Complement

Question 1

What are the major functions of complement?

Answer 1

Lysis

Opsonization

Chemotaxis

Question 2

At which locations can complement act on microbes?

Answer 2

Blood & tissue

Question 3

How does complement directly lyse pathogens?

Answer 3

Through formation of a membrane attack complex (MAC) that forms pores in the membrane.

Question 4

What are the pathways for complement activation?

Answer 4

Classical, alternative, & lectin pathways

Question 5

What enzyme breaks down C3 into C3a and C3b?

Answer 5

C3 convertase

Question 6

What is the central complement component at which all activation pathways converge?

Answer 6

C3b

Question 7

What is the function of C3b?

Answer 7

Deposited on the pathogen as an opsonin

Question 8

What complement component is an important neutrophil chemotactic factor?

Answer 8

C5a

Question 9

What complement components function in inflammation and chemotactic factors?

Answer 9

C3a & C5a

Question 10

What is the function of C5b?

Answer 10

Binds to the pathogen surface and is essential for completion of the complement cascade

Question 11

What are the early complement proteins?

Answer 11

C1, C2, C4, C3

Question 12

How is the alternative pathway activated?

Answer 12

Spontaneous hydrolysis of C3 on all surfaces. This goes on to activate the C3 convertase, cleavage of C3, and formation of the C5 convertase

Question 13

How is the lectin complement pathway activated?

Answer 13

Lectin in the blood binds to mannose on microbes. C4b & C2a bind to the MBL to form the C3 convertase, cleaving C3

Question 14

How is the classical complement pathway activated?

Answer 14

The process is triggered by antibody binding to an antigen. C1 complex binds the antibody followed by C2a and C4b binding to the C1 complex. This leads to formation of the C3 convertase and cleavage of C3.

Question 15

What complement components make up the membrane attack complex?

Answer 15

C5b, C6, C7, C8, & C9

Question 16

Describe formation of the membrane attack complex (MAC).

Answer 16

C5b initaties assemply of tghe MAC. C6 binds to C5b and accepts C7. C7 inserts into the lipid membrane. C8 binds C5b, 6, 7 and iniates binding and polymerization of C9. C9 binds C5b, 6, 7, 8 and polymerized to form membrane pores.

Question 17

Are G+ or G- bacteria more susceptible to killing by the MAC? Why?

Answer 17

G- bactera are more susceptible to the MAC because they lack the thick peptidoglycan layer found in G+ bacteria. While G+ bacteria are less susceptible to the MAC, they are still opsonized and killed via phagocytosis.

Question 18

How are opsonized pathogens recognized for phaogcytosis?

Answer 18

Phagocytes express complement receptors on their surface that recognize complement proteins bound to microbes.

Question 19

What protein regulates the classical pathway? How?

Answer 19

C1INH (C1 inhibitor) prevents assembly of the C1 complex

Question 20

What protein regulates activity of the C3 convertase for all complement pathways?

Answer 20

Decay acceleration factor (DAC) / CD55 prevents formation of the C3 convertase

Question 21

What regulates formation of the MAC?

Answer 21

CD59/protectin blocks C9 binding and formation of the MAC