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x- immunology micr 3230 > Complement System > Flashcards

Complement System Flashcards

1
Q

What form do compliment serum proteins circulate in?

A

inactive

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2
Q

What are 4 possible outcomes of complement system activation?

A

target cell membrane lysis
chemotaxis
opsonization - promote phagocytosis
inflammation

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3
Q

What are the 7 steps?

A
  1. Initiators bind
  2. Conformational changes
  3. Opsonization
  4. Inflammation
  5. MAC
  6. effectors act through complement receptors
  7. limit effects by promoting degradation/ preventing host binding
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4
Q

What is an example of an opsonin?

A

C1q

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5
Q

What are the 3 activation pathways?

A

classical/ lectin/ alternative

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6
Q

What complement protein do all 3 pathways generate?

A

C3b

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7
Q

What pathway is associated with antigen-antibody immune complexes?

A

classical pathway

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8
Q

What pathway is associated with PAMP recognition by lectins? recognize carbs

A

lectin pathway

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9
Q

What pathway is associated with spontaneous hydrolysis?

A

alternative pathway

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10
Q

What begins the process of complement deposition?

A

binding of C1q

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11
Q

What is the C1 complex made up of?

A

C1q opsonin/ C1r2s2 enzyme/protease ring
= C1qr2s2

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12
Q

What is the protease C1r2s2 composed of?

A

2 C1r / 2 C1s

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13
Q

What happens after opsonin C1q binds the antigen-antibody complex?

A

conformational change in 1 C1r molecule= activates it

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14
Q

What happens after first C1r molecule activated?

A

it activates the second C1r and the 2 C1s molecules

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15
Q

What does C1s do?

A

cleaves C4/ C2

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16
Q

What is cleaved by C1s first, C4 or C2?

A

C4

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17
Q

What happens to the components of C4 cleaved by C1s?

A

C4b- binds C2 and exposes it to C1s
C4a - away

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18
Q

What happens when C2 is cleaved by C1s?

A

C3 convertase formed = C4b2a

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19
Q

What is C3 convertase?

A

C4b2a

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20
Q

What happens to C2 components once cleaved by C1s?

A

C2a- into C3 complex
C2b- away

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21
Q

What hydrolyzes many C3 molecules?

A

C3 convertase

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22
Q

What combines to form C5 convertase?

A

C3 convertases combine with C3
= C4b2a + C3b = C4b2a3b

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23
Q

What is C5 convertase?

A

C4b2a3b

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24
Q

What part of C5 convertase binds C5?

A

C3b

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25
Q

What happens once C5 binds to C5 convertase?

A

C4b2a cleaves C5

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26
Q

What is C1 binding followed by?

A

cleavage of C4 then C2

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27
Q

What is another term for lectins?

A

Mannose-binding lectin = MBL

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28
Q

What do lectins bind to?

A

microbial surfaces

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29
Q

What is the function of lectins?

A

bind to microbial surface/ serve as docking sites for MASPs
= MBL associated serine proteases

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30
Q

What do MASPs do? (lectin)

A

cleave C4/ C2 to form C3 convertase

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31
Q

What are the 3 ways the alternative pathway is initiated?

A
  1. alternative tickover pathway
  2. alternative properdin-activated
  3. alternative protease-activated
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32
Q

What pathway describes how small amounts of C3 are always being cleaved/ activated C3b binds to membrane/ Factor B binds and is cleaved by Factor D?

A

alternative tickover

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33
Q

What does factor D do?

A

cleaves factor B into Bb

34
Q

What does C3b bound to factor B form once factor B cleaved by factor D?

A

C3bBb

35
Q

What is the C3 convertase in alternative pathway?

A

C3bBb

36
Q

What stabilizes the C3 convertase?

A

properdin

37
Q

What does properdin do after stabillizes C3 convertase?

A

cleaves more C3 proteins

38
Q

What is the C5 convertase in alternative pathway?

A

C3bBbC3b

39
Q

How does alternative C5 convertase form?

A

newly active C3 binds to C3bBb

40
Q

What pathway is related to the clotting cascade?

A

alternative protease-activated

41
Q

What has been shown to stimulate cleavage of compliment proteins?

A

initiation of clotting cascades

42
Q

What serves as an opsonin- binds covalently ti microbial cells/ serves as ligands for phagocytic cells with receptors for it?

A

C3b

43
Q

What is C3b related to in all 3 pathways?

A

opsonization/ tagging cells for phagocytosis

44
Q

In the classical/lectin pathways what forms C5 convertase?

A

C3b + C4b + C2a

45
Q

What forms C3 convertase in alternative pathway?

A

C3b + Bb

46
Q

What forms C5 convertase in alternative pathway?

A

C3b + Bb + C3b

47
Q

What organ synthesizes all the C proteins?

A

liver

48
Q

What are serum proteins?

A

inactive form (C)

49
Q

How is the compliment system activated?

A

when stimulated by trigger/ pathogen, proteases cleave specific proteins to release cytokines/ initiate cascade

50
Q

What are the 2 end results of complement activation?

A

stimulation of phagocytosis
activation of MAC

51
Q

Where do the 3 complement pathways converge?

A

formation of C5 convertase

52
Q

What is the role of C5 convertase?

A

cleave C5 into C5a/ C5b

53
Q

What initiates the formation of MAC?

A

C5

54
Q

What is the MAC result of?

A

deposition of C5b/ C6/C7/C8/C9 = terminal components

55
Q

How do the terminal components result in cell death MAC?

A

pore structure disrupts osmotic integrity

56
Q

What are the 3 main classes of complement activity?

A

innate defences against infection
interfere between innate/ adaptive immunity
compliment contraction phase immune response

57
Q

What are some innate defences against infection by complement activity?

A

lysis of microbial cell membranes- MAC
opsonization/ inflammation/ chemotaxis

58
Q

What connects compliment-tagged pathogens to effector cells?

A

complement receptors

59
Q

What cells is CR1 on?

A

leukocytes/ erythrocytes

60
Q

What does CR1 do on RBCs?

A

bring immune complexes to liver for clearance by phagocytosis

61
Q

What on phagocytes helps bind to compliment coated bacteria to enhance ingestion/ destruction?

A

CR1

62
Q

What does CR1 do on B cells?

A

enhance ingestion for processing/ presentation to helper T cells

63
Q

What compliment receptor is on B cells?

A

CR2

64
Q

What compliment receptor is on RBC/ leukocytes?

A

CR1

65
Q

What connects compliment-tagged pathogens to effector cells?

A

Compliment receptors

66
Q

What does CR2 do on B cells?

A

binds to C3b
provides secondary signals through BCR

67
Q

What complement receptor is on granulocytes?

A

C3aR/ C5aR

68
Q

What are known as “bridges” between complement components/ cells they bind?

A

CRs

69
Q

What do C3aR/ C5aR do on granulocytes?

A

stimulate release of proinflammatory cytokines from basophils/ eosinophils/ neutrophils

70
Q

What regulates complement activity?

A

protein stability

71
Q

What provides host cell protection against prolonged periods of complement activation?

A

relative instability/ short half-life of C3 convertase unless stabilized by properdin

72
Q

What is the C1 inhibitor?

A

C1INH

73
Q

What does C1INH do?

A

promotes dissociation of C1 components = inhibitor

74
Q

What is the result of C1INH binding to active site of serine proteases?

A

causes C1r2s2 to dissociate from C1q
-no further cleavage possible

75
Q

What inhibits the initiation of classical/ lectin pathways?

A

C1NH = C1 inhibitor

76
Q

What is C3 convertase?

A

C4b2a/ C3bBb

77
Q

What degrades C3b/ C4b?

A

factor I

78
Q

What inhibits MAC complex?

A

Protectin

79
Q

What prevents insertion into host cell PM?
- MAC inhibition prevent C9?
inhibition of lysis?

A

S protein = umbrella

80
Q

What can carboxypeptidases do?

A

inactivate C3a/ C5a anaphylatoxins

81
Q

Deficiency of C1q/C1r/C4/C2 often present with immune disorders due to inadequate what?

A

clearance

82
Q

Why would someone with MBL deficiency echibit greater frequency of infections?

A

by encapsulated pathogens due to inefficient opsonization/ phagocytosis

x- immunology micr 3230 (11 decks)

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