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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
What happens once C5 binds to C5 convertase?
C4b2a cleaves C5
26
What is C1 binding followed by?
cleavage of C4 then C2
27
What is another term for lectins?
Mannose-binding lectin = MBL
28
What do lectins bind to?
microbial surfaces
29
What is the function of lectins?
bind to microbial surface/ serve as docking sites for MASPs = MBL associated serine proteases
30
What do MASPs do? (lectin)
cleave C4/ C2 to form C3 convertase
31
What are the 3 ways the alternative pathway is initiated?
1. alternative tickover pathway 2. alternative properdin-activated 3. alternative protease-activated
32
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?
alternative tickover
33
What does factor D do?
cleaves factor B into Bb
34
What does C3b bound to factor B form once factor B cleaved by factor D?
C3bBb
35
What is the C3 convertase in alternative pathway?
C3bBb
36
What stabilizes the C3 convertase?
properdin
37
What does properdin do after stabillizes C3 convertase?
cleaves more C3 proteins
38
What is the C5 convertase in alternative pathway?
C3bBbC3b
39
How does alternative C5 convertase form?
newly active C3 binds to C3bBb
40
What pathway is related to the clotting cascade?
alternative protease-activated
41
What has been shown to stimulate cleavage of compliment proteins?
initiation of clotting cascades
42
What serves as an opsonin- binds covalently ti microbial cells/ serves as ligands for phagocytic cells with receptors for it?
C3b
43
What is C3b related to in all 3 pathways?
opsonization/ tagging cells for phagocytosis
44
In the classical/lectin pathways what forms C5 convertase?
C3b + C4b + C2a
45
What forms C3 convertase in alternative pathway?
C3b + Bb
46
What forms C5 convertase in alternative pathway?
C3b + Bb + C3b
47
What organ synthesizes all the C proteins?
liver
48
What are serum proteins?
inactive form (C)
49
How is the compliment system activated?
when stimulated by trigger/ pathogen, proteases cleave specific proteins to release cytokines/ initiate cascade
50
What are the 2 end results of complement activation?
stimulation of phagocytosis activation of MAC
51
Where do the 3 complement pathways converge?
formation of C5 convertase
52
What is the role of C5 convertase?
cleave C5 into C5a/ C5b
53
What initiates the formation of MAC?
C5
54
What is the MAC result of?
deposition of C5b/ C6/C7/C8/C9 = terminal components
55
How do the terminal components result in cell death MAC?
pore structure disrupts osmotic integrity
56
What are the 3 main classes of complement activity?
innate defences against infection interfere between innate/ adaptive immunity compliment contraction phase immune response
57
What are some innate defences against infection by complement activity?
lysis of microbial cell membranes- MAC opsonization/ inflammation/ chemotaxis
58
What connects compliment-tagged pathogens to effector cells?
complement receptors
59
What cells is CR1 on?
leukocytes/ erythrocytes
60
What does CR1 do on RBCs?
bring immune complexes to liver for clearance by phagocytosis
61
What on phagocytes helps bind to compliment coated bacteria to enhance ingestion/ destruction?
CR1
62
What does CR1 do on B cells?
enhance ingestion for processing/ presentation to helper T cells
63
What compliment receptor is on B cells?
CR2
64
What compliment receptor is on RBC/ leukocytes?
CR1
65
What connects compliment-tagged pathogens to effector cells?
Compliment receptors
66
What does CR2 do on B cells?
binds to C3b provides secondary signals through BCR
67
What complement receptor is on granulocytes?
C3aR/ C5aR
68
What are known as "bridges" between complement components/ cells they bind?
CRs
69
What do C3aR/ C5aR do on granulocytes?
stimulate release of proinflammatory cytokines from basophils/ eosinophils/ neutrophils
70
What regulates complement activity?
protein stability
71
What provides host cell protection against prolonged periods of complement activation?
relative instability/ short half-life of C3 convertase unless stabilized by properdin
72
What is the C1 inhibitor?
C1INH
73
What does C1INH do?
promotes dissociation of C1 components = inhibitor
74
What is the result of C1INH binding to active site of serine proteases?
causes C1r2s2 to dissociate from C1q -no further cleavage possible
75
What inhibits the initiation of classical/ lectin pathways?
C1NH = C1 inhibitor
76
What is C3 convertase?
C4b2a/ C3bBb
77
What degrades C3b/ C4b?
factor I
78
What inhibits MAC complex?
Protectin
79
What prevents insertion into host cell PM? - MAC inhibition prevent C9? inhibition of lysis?
S protein = umbrella
80
What can carboxypeptidases do?
inactivate C3a/ C5a anaphylatoxins
81
Deficiency of C1q/C1r/C4/C2 often present with immune disorders due to inadequate what?
clearance
82
Why would someone with MBL deficiency echibit greater frequency of infections?
by encapsulated pathogens due to inefficient opsonization/ phagocytosis

x- Immunology MICR 3230 (11 decks)

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