Complement

Question 1

What are the results of activation of complement system? (5)

Answer 1

cell lysis, increased phagocytosis, increased vascular permeability, enhanced leukocyte chemotaxis, stimulation of macrophages

Question 2

What is the end result of either classical or alternate pathway?

Answer 2

cleavage of C3 to C3b and C3a

Question 3

What complements form the MAC? How does it form?

Answer 3

C5b-C9

C5b binds 6, then 7, then 8 (first to insert into the membrance) and 9 causes pore to form leading to cell lysis

Question 4

What is the bigger fragment, C5a/C5b, C2a/C2b?

Answer 4

C5b, C2a

Question 5

Which pathway is first to act? How?

Answer 5

alternative pathway, pathogen surface creates local environment conducive to complement activation

Question 6

How does C1 act?

Answer 6

C1 (with three subunits r, q, s) binds pentameric IgM or 2 IgGs on surface with C1q.
C1r cleaves C1s to activate it.
Activated C1s cleaves C2 and C4.

Question 7

How does C4b2a complex form?

Answer 7

Both C2 and C4 cleaved by activated C1s. C4b binds bacterial surface and C2a binds it.

Question 8

What cleaves C3 in the classical pathway?

Answer 8

C4b2a complex is C3 convertase.

Question 9

How is the alternate pathway activated?

Answer 9

C3b is at a low concentration in bloodstream, binds pathogen surface. Factor B binds C3b. Factor D cleaves Factor B to Bb and Ba to form C3bBb complex, an active protease that cleaves more C3 to C3b.

Question 10

What function does properdin have?

Answer 10

stabilizes C3 convertase C3bBb complex on pathogen surface

Question 11

What function does Factor H have?

Answer 11

Binds C3b to let Factor I clip it to iC3b (inactive form)

Question 12

How are human cells nonpermissive to the alternate pathway?

Answer 12

DAF and MCP inhibit production of an active C3bBb complex. DAF knocks Bb off C3b. MCP knocks Bb off C3b and allows Factor I to inactivate C3b to iC3b.

Question 13

What receptor on macrophages bind C3b?

Answer 13

CR1

Question 14

Does iC3b have a function?

Answer 14

Yes, it can still stimulate phagocytosis.

Question 15

What two stimuli are needed for engulfment of pathogen by neutrophil?

Answer 15

-Ab (Fc receptor) and C3b (complement receptor)

Question 16

How is C5 activated by the alternative pathway? classical?

Answer 16

for alternative, C3bBb binds C3b, which cleaves C5

for classical, C4b2a binds C3b, which cleaves C5

Question 17

What do C5a and C5b do?

Answer 17

C5a- critically important chemotactic factor

C5b- starts lytic path

Question 18

How is MAC prevented in human cells?

Answer 18

CD59 binds C5b678 to prevent C9 from joining and forming a pore

Question 19

What complements are anaphylatoxins? How do they act?

Answer 19

C3a, C5a
-act on blood vessels to increase vascular permeability for extravasation of complement, plasma proteins, and leukocytes into tissue

Question 20

What is a C1 inhibitor?

Answer 20

C1INH inhibits C1 by removing C1r or C1s

Question 21

What is C4BP?

Answer 21

disrupts the classical C3 convertase (C4b2a) by kicking off C2a and allowing Factor I to inactivate C4b

Question 22

What does a deficiency of C1, C2, C4 cause?

Answer 22

immune-complex disease, no greater rate of bacterial infection

Question 23

What does a deficiency of C3 cause?

Answer 23

susceptibility to capsulated bacteria

Question 24

What does a deficiency of C5-C9 cause?

Answer 24

susceptibility to Neisseria

Question 25

What does a factor I deficiency cause?

Answer 25

susceptibility to capsulated bacteria like C3 because if you don’t have an inhibitor, all of C3 gets used up and isn’t there when you need it

Question 26

What do DAF or CD59 deficiencies cause?

Answer 26

autoimmune conditions

Question 27

Which is the more important function of complement: opsonization or MAC?

Answer 27

opsonization is more important for clearing more bacteria

Question 28

How do you determine the amount of complement deficiency?

Answer 28

Expose patient serum to sheep RBCs that have previously been coated with rabbit anti-sheep Ab.
The presence of complement determined by the lysis of Ab-coated RBCs and expessed as CH50, the dilution of a patient’s serum that gives 50% lysis of RBCs