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SFM Exam 1 > Complement System > Flashcards

Complement System Flashcards

1
Q

Which proteins are a part of the alternative pathway?

A

C3, factor B, factor D and properdin

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2
Q

Which protein of the alternative pathway has the highest serum concentration?

A

C3

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3
Q

List functions of C3

A

C3b binds to microbial surface and functions as an opsonin
Component of C3 and C5 convertases
C3a stimulates inflammation (anaphylatoxin)

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4
Q

Functions of factor B

A

Bb is a serine protease and the active enzyme of the C3 and C5 convertases

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5
Q

Functions of factor D

A

Plasma serine protease cleaves factor B when it is bound to C3b

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6
Q

Functions of properdin

A

Stabilizes C3 convertase (C3bBb) on microbial surfaces in the alternative pathway

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7
Q

How is the classical pathway initiated?

A

By binding of the C1 to IgG or IgM molecules that bound the Ag

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8
Q

Which proteins are associated with the classical pathway?

A

C1, C1q, C1r, C1s, C4 and C2

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9
Q

Which protein of the classical pathway has the highest plasma concentration?

A

C4

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10
Q

Functions of C1

A

Initiates the classical pathway

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11
Q

Functions of C1q

A

Binds to the Fc portion of the Ab that has bound to an Ag, to apoptotic cells and to cationic surfaces

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12
Q

Functions of C1r

A

Serine protease that cleaves C1s to make it an active protease

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13
Q

C1s function

A

Serine protease that cleaves C4 and C2

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14
Q

C4 functions

A

C4b covalently binds to a microbe and complement is activated
C4b binds C2 for cleavage by C1s
C4a has an unknown function bc no C4aR is found in humans

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15
Q

C2 functions

A

C2a is a serine protease and functions as the active enzyme of C3 and C5 convertases to cleave C3 and C5

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16
Q

How is the lectin pathway initiated?

A

By binding of MBL to bacterial surface and activation of MASP1 and MASP2

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17
Q

Which proteins are associated with the lectin pathway?

A

MBL, MASP1, MASP2 and MASP3

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18
Q

Which lectin pathway protein has the highest plasma concentration?

A

MASP 1 and 2

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19
Q

MBL function

A

Agglutinin, opsonin and complement fixing

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20
Q

MASP1 function

A

Forms complex with MASP2 and collectins or ficolins and activates MASP2/3

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21
Q

MASP2 function

A

Forms complex with lectins especially ficolin-3 and cleaves C4 and C2

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22
Q

MASP3 function

A

Associates with collectins or ficolins and MASP 1, cleaves C4

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23
Q

Which proteins are associated with the lytic pathway?

A

C5-9

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24
Q

Which protein of the lytic pathway has the highest plasma concentration?

A

C7

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25
C5 function
C5b initiates assembly of the MAC and C5a stimulates inflammation
26
C6 function
Component of the MAC | Binds to C5b and accepts C7
27
C7 function
Component of the MAC | Binds to C5b,6 and inserts into lipid membranes
28
C8 function
Component of the MAC | Binds to C5b,6,7 and initiates the polymerization of C9
29
C9 function
Component of the MAC | Polymerizes to form membrane pores
30
What does the classical pathway require?
IgM or 2xIgG and C1
31
Classical pathway C3 convertase
C4bC2a
32
Classical pathway C5 convertase
C4bC2aC3b
33
True or false: The lectin pathway uses C1
False
34
What occurs when MBP from the lectin pathway binds to bacteria?
MASPs are activated
35
Lectin pathway C3 convertase
C4bC2a
36
Lectin pathway C5 convertase
C4bC2aC3b
37
How is the alternative pathway initiated?
C3 undergoes spontaneous hydrolysis
38
Which two factors are needed for the alternative pathway?
Factor B and D
39
Alternative pathway C3 convertase
C3bBb
40
Alternative pathway C5 convertase
C3bBbC3b
41
Functions of C1-INH
Regulates complement activity Inactivates C1r, C1s, MASP 1 and MASP 2 Prevents activation of the CP and LP initiating complexes Also inhibits kallikrein-kirin and coagulation cascades (two other mechanisms of complement activation)
42
Factor I functions
Serine protease that inactivates C3b and C4b Prevents formation of C3 convertase and indirectly the C5 convertase Requires co-factor activity
43
Which regulatory proteins can act as a co-factor for Factor I?
Membrane bound MCP, membrane bound CR1, soluble factor H or soluble C4BP
44
What is the classical C3 convertase de-stabilized by?
DAF, CR1 and C4BP
45
What is the AP C3 convertase destabilized by?
DAF, factor H and CR1
46
Assembly of the MAC complex can be inhibited by what?
CD59 (MACIF), vitronectin and S protein
47
What are the effects of a C1, C2 and C4 deficiency?
Immune complex disease
48
What is the effect of C3 deficiency?
Susceptibility to capsulated bacteria
49
What is the effect of C5-9 deficiency?
Susceptibility to Neisseria
50
What is the effect of Factor D and properdin (factor P) deficiency?
Susceptibility to capsulated bacteria and Neisseria but no immune complex disease
51
What is the effect of a deficiency in Factor I?
Similar effects to C3 deficiency
52
What are the effects of DAF and CD59 deficiency?
Autoimmune-like conditions including paroxysmal nocturnal hemoglobinuria
53
What are the effects of a deficiency in C1-INH?
Hereditary angioneurotic edema (HAE)
54
A CH50 test is defined as the amount of
Patient’s serum that will lyse 50% of sheep RBCs coated with Ab Measures the CP and terminal components
55
The AH50 test is similar to CH50 however
The sheep RBCs are not coated with Ab | Measures the AP and terminal components
56
What would abnormal results in both the CH50 and AH50 indicate?
Defect in C3 or one of the terminal pathway proteins
57
HAE sx include
Edema in various parts of the body including hands, feet, face and airway, excruciating abdominal pain, nausea and vomiting caused by swelling in the intestinal wall
58
What is the cause of swelling in HAE pts?
Bradykinin (C1-INH not present to prevent formation of this molecule)
59
What three lab findings should make you suspect a pt has paroxysmal nocturnal hemoglobinuria (PNH)?
Raised LDH, thrombosis at multiple sites, and anemia and thrombocytopenia
60
What mutation and deficiency do pts with PNH have?
A somatic mutation causes a deficiency in glycosylphosphatidylinositol (GPI) The most important GPI anchor proteins are DAF (CD55) and CD59 which are involved in protecting RBCs from the action of complement
61
What is the most likely cause of intravascular hemolysis in PNH pts?
Increased susceptibility of RBCs to complement
62
Most glomerular diseases are the result of either
Deposition of immune complexes which activate the CP of complement or the result of Abs directly binding to Ags in the kidney
63
What are the two mechanisms that lead to immune mediated vasculitis?
Immune complex deposition and direct Ab interaction
64
Immune complex deposition mediated vasculitis can develop in patients with which diseases?
Pts with Hep B and C infections as well as pts with SLE
65
Deficiencies in complement regulatory protiens can lead to what clincal abnormalities?
PNH and HAE
66
Activation of complement contributes to the pathogenesis of which inflammatory diseases?
Glomerulonephritis and systemic vasculitis

SFM Exam 1 (8 decks)

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