L9? - Complement

Question 1

What molecules, and how many, constitute the complement system?

Answer 1

Around 20 plasma proteins

Question 2

What are the 3 pathways involved in complement?

Answer 2

Classical, alternative and lectin pathways

Question 3

How is the alternative pathway in the complement system activated?

Answer 3

Activated directly by microbes

Question 4

How is the classical pathway in the complement system activated?

Answer 4

Antibodies

Question 5

How is the lectin pathway in the complement system activated?

Answer 5

Soluble mannose-binding lectin (MBL) proteins bind mannose on pathogens

Question 6

What are the 4 general functions of the complement system?

Answer 6

• Initiate acute inflammation
• Chemotaxis (attract neutrophils)
• Opsonisation (coat pathogens to enhance uptake by phagocytes)
• Kill pathogens

Question 7

What is the first stage of the alternative pathway?

Answer 7

C3 randomly splits into C3a and C3b, with C3b binding to any pathogen in the area

Question 8

How does C3b bind to pathogens and what does it bind to?

Answer 8

It covalently binds to amino or hydroxyl groups on the pathogen’s surface via a thiodiester bond (uncovered after C3 cleavage)

Question 9

What effect does C3b have when attached to the surface of a pathogen?

Answer 9

Encourages phagocytosis of the pathogen by opsonising (coating) it

Question 10

How is factor B involved in the alternative pathway?

Answer 10

C3b forms a complex with factor B, which is then cleaved by factor D to Ba and Bb

Forms C3bBb

Question 11

What is the alternative name for C3bBb?

Answer 11

Alternative pathway C3 convertase

Question 12

What does C3 convertase do?

Answer 12

Cleaves C3 into C3a and C3b, making more C3b to bind to the pathogen

Question 13

How is C5 convertase made?

What does this enzyme do?

Answer 13

C3bBb associates with a C3b to form C3bBbC3b

Cleaves C5 into C5a and C5b

Question 14

What does C5b do?

Answer 14

Triggers a cascade of sequential complement activation to form a complex with C6, C7, C8 and C9

Question 15

What is the structure of the complex that C5b forms?

Answer 15

C5b, C6, C7 and C8 associate and anchor to the pathogen, multiple C9s associate and form a ring

Question 16

What is the name of the complex that C5b forms?

What does this result in?

Answer 16

Membrane attack complex (MAC)

Punches holes in the pathogen where other immune components can enter and lyse it

Question 17

What complement molecule starts off the classical pathway?

Answer 17

C1

Question 18

What are the 3 subunits of C1?

Answer 18

C1q, C1r and C1s

Question 19

How is C1 activated?

3 steps

Answer 19

• 2 out of 6 C1q subunits bind to the constant domains of antibodies in complex with antigens
• Activates C1r
• Activates C1s (becomes an enzyme)

Question 20

What does C1s do after it has been activated?

Answer 20

Cleaves C4 into C4a and C4b

Cleaves C2 into C2a and C2b

Question 21

What happens to the cleaved C4 and C2?

Answer 21

C4b and C2a form a complex (C4b2a)

Question 22

What is the alternative name for C4b2a?

Answer 22

C3 convertase

Question 23

What is the name of the residual C3a, C5a and C4a from the complement cascade?
What is their main role?

Answer 23

Anaphylatoxins - create a chemotaxic gradient (more near the pathogen) which attracts neutrophils

Question 24

What regulates the C1 complex and causes it to dissociate?

Answer 24

C1 inhibitor

Question 25

What regulates the C3 convertases and causes them to dissociate?

Answer 25

Complement receptor 1 (CR1) and decay-accelerating factor (DAF)

Question 26

What regulates C4b and C3b and causes them to break down?

Answer 26

Factor I, factor H, and complement receptor 1 (CR1)

Question 27

What does CD59 do in regards to regulating the complement system?

Answer 27

Inhibits C9 from joining the membrane attack complex (MAC)