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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
Q

C5 function

A

C5b initiates assembly of the MAC and C5a stimulates inflammation

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26
Q

C6 function

A

Component of the MAC

Binds to C5b and accepts C7

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27
Q

C7 function

A

Component of the MAC

Binds to C5b,6 and inserts into lipid membranes

28
Q

C8 function

A

Component of the MAC

Binds to C5b,6,7 and initiates the polymerization of C9

29
Q

C9 function

A

Component of the MAC

Polymerizes to form membrane pores

30
Q

What does the classical pathway require?

A

IgM or 2xIgG and C1

31
Q

Classical pathway C3 convertase

A

C4bC2a

32
Q

Classical pathway C5 convertase

A

C4bC2aC3b

33
Q

True or false: The lectin pathway uses C1

A

False

34
Q

What occurs when MBP from the lectin pathway binds to bacteria?

A

MASPs are activated

35
Q

Lectin pathway C3 convertase

A

C4bC2a

36
Q

Lectin pathway C5 convertase

A

C4bC2aC3b

37
Q

How is the alternative pathway initiated?

A

C3 undergoes spontaneous hydrolysis

38
Q

Which two factors are needed for the alternative pathway?

A

Factor B and D

39
Q

Alternative pathway C3 convertase

A

C3bBb

40
Q

Alternative pathway C5 convertase

A

C3bBbC3b

41
Q

Functions of C1-INH

A

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
Q

Factor I functions

A

Serine protease that inactivates C3b and C4b
Prevents formation of C3 convertase and indirectly the C5 convertase
Requires co-factor activity

43
Q

Which regulatory proteins can act as a co-factor for Factor I?

A

Membrane bound MCP, membrane bound CR1, soluble factor H or soluble C4BP

44
Q

What is the classical C3 convertase de-stabilized by?

A

DAF, CR1 and C4BP

45
Q

What is the AP C3 convertase destabilized by?

A

DAF, factor H and CR1

46
Q

Assembly of the MAC complex can be inhibited by what?

A

CD59 (MACIF), vitronectin and S protein

47
Q

What are the effects of a C1, C2 and C4 deficiency?

A

Immune complex disease

48
Q

What is the effect of C3 deficiency?

A

Susceptibility to capsulated bacteria

49
Q

What is the effect of C5-9 deficiency?

A

Susceptibility to Neisseria

50
Q

What is the effect of Factor D and properdin (factor P) deficiency?

A

Susceptibility to capsulated bacteria and Neisseria but no immune complex disease

51
Q

What is the effect of a deficiency in Factor I?

A

Similar effects to C3 deficiency

52
Q

What are the effects of DAF and CD59 deficiency?

A

Autoimmune-like conditions including paroxysmal nocturnal hemoglobinuria

53
Q

What are the effects of a deficiency in C1-INH?

A

Hereditary angioneurotic edema (HAE)

54
Q

A CH50 test is defined as the amount of

A

Patient’s serum that will lyse 50% of sheep RBCs coated with Ab
Measures the CP and terminal components

55
Q

The AH50 test is similar to CH50 however

A

The sheep RBCs are not coated with Ab

Measures the AP and terminal components

56
Q

What would abnormal results in both the CH50 and AH50 indicate?

A

Defect in C3 or one of the terminal pathway proteins

57
Q

HAE sx include

A

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
Q

What is the cause of swelling in HAE pts?

A

Bradykinin (C1-INH not present to prevent formation of this molecule)

59
Q

What three lab findings should make you suspect a pt has paroxysmal nocturnal hemoglobinuria (PNH)?

A

Raised LDH, thrombosis at multiple sites, and anemia and thrombocytopenia

60
Q

What mutation and deficiency do pts with PNH have?

A

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
Q

What is the most likely cause of intravascular hemolysis in PNH pts?

A

Increased susceptibility of RBCs to complement

62
Q

Most glomerular diseases are the result of either

A

Deposition of immune complexes which activate the CP of complement or the result of Abs directly binding to Ags in the kidney

63
Q

What are the two mechanisms that lead to immune mediated vasculitis?

A

Immune complex deposition and direct Ab interaction

64
Q

Immune complex deposition mediated vasculitis can develop in patients with which diseases?

A

Pts with Hep B and C infections as well as pts with SLE

65
Q

Deficiencies in complement regulatory protiens can lead to what clincal abnormalities?

A

PNH and HAE

66
Q

Activation of complement contributes to the pathogenesis of which inflammatory diseases?

A

Glomerulonephritis and systemic vasculitis

SFM Exam 1 (8 decks)

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