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Complement System Flashcards

1
Q

What are the 10 complement regulatory proteins? (found on the surface of human cells)

A
  • C1 Inhibitor (C1-Inh)
  • MCP
  • DAF (CD55)
  • CR1
  • C4 Binding Protein (C4BP)
  • Factor H
  • Factor I
  • CD59
  • S Protein
  • Vitronectin
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2
Q

Effects of MCP

A
  • Cofactor for I-mediated cleavage of C3b and C4b

- Cofactor for inactivation of C3b complement fragment

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3
Q

Effects of C1 Inhibitor

A
  • Inactivates C1r and C1s proteases, and MASP-1 and MASP-2
  • IRREVERSIBLE inactivation prevents activation of the CP and LP initiating complexes
  • Also inhibits the Kallikrein-Kinin (inactivates plasma kallikrein resulting in formation of Bradykinini which then causes swelling) and coagulation cascades
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4
Q

Effects of DAF (CD55)

A
  • Destabilizes C3/C5 convertase of the CP and AP (decay accelerating activity) by inducing rapid dissociation of C2a or Bb
  • Involved in protecting RBCs from lysis by complement
  • One of the two GPI anchor proteins
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5
Q

Effects of CR1

A
  • Decay accelerating activity of as well as cofactor activity for I-mediated cleavage of C3b and C4b
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6
Q

Effects of C4BP

A
  • Binds to C4b in Lectin and CP

- Decay accelerating and cofactor activity

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7
Q

Effects of Factor H

A
  • Binds to C3b

- Has decay accelerating activity of the AP C3 and C5 Convertases and cofactor activity

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8
Q

Effects of Factor I

A
  • Degrades C3b and C4b aided by cofactors
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9
Q

Effects of CD59

A
  • Blocks the C9 association with C5b-8 to prevent C5b-9 formation on host cells
  • Involved in protecting RBCs from lysis by complement
  • One of the two GPI anchor proteins
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10
Q

Effects of S-Protein

A
  • Binds to C4b and inhibits C9 polymerization
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11
Q

What are the three different regulatory proteins that destabilize C3 convertase in the CP?

A
  • DAF (CD55)
  • CR1
  • C4BP
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12
Q

What are the three different regulatory proteins that destabilize C3 convertase in the AP?

A
  • DAF (CD55)
  • Factor H
  • CR1
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13
Q

Is DAF (CD55) soluble or membrane-bound?

A

Membrane-bound

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14
Q

Is CR1 soluble or membrane-bound?

A

Membrane-bound

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15
Q

Is C4BP soluble or membrane-bound?

A

Soluble

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16
Q

Is Factor H soluble or membrane-bound?

A

Soluble

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17
Q

Cleavage of C3b and C4b by _____ directly prevents the formation of the C3 Convertase and indirectly prevents the formation of C5 Convertase in all 3 pathways

A

Factor I

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18
Q

What are the three different regulatory proteins that act as cofactors for Factor I in inactivating C3b? (AP, CP and Lectin)

A
  • MCP
  • CR1
  • Factor H
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19
Q

What are the three different regulatory proteins that act as cofactors for Factor I in inactivating C4b? (CP and Lectin)

A
  • MCP
  • C4BP
  • CR1
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20
Q

Is MCP soluble or membrane-bound?

A

Membrane-bound

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21
Q

Is CD59 soluble or membrane-bound?

A

Membrane-bound

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22
Q

Is Vitronectin soluble or membrane-bound?

A

Soluble

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23
Q

Effects of Vitronectin

A

MAC inhibitory binding protein that prevents C9 binding and polymerization

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24
Q

Is S Protein soluble or membrane-bound?

25
What are the effects of a C3 deficiency?
- Susceptibility to capsulated bacteria | - Increased numbers of severe bacterial infections with extracellular bacteria
26
What are the effects of a C1, C2, or C4 deficiency?
Immune-complex disease / autoimmune disease
27
What are the effects of a C5-C9 deficiency?
Susceptibility to Neisseria (large genus of gram-negative bacteria)
28
What are the effects of a Factor D or Properdin (Factor P) deficiency?
(involved in AP) | - Susceptibility to capsulated bacteria and Neisseria but no immune-complex disease
29
What are the effects of a Factor I deficiency?
Similar effects to deficiency of C3 -- susceptibility to capsulated bacteria
30
What are the effects of a DAF (CD55) or CD59 deficiency?
Autoimmune-like conditions including paroxysmal nocturnal hemoglobinuria (PNH: consequence of the failure to regulate the formation of MAC, cells lack all surface proteins liknked through GPI anchor)
31
What deficiencies are most commonly associated with infections caused by neisseria meningitis?
Deficiencies in MAC formation (C5 to C9) OR deficiencies in the AP (i.e Factor B and Properidin)
32
What are the effects of a C1Inh deficiency?
Hereditary angioneurotic edema (HAE)
33
Which 3 protein fragment peptides are known as anaphylatoxins?
- C3a - C4a - C5a
34
Which two protein peptide fragments contribute to processes of inflammation?
C3a and C5a
35
What is often done to treat undesired inflammatory responses and tissue damage?
Target neutralization of C3a and C5a or inhibit their receptors (C3aR and C5aR)
36
What are the pathophysiological effects of C3a?
- Contraction of smooth muscle - Increased permeability of blood vessels - Degranulation of basophils
37
What are the pathophysiological effects of C5a?
- Contraction of smooth muscle - Increased permeability of blood vessels - Degranulation of basophils - Chemotaxis, release of O2 radicals and lysosomal enzymes
38
What are the two most important glycosylphosphatidylinositol (GPI) anchor proteins? (essentially they link surface proteins to cellular membranes and help protect RBCs from lysis by complement)
CD55 (DAF) and CD59
39
Ab-based treatments can be used to restore the balance in the complement network in order to achieve therapeutic effects. Activation can be achieved via Fc-induced complement activation -- i.e antiCD20 for ___
B cell lymphomas
40
Ab-based treatments can be used to restore the balance in the complement network in order to achieve therapeutic effects. Inhibition can be achieved by targeting key components of the complement cascade ___, __, __, __, and ___
C1, C3, C5, FI, FD
41
What test measures the CP and its terminal components?
CH50
42
What test measures the AP and its terminal components?
AH50
43
How are the CH50 and AH50 tests used to evaluate the AP and CP pathways?
Both tests involve measuring the ability of the patients serum (containing complement proteins) to lyse sheep RBCs
44
CH50 Test
Defined as the amount of the patient's serum that will lyse 50% of sheep RBCs coated with antibody
45
AH50 Test
Defined as the amount of the patient's serum that will lyse 50% of sheep RBCs that are NOT coated with antibody
46
What does it mean if both AH50 and CH50 test results are abnormal?
It is likely there is a deficiency in one of the terminal pathway components --- defects in C5 and/or C9
47
When should LP be tested for a defect?
- If CH50 is abnormal and AH50 is normal | - Test involves measuring concentration of MBL in the blood by an ELISA
48
What makes up the C3 Convertase in the CP?
C4bC2a
49
What makes up the C5 Convertase in the CP?
C4bC2aC3b
50
What makes up the C3 Convertase in the AP?
C3bBb
51
What makes up the C5 Convertase in the AP?
C3bBbC3b
52
What makes up the C3 Convertase in the LP?
C4bC2a
53
What makes up the C5 Convertase in the LP?
C4bC2aC3b
54
What is the MAC made of?
C5bC6C7C8C9
55
What is required for C1 to bind in the CP?
One IgM or two IgG or C reactive protein
56
What is the role of C3b in the CP and LP?
Opsonization and phagocytosis
57
What is required for initiation of LP?
MBP binds to bacterial surface --> MASPs bind to MBP
58
What is required for initiation of AP?
Nothing - C3 undergoes spontaneous hydrolysis

SFM Immunology (6 decks)

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