part of the classical pathway recognizes ICs?

Answer 22

C1

Question 23

What does C1 do?

Answer 23

binds to the Fc region of the antibody that is exposed during the conformational change the IC undergoes when antibody binds to antigen

Question 24

What has to occur of the activation of the C1qrs complex?

Answer 24

2 C1q glubular heads to be bound simultaneously to antibody

Question 25

Once C1q is bound, what happens?

Answer 25

C1r undergoes conformational change and becomes enzymatically active

Question 26

What does C1r do?

Answer 26

cleaves C1s to make it enzymatically active

Question 27

How does IgM differ from IgG in activating complement?

Answer 27

IgG needs to be in high concentration to get activation

only a single IgM can activate complement

Question 28

C1q binds to ____ IgM and ___ IgG

Answer 28

1 IgM and 2 IgG