CIS #2 Flashcards
How is hereditary C1-inhibitor deficiency passed genetically?
autosomal dominant
What does decay-accelerating factor do?
regulates the formation of the C3 convertase
What is acquired C1-inh deficiency due to?
an accelerated consumption of C1-inh that depends on:
- autoantibodies that bind and inactivate C1-inh
- diseases like lymphoproliferative diseases that consume C1-inh
What is the mechanism of how a deficiency in C1 inhibitor can cause HAE?
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
What is the normal pathway of defense against pyogenic bacteria?
- opsonization
- MAC formation
- Phagocytosis and intracellular killing
What are the clinical outcomes of a deficiency in C3, properdin, or MAC proteins?
neisserial infections
What would a deficiency in CD59 cause?
failure to prevent the formation of MAC on autologous cells
clinical: hemolysis, thrombosis
What deficiencies will lead to failure to form the MAC?
C3, properdin, any of the proteins in the mac complex
What are the clinical outcomes of a C3 deficiency?
pyogenic bacterial infections, may be accompanied by distinctive rash
membranoproliferative glomerulonephritis
What would deficiencies in any part of C1, C4, or C2 lead to?
failure to activate the classical pathway
clinical: SLE
What is hereditary angioedema (HAE) often misdiagnosed as?
an allergic reaction
What does C1-Inh plasma concentrate do in HAE or AAE?
reverses severe laryngeal attacks and abdominal attacks
What is the most common disease associated with alternative pathway defects?
pyogenic infections
What is a major mechanism of killing neisseriae bacteria?
What deficiency can cause increased susceptibility to these bacteria?
extracellular lysis
deficiency of components of the MAC
What are the major things that can cause increased susceptibility to pyogenic bacteria?
defects of:
antibody production
complement proteins of classical path
complement receptors on phagocytes
What causes paroxysmal nocturnal hemoglobinuria?
somatic mutation –> deficiency in glycosylphosphatidylinositol = lipid tail that anchors DAF and CD59 –> RBCs are more susceptible to complement –> hemolysis
How do you treat HAE?
for HAE: attenuated androgens
for AAE: anti-fibrinolytic agents
What diseases are associate with defects in MAC formation?
neisseria infections
SLE
glomerulonephritis
What are the most important complement opsonins in the defense against bacterial infection?
C3b and iC3b
What would a deficiency in C1 inhibitor cause?
loss of regulation of C1 and failure to activate kallikrein
clinical: angioedema
How does C1-inhibitor deficiency arise?
Can be inherited or aquired –> hereditary or acquired angioedema
What would deficiencies in factor H and factor I lead to?
failure to regulate the activation of C3, severe secondary C3 deficiency
clinical: hemolytic-uremic syndrome, membranoproliferative glomerulonephritis
What does CD59 do?
restricts the formation of the MAC
