Complement system

Question 1

What are the 3 pathways in the complement system?

Answer 1

Alternate/properdin pathway

Mannose-binding lectin pathway

Classical pathway

Question 2

Which 2 types of microorganisms directly activate the alternate/properdin pathway of the complement system?

Answer 2

Fungal

Bacterial

Question 3

Does the alternate/properdin pathway of the complement system need to be activated after establishment of the immune response?

Answer 3

No

Question 4

Give 2 reasons why alternate/properdin pathway of the complement system can be activated before immune response establishment?

Answer 4

Doesn’t need antibodies

Doesn’t involve the early complement proteins C1,C2,C4

Question 5

In the alternate/properdin pathway of complement system, what is the initial complement protein?

Answer 5

C3

Question 6

In the alternate/properdin pathway of complement system, how does C3 bind to bacterial surfaces?

Answer 6

C3 spontaneously cleaved in serum and can covalently bind to bacterial surfaces

Question 7

In the alternate/properdin pathway of complement system, what happens to C3 which is bound to the bacterial surface?

Answer 7

Properdin B factor binds to the C3b part of the C3 that is bound to the bacterial surface

Question 8

In the alternate/properdin pathway of complement system, what happens after properdin b has bound to the C3b part of the bound C3 protein?

Answer 8

Properdin factor D splits properdin factor B in the complex to yield the Bb active fragment that remains linked to C3b

Properdin B -> Bb

So C3bBb is formed (alternate C3 convertase)

Question 9

What is the active unit formed at the end of the alternate/properdin pathway?

Answer 9

C3bBb (alternate C3 convertase)

Question 10

Which 2 types of microorganisms activate the mannose-binding lectin pathway?

Answer 10

Bacterial

Fungal

Question 11

Does the mannose-binding lectin pathway of the complement system need to be activated after establishment of the immune response, and why?

Answer 11

No

This pathway is independent of antibodies

Question 12

What is a mannose-binding lectin?

Answer 12

Large serum protein that binds to nonreduced mannose, fucose, and glucosamine on bacterial, fungal, and other cell surfaces.

Question 13

What 3 substances on bacterial and fungal surfaces can mannose-binding lectin bind to?

Answer 13

nonreduced mannose, fucose, and glucosamine

Question 14

In the mannose-binding lectin pathway, what binds to the microbial surface, and what does this activate?

Answer 14

Mannose-binding lectin binds to microbial surfaces

Activates the cleavage of the mannose-binding lectin–associated serine protease

Question 15

What is the action of the cleaved mannose-binding lectin–associated serine protease, in the mannose-binding lectin pathway?

Answer 15

Cleaves C2 and C4 to produce C3 convertase

C4bC2a is C3 covertase

Question 16

What is the end/junction product of all 3 pathways of the complement system, after which they all have the same process?

Answer 16

C3 convertase

Question 17

What is initial complement protein that is activated in the classical pathway of the complement system, and what 3 components is this protein made of?

Answer 17

C1 protein complex is activated, which is composed of separate proteins designated C1q, C1r, C1s

Question 18

In the classical pathway of the complement system, how is C1 activated?

Answer 18

Antigen binds to IgM or IgG to form antigen-antibody complex

Formation of antigen-antibody complex activates C1

Question 19

Which component of C1 binds to the antigen-antibody complex in the classical pathway of complement system, and what does this activate?

Answer 19

C1q binds to the Fc region of antibody, leading to activation of the proteolytic activities of C1r and C1s

Question 20

In the classical pathway of the complement system, what two complement proteins are cleaved by the activated C1s protein?

Answer 20

C1s cleaves C4 to C4a and C4b, and C2 to C2a and C2b

Question 21

In the classical pathway of the complement system, which cleaved proteins join to form C3 convertase?

Answer 21

The union of C4b and C2a produces C4b2a, which is known as C3 convertase

Question 22

What is the catalytic action of C3 convertase in the complement system?

Answer 22

C3 convertase cleaves C3 into C3a and C3b

Question 23

What are the 2 possible actions of C3b protein, and what property of C3b allows this, in the complement system?

Answer 23

C3b contains thioester bond

Thioester bond allows C3b to either covalently bind to cell membrane or hydrolyze

Question 24

After C4b2a (C3 convertase) is formed, what does it bind to?

Answer 24

Binds to cell membrane

Question 25

How is C5 convertase produced from C3b and another protein, in the complement system?

Answer 25

Interaction of C3b with C4b2a bound to the cell membrane produces C4b3b2a, which is termed C5 convertase

Question 26

What is the catalytic action of C5 convertase?

Answer 26

C5 convertase splits C5 into C5a and C5b

Question 27

Why are the catalytic actions of C3 and C5 convertase called amplification steps?

Answer 27

One C3/C5 convertase molecule cleaves many C3/C5 proteins

Question 28

What are the 2 functions of C3a and C5a proteins in the complement system?

Answer 28

Is an anaphylatoxin that stimulates mast cells to release histamines and TNF-alpha Chemotactic attractant that facilitates neutrophil and macrophage exit from inside capillary to distant site of infection

Question 29

What are the 3 effects of TNF-alpha when produced by the complement system?

Answer 29

Promotes inflammation Enhances vascular permeability Enhances smooth muscle contraction

Question 30

What is action of C4a in the complement system?

Answer 30

Is an anaphylatoxin that stimulates mast cells to release histamines and TNF-alpha Chemotactic attractant that facilitates neutrophil and macrophage exit from inside capillary to distant site of infection

Question 31

What is the function of C3b in the complement system, relative to phagocytes?

Answer 31

Opsonin that promotes clearance of microbes by binding directly to the cell to make the cell more recognizable to phagocytic cells which have receptors for C3b

Question 32

How is C3d protein produced in the complement system, and what is its function?

Answer 32

Activator of B lymphocytes Produced by further cleavage of C3b

Question 33

How can products of the complement system activate the clotting cascade?

Answer 33

Activated coagulation factors can cleave C5a, to increase vascular permeability Protease of the lectin pathway can cleave prothrombin Overall results in production of fibrin and activation of the clotting cascade

Question 34

Which complement proteins assemble to form the Terminal Membrane Attack Complex?

Answer 34

C5b,C6,C7,C8,C9

Question 35

Where does the Terminal MAC assemble in complement system?

Answer 35

Assembles on target pathogen cell membrane

Question 36

How does the complement system initiate assembly of the Terminal MAC?

Answer 36

C5 cleavage into C5a and C5b fragments initiates assembly

Question 37

How does an assembled Terminal MAC on the target pathogen cell membrane kill the pathogen?

Answer 37

MAC complex drills a hole in the membrane, leading to apoptosis/hypotonic lysis of cells

Question 38

Are both gram-negative and gram-positive bacteria able to be killed by MAC, and why?

Answer 38

Gram-positive bacteria are relatively insensitive, as peptidoglycan layer limits access of the complement components to the plasma membrane unless disrupted by lysozyme Neisseria and other gram-negative bacteria are very sensitive, as they contain lipooligosaccharide (LOS), which lacks O-antigenic side chains and it allows access of complement to the membrane surface