CIS #2

Question 1

How is hereditary C1-inhibitor deficiency passed genetically?

Answer 1

autosomal dominant

Question 2

What does decay-accelerating factor do?

Answer 2

regulates the formation of the C3 convertase

Question 3

What is acquired C1-inh deficiency due to?

Answer 3

an accelerated consumption of C1-inh that depends on:

• autoantibodies that bind and inactivate C1-inh
• diseases like lymphoproliferative diseases that consume C1-inh

Question 4

What is the mechanism of how a deficiency in C1 inhibitor can cause HAE?

Answer 4

C1 inhibitor cannot stop C1 from spontaneously hydrolyzing –> keeps making C3 convertase (C4bC2a classical) –> keeps making C4a –> stimulates the release of histamine from mast cells –> extravasation and edema

Question 5

What is the normal pathway of defense against pyogenic bacteria?

Answer 5

1. opsonization
2. MAC formation
3. Phagocytosis and intracellular killing

Question 6

What are the clinical outcomes of a deficiency in C3, properdin, or MAC proteins?

Answer 6

neisserial infections

Question 7

What would a deficiency in CD59 cause?

Answer 7

failure to prevent the formation of MAC on autologous cells

clinical: hemolysis, thrombosis

Question 8

What deficiencies will lead to failure to form the MAC?

Answer 8

C3, properdin, any of the proteins in the mac complex

Question 9

What are the clinical outcomes of a C3 deficiency?

Answer 9

pyogenic bacterial infections, may be accompanied by distinctive rash
membranoproliferative glomerulonephritis

Question 10

What would deficiencies in any part of C1, C4, or C2 lead to?

Answer 10

failure to activate the classical pathway

clinical: SLE

Question 11

What is hereditary angioedema (HAE) often misdiagnosed as?

Answer 11

an allergic reaction

Question 12

What does C1-Inh plasma concentrate do in HAE or AAE?

Answer 12

reverses severe laryngeal attacks and abdominal attacks

Question 13

What is the most common disease associated with alternative pathway defects?

Answer 13

pyogenic infections

Question 14

What is a major mechanism of killing neisseriae bacteria?

What deficiency can cause increased susceptibility to these bacteria?

Answer 14

extracellular lysis

deficiency of components of the MAC

Question 15

What are the major things that can cause increased susceptibility to pyogenic bacteria?

Answer 15

defects of:
antibody production
complement proteins of classical path
complement receptors on phagocytes

Question 16

What causes paroxysmal nocturnal hemoglobinuria?

Answer 16

somatic mutation –> deficiency in glycosylphosphatidylinositol = lipid tail that anchors DAF and CD59 –> RBCs are more susceptible to complement –> hemolysis

Question 17

How do you treat HAE?

Answer 17

for HAE: attenuated androgens

for AAE: anti-fibrinolytic agents

Question 18

What diseases are associate with defects in MAC formation?

Answer 18

neisseria infections
SLE
glomerulonephritis

Question 19

What are the most important complement opsonins in the defense against bacterial infection?

Answer 19

C3b and iC3b

Question 20

What would a deficiency in C1 inhibitor cause?

Answer 20

loss of regulation of C1 and failure to activate kallikrein

clinical: angioedema

Question 21

How does C1-inhibitor deficiency arise?

Answer 21

Can be inherited or aquired –> hereditary or acquired angioedema

Question 22

What would deficiencies in factor H and factor I lead to?

Answer 22

failure to regulate the activation of C3, severe secondary C3 deficiency
clinical: hemolytic-uremic syndrome, membranoproliferative glomerulonephritis

Question 23

What does CD59 do?

Answer 23

restricts the formation of the MAC