Complement

Question 1

Where does complement activation take place?

Answer 1

on antigenic surfaces

Question 2

When activated, complement components interact in a highly regulated fashion that protect the host by initiating:

Answer 2

• an inflammatory response
• recruitment of inflammatory cells (neutrophils, macrophages)
• opsonization of microbial pathogens (C3b, CR1)
• killing of microbial pathogens via lytic mechanism (MAC)

Question 3

Most complement components are ______ that become active following _________.

Answer 3

proteases; proteolytic cleavage

Question 4

When is classical pathway activation initiated?

Answer 4

after immune complex formation; the complement component C1 recognizes the antigen-Ab complex

Question 5

MBL/ficolins are physically associated with 2 serine proteases:

Answer 5

MASP-1 and MASP-2

Question 6

What is the function of C4b2a?

Answer 6

It is a C3 convertase capable of cleaving C3 into C3b and C3a. It therefore represents a major point of amplification of the pathways, since one C3 convertase can cleave up to 1000 molecules of C3.

Question 7

What does C3b do?

Answer 7

It acts as a powerful opsonin when bound to the antigenic surface and enhances uptake of antigenic particles by phagocytes. (CR1 receptor of innate immune cells bind C3b to clear pathogen)

Question 8

What cleaves C4 to C4a and C4b?

Answer 8

activated C1s

Question 9

What is the lectin pathway initiated by?

Answer 9

a protein, Mannan Binding Lectin (MBL), or ficolins

Question 10

What does MBL vs. ficolins bind?

Answer 10

• MBL: mannose and other complex carbs on the surface of microbial pathogens
• ficolins: oligosaccharides

Question 11

Which pathway are MASP-1 and MASP-2 involved with, and how are they activated?

Answer 11

They are involved in the Lectin pathway and become activated when MBL or ficolins bind to pathogenic surfaces.

Question 12

Which complexes are able to cleave C4?

Answer 12

activated C1qrs or MBL/ficolins-activated MASP-1 and MASP-2

Question 13

What is C4b2a?

Answer 13

a C3 convertase capable of cleaving C3 into C3b and C3a

Question 14

What is C4b2a3b?

Answer 14

a C5 convertase capable of cleaving C5 into C5a (soluble inflammatory mediator) and C5b (capable of complexing w/ additional complement components and initiating formation of MAC)

Question 15

The generation of ____ initiates the final phase of complement activation, which is the formation of the ______.

Answer 15

C5b; MAC

Question 16

Are C3a and C5a soluble or membrane-bound? What do they do?

Answer 16

They remain soluble and produce local inflammatory effects.

Question 17

How is the alternative complement pathway activated?

Answer 17

It depends on slow hydrolysis of C3, which spontaneously occurs in the plasma.

Question 18

C3bBb is in the alternative pathway– what is its analog in the classical pathway?

Answer 18

C4b2a (both act as C3 convertases)

Question 19

C3bBbC3b is in the alternative pathway– what is its analog in the classical pathway?

Answer 19

C4b2a3b (both act as C5 convertases)

Question 20

Deficiencies in MAC are associated with which types of conditions/infections?

Answer 20

Neisseria infection only