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Infection and Immunity > 8 Complement > Flashcards

8 Complement Flashcards

1
Q

Innate Immune response – recognition

A

Bacterial cell surface induces cleavage and complement activation
One complement fragment covalently binds to bacterium, other attracts an effector cell
Complement receptor on effector cell binds to complement fragment on bacterium
Effector cell engulfs bacterium, kills it and breaks down

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2
Q

Stages of complement action

A

Pattern recognition trigger
Protease cascade amplification/C3 convertase
Inflammation, phagocytosis, membrane attack

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3
Q

can complement kill

A

complement can directly kill through the membrane attack complex

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4
Q

Complement pathways

A

antibody dependent

antibody independent

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5
Q

Antibody dependent complement pathways

A

classical pathway

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6
Q

Antibody independent complement pathways

A

lectin pathway and alternative pathway

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7
Q

when is the lectin pathway activated

A

activated as soon as antigen in body – direct recognition of pathogen

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8
Q

when is the alternative pathway activated

A

once complement is activated even more complement is activated

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9
Q

when is the classical pathway activated

A

pathogen has to be recognised, producing antibodies

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10
Q

what do the three pathways lead to

A

Three pathways all lead to activation of C3 and generation of C5 convertase
Activation of C5

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11
Q

what happens in the classical pathway

A

antibodies bind to specific antigen on pathogen surface

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12
Q

what happens in the lectin pathway

A

mannose-binding lectin binds to pathogen surface

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13
Q

what happens in the alternative pathway

A

pathogen surface creates local environment conductive to complement activation

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14
Q

what does the C3 molecule lead to

A

All lead to C3 molecule – which in the end leads to the membrane attack complex

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15
Q

Physiological consequences of complement activation

A 
Bacteria = lysis
Phagocyte = chemotaxis
Bacteria = opsonization
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16
Q

what is lysis

A

forming holes in membrane – membrane attack complex

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17
Q

what is opsonization

A

tagging of pathogen to see something foreign in the body

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18
Q

Components of lectin pathway

A

Mannose groups
Mannose Binding Lectin
C4
C2

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19
Q

what are the enzymes in the lectin pathway

A

Enzymes: MASP2 and MASP1

serine proteases

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20
Q

what do the enzymes in the lectin pathway do

A

switch on the process when activated

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21
Q

what activates the enzymes in the lectin pathway

A

When mannose bind lectin binds to the mannose groups on surface = activation of MASP1 and MASP

22
Q

what does MASP1 do

A

activates MASP2

23
Q

what does MASP2 do

A

cleaves C4 into C4a and C4b

24
Q

how is C3 convertase made in the lectin pathway

A

C2 cleaved into C2a and C2b

C2a joins onto pathogen surface with C4a = C3 convertase

25
Q

how is a C5 convertase generated in lectin pathway

A

one molecule of C4b2a can cleave C3 to C3b, C3b bind to microbial surface (deposition on pathogen surface)
C4b2a3b = C5
C5 convertase leads to membrane attack complex

26
Q

Components of classical pathway

A

C1, C2, C3, C4

27
Q

what is C1 complex

A

made of C1q and C1r and C1s (serine proteases C1r and C1s – to activate need to be bound to two IgG or IgM = conformational change)

28
Q

how is the classical pathway initiated

A

Pentameric IgM molecule binds to antigens on bacterial surface and adopts ‘staple’ form
C1 binds to single IgM molecule
IgG molecules bind to antigens on bacterial surface
C1q binds to two or more IgG molecules

29
Q

how is a C3 convertase generated in classical pathway

A

Activated C1s cleaves C4 to C4a and C4b. some C4b binds covalently to microbial surface
Activated C1s also cleaves C2 to C2a and C2b

30
Q

how is a C5 convertase generated in the classical binding pathway

A

C2a binds to surface C4b forming classical C3 convertase, C4b2a

31
Q

what does the C4b2a do in the classical pathway

A

binds C3 and cleaves C3a into C3b

32
Q

what does C3a do

A

causes inflammation, mast cells to degranulate

33
Q

what does the C3b made in the classical pathway do

A

binds covalently to microbial surface

34
Q

Components of the alternative pathway

A

C3b
factor b
factor d
properdin

35
Q

what does factor b do in the alternative pathway

A

binds to C3b makes alternative pathway C3b

36
Q

what does factor d do in the alternative pathway

A

plasma serine protease, cleave B when it is bound to C3b to Ba and Bb

37
Q

how is C3 generated in alternative pathway

A

C3bBb = C3 convertase of alternative pathway
C3b deposited by classical or lectin pathway C3 converase
C3b binds to factor B = C3bB
Bound factor B is cleaved by plasma protease factor D into Ba and Bb
C3bBb complex is C3 convertase, cleaving many C3 molecules to C3a and C3b

38
Q

what is C3a needed for

A

mast cell activation

39
Q

what is C3b needed for

A

C3b to get more C3a

40
Q

C5 function in the membrane attack complex

A

on activation the soluble C4b initiates assembly of MAC in solution

41
Q

C6 function in the membrane attack complex

A

binds to and stabilises C5b, forming C7 binding site

42
Q

C7 function in the membrane attack complex

A

binds to C5b, 6 and exposes a hydrophobic region that permits attachment to cell membrane

43
Q

C8 function in the membrane attack complex

A

binds to C5b, 6, 7 and exposes a hydrophobic region that inserts into cell

44
Q

C9 function in the membrane attack complex

A

polymerization on C5b, 6, 7, 8 complex, form membrane-spanning channel that disrupts cell’s integrity and can cause cell death

45
Q

what does opsonization and phagocytosis do

A

C3b and C4b of complement binds tagging for phagocytosis

46
Q

Cellular recruitment and activation

A

Increased vascular permeability
Vasodilation
C5a and C3a activates mast cell= cellular recruitment and inflammation
Chemo-attractive properties = chemotaxis

47
Q

what leads to inflammation

A

C3a and C5a

48
Q

what do mast cells lead to

A

C3a, C5a, PAMPs damage

49
Q

what are the complement functions

A

host benefit

host detriment

50
Q

complement - Host benefit

A
  • opsonization to enhance phagocytosis
  • phagocyte attraction and activation
  • lysis of bacteria and infected cells
  • regulation of antibody responses
  • clearance of immune complexes
  • clearance of apoptotic cells
51
Q

complement - Host detriment

A
  • inflammation (through C3a/C5a and mast cells)

- anaphylaxis

Infection and Immunity (29 decks)

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