6: Complement

Question 1

Two other systems that the complement works in cooperation with

Answer 1

1. Blood coagulation pathways

2. Kinin-kallikrein system

Question 2

Alternative C3 and C5 convertases

Answer 2

C3 convertase: C3bBb

C5 convertase: C3bBbC3b

Question 3

Three extra proteins in alternative pathway

Answer 3

Properdin, factor B, factor D

Question 4

Factor B (Bb)

Answer 4

Active enzyme of C3 and C5 convertases

Question 5

Factor D

Answer 5

Cleaves factor B when bound to C3b

Question 6

Properdin

Answer 6

Stabilizes alternative C3 convertase on microbe surfaces

Question 7

What protein in alternative pathway is most abundant in serum

Answer 7

C3

Question 8

Classical and lectin C3 and C5 convertases

Answer 8

C3 convertase: C4bC2a

C5 convertase: C4bC2aC3b

Question 9

Four proteins involved in classical pathway

Answer 9

C1, C2a, C4a, C4b

Question 10

C1: describe structure

Answer 10

C1q + tetramer of C1r (2) + C1s (2)

Question 11

C1 function

Answer 11

Initiates classical pathway by binding IgM or IgG on Ag

Question 12

C1q function

Answer 12

Binds Fc portion of Ab with 6 identical subunit arms

Question 13

C1r function

Answer 13

Cleaves C1s to activate it

Question 14

C1s function

Answer 14

Cleaves C4 and C2

Question 15

Most abundant classical pathway protein in serum

Answer 15

C4

Question 16

What initiates the lectin pathway

Answer 16

MBL binding bacterial surface -> activates MASPs

Question 17

Which MASP cleaves C4 and C3?

Answer 17

MASP2

Question 18

MASP structure

Answer 18

MASP1, 2, and 3 all form a complex together

Question 19

C1-INH function

Answer 19

Irreversibly inactivates C1r, C1s, and MASPs

Question 20

Side affect of C1-INH

Answer 20

Inhibits kallikrein-Kirin and coagulation cascades

Question 21

What causes swelling in hereditary angioedema?

Answer 21

Bradykinin, cleaved by kininongen when C1-INH isn’t present to inhibit kallikrein activating kininogen

Question 22

Factor I function

Answer 22

Inactivates C3b and C4b

Question 23

Four cofactors that can work with Factor I

Answer 23

MCP, CR1, factor H, C4BP

Question 24

Three proteins that destabilize CP/LP C3 convertases

Answer 24

DAF, CR1, C4BP

Question 25

Three proteins that destabilize AP C3 convertases

Answer 25

DAF, CR1, factor H

Question 26

Three proteins that inhibit MAC formation

Answer 26

CD59, vitronectin, S protein

Question 27

What does a deficiency in C1, C2, or C4 cause?

Answer 27

Immune complex disease

Question 28

What does a deficiency in C3 or factor I cause?

Answer 28

Susceptibility to capsulated bacteria

Question 29

What does a deficiency in MAC proteins cause

Answer 29

Susceptibility to Neisseria

Question 30

What does a deficiency in Factor D or properdin cause?

Answer 30

Susceptibility to capsulated bacteria + Neisseria

Question 31

What does a deficiency in DAF and CD59 cause?

Answer 31

Auto-immune like conditions (ex: PNH)

Question 32

What does a deficiency in C1-INh cause?

Answer 32

Hereditary angioedema (HAE)

Question 33

Lab test involved in testing complement

Answer 33

Ability of pt’s serum to lyse sheep RBCs

Question 34

CH50 and AH50 test results in complement testing

Answer 34

abnormal CH50 -> defect in CP Abnormal APH50 -> defect in AP Abnormal both -> defect in MAC or C3

Question 35

Symptoms of HAE

Answer 35

Edema in various parts of the body, abdominal pain, nausea, vomiting, swelling of airway can be fatal

Question 36

Triad of features in paroxysmal nocturnal hemoglobinuria (PNH)

Answer 36

Hemolysis, thrombosis, anemia

Question 37

What causes PNH?

Answer 37

Deficiency in GPI (DAF, CD59) -> Failure to regulate MAC formation

Question 38

What is the sign of poor prognosis in SLE patients?

Answer 38

Kidney involvement

Question 39

Two major causes of glomerular disorders

Answer 39

1. Deposition of immune complexes -> CP activation | 2. Abs binding directly to kidney self-Ags