Immunology > Complement System > Flashcards

Complement System Flashcards

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1
Q

What is the compliment system?

A

Major part of innate humerol immunity
Around 30 plasma proteins - mostly liver derived - but also produced by myeloid cells

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2
Q

What is the compliment system activated by?

A

Proteolytic cascades- series of enzymatic cascades each step activating the next

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3
Q

End result of the compliment system

A

Inflammation
Opsonisation
Microbial lysis

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4
Q

Key components of the complement system

A

Activation proteins
Opsonins
Anaphylatoxins
Mac components
Regulators

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5
Q

Examples of activated proteins

A

C1
C4
C2
C3
C5

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6
Q

Function of activation proteins

A

Form convertases

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7
Q

Opsonins examples

A

C3b
IC3b
C4b

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8
Q

function of Opsonins

A

Tag microbes for phagocytosis

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9
Q

Examples of anaphylatoxins

A

C3a
C4a
C5a

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10
Q

Function of anaphylatoxins

A

Inflammation
Recruit leukocytes

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11
Q

MAC components examples

A

C5b
C6
C7
C8
C9

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12
Q

Function of mac components

A

Cell lysis

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13
Q

Regulators examples

A

C1-INH
Factor H
Factor I
DAF (CD55)
MCP (CD46) CD59

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14
Q

Function of regulators

A

Prevent host damage

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15
Q

What is b in complement proteins usually?

A

Large fragment

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16
Q

What is the exception of the an and b nomenclature?

A

C2 (reversed)

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17
Q

What is a usually in complement proteins?

A

Small fragments

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18
Q

What are the different pathways in complement system?

A

Classical
Lectin
Alternative

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19
Q

What triggers the classical pathway?

A

Antibody-antigen complexes (1 IgM or multiple IgGs)
CRP or direct C1q binding to microbes

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20
Q

What triggers the lectin pathway?

A

MBL or ficolins binding to sugars eg mannose on microbes

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21
Q

What triggers the alternative pathway?

A

Spontaneous C3 hydrolysis
Microbial surfaces stabilise C3b

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22
Q

Classical pathway sequence

A

C1q binds
This activates C1r and C1s
C1s cleaves C4
C4 turns to C4a and C4b
C4b binds C2 -
C1s cleaves
Makes C4b2a

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23
Q

What is C4b2a also called?

A

C3 convertase

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24
Q

Does classical pathway require antibody?

A

Typically yes

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25
What does lectin pathway activate?
MASP-1/2 (C1r/C1s-like)
26
Lectin pathway sequence
MBL binds sugar MASP-1/2 cleaves C4 and C2 This produces C4b2a - same C3 convertase as classical!
27
Does lectin pathway require antibodies?
No
28
What does alternative pathway require?
Factor B and D
29
Alternative pathway sequence
C3b binds factor B Factor D cleaves B Turns into Bb This forms C3bBb (C3 convertase) Amplification loop generates more C3b
30
Does alternative pathway require antibodies?
No
31
How much of total compliment activation does alternative pathway contribute?
80-90%
32
What does cleave mean here?
Cut protein into 2 fragments - small and big aka an and b. Inactive Zymogens turn active when pathway activated and that’s when protease enzymes cut them
33
Classical and lectin pathway C3 convertase
C4b2a = C4b + C2a
34
Alternative pathway C3 convertase
C3bBb = C3b + Bb
35
Convertases cleave…
C3 into C3a + C3b
36
C3b binds to..
Microbes causing opsonisation
37
What happens when there’s more C3b deposition
Formation of C5 convertase
38
Classical/lectin pathway C5 convertase
C4b2a3b
39
Alternative pathway C5 convertase
C3bBb3b
40
Function of C5 convertase
CleavesC5 Forms C5a + C5b
41
What does C5b do?
Initiates MAC formation
42
What does C5a do?
It is a potent anaphylatoxin Chemoattractant
43
Downstream function of C3b/iC3b
Opsonisation
44
Downstream function of C5a, C3a
inflammation
45
Downstream functions of C5b-9
MAC Cell lysis
46
What are the major functions of complement system?
Opsonisation Clearance of apoptotic Cells and immmune complexes Cell lysis (MAC) Inflammation
47
How does opsonisation occur from complement system
C3b binds microbe This is recognised by CR1/CR3 Factor I converts C3b into iC3b
48
How does cell lysis occur from complement system
C5b recruits C6-C9 C9 polymerises This creates a pore which causes osmotic lysis
49
What is cell lysis (MAC) effective against?
Neisseria
50
How does inflammation occur from complement system
C3a, C4a and C5a are anaphylatoxins C5a is strongest = nutrophil chemotacis C3a used in mast cell degranulation
51
How does clearance of apoptotic cells and immune complexes occur from complement system?
C1q and C3b facilitate debris removal Failure of this is autoimmunity
52
Why do we need to regulate complement system?
Prevent damage to host Convertases amplify rapidly To prevent bystander activation
53
Examples of major regulators
C1 inhibitor C1-INH DAF (CD55) Factor H MCP (CD46) Factor I CR1 CD59
54
What does C1 inhibitor do?
Stops C1r/C1s and MASPs This prevents classical/lectin overactivation
55
What does DAF do?
Displaces C2a or Bb This breaks C3 convertases
56
What Does factor H do?
Binds C3b on host cells This prevents alternative pathway
57
What does MCP do?
Co-factor for factor I to inactivate C3b
58
What does factor I do?
Cleaves C3b and C4b This forms inactive versions of them
59
What does CR1 do?
Promotes breakdown of both C3 and C5 convertases
60
What does CD59 do?
Blocks C9 polymerisation Prevents MAC on host cells
61
Early component deficiencies ie C1q, C2,C4
Increased autoimmune disease Poor immune complex clearance Increases bacterial and yeast infections
62
C3 deficiencies
Severe recurrent pyogenic infections Eg s. Pneumoniae Most serious deficiencies since C3 is central.
63
C1-INH deficiency leads to..
Hereditary angioedema
64
Factor I deficiency leads to..
Overactivation causing Recurrent infections
65
Factor H deficiency leads to..
Atypical HUS Age. Related macular degeneration
66
Terminal pathway deficiencies (C5-C9)
Surprisingly mild High susceptibility to neisseria
Immunology
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