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Biochemistry > Complement System > Flashcards

Complement System Flashcards

1
Q

The classical pathway forms _______ complexes.

A

antigen:antibody

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2
Q

Membrane cofactor protein (MCP) promotes:

A

C3b and C4b inactivation

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3
Q

What kind of bond gets exposed by a protease during the cleavage of C3 into C3a and C3b?

A

thioester bond (nucleophile)

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4
Q

A C5 convertase is composed of ___.

A

C3b+Bb+C3b

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5
Q

C3 convertase directly leads to the activation of which proteins of the complement system?

A

C3a, C5a, C3b

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6
Q

What is the formula for the C1 complex?

A

C1q:C1r(2):C1s(2)

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7
Q

The cleavage of C4 and C2 by C1s forms the _____.

A

C4b2a complex

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8
Q

What does C4b do?

A

binds to pathogen and starts the opsonization process; binds C2 for cleavage by C1s

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9
Q

C1s cleaves ___ and then cleaves ___.

A

C4; C2

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10
Q

Why does complement activation work to destroy bacterial cells but not allow the destruction of our own cells?

A

because the factors that regulate the complement pathway are bound to the membrane of normal cells to block the complement cascade from happening

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11
Q

Kallikrein can lead to the activation of _____, which causes vasodilation, nonvascular smooth muscle contraction, edema, and activation of the complement cascade.

A

bradykinin

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12
Q

The release of serum into the tissues, marked by swelling, is called ____.

A

wheal

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13
Q

DAF ____ the association of factor B with C3b, thereby preventing the formation of additional C3 convertase.

A

blocks

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14
Q

Which active component of the terminal complement components allows insertion into the cell membrane to begin formation of the MAC?

A

C8

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15
Q

At which level is the alternative pathway continuously activated?

A

low level

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16
Q

What is C1r responsible for?

A

it cleaves C1s to active protease

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17
Q

The C4b/C2a complex is responsible for cleaving ___.

A

C3

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18
Q

Does the alternative pathway rely on pathogen-binding antibodies?

A

NO

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19
Q

What is a prothrombotic state, in regards to complement-mediated cell injury?

A

exposure of subendothelial collagens and release of von Willebrand factor and fibrinogen formation

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20
Q

Ficolins have a very similar structure to MBL. However, they bind _____.

A

carbohydrates

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21
Q

The globular heads of ___ bind to the surface of the cell to bind with the antibodies/immunoglobulins.

A

C1q

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22
Q

What does C4a do?

A

weak inflammatory activity

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23
Q

Which protein causes opsonization?

A

C3b

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24
Q

MBL and ficolin function the SAME, but contain different ___.

A

domains

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25
Q

What happens when C3b binds to CR1 on a macrophage?

A

nothing; bacteria cannot be phagocytosed

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26
Q

What is C1q responsible for?

A

it binds directly to pathogen surfaces or indirectly to antibody bound to the pathogen, allowing the auto-activation of C1r

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27
Q

C4 gets cleaved into ___ and ___.

A

C4b; C4a

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28
Q

How is the therapeutic inhibition of C5 complement by Eculizumab clinically significant?

A

Eculizumab blocks C5 convertase in converting C5 into C5a; C5a initiates the MAC complex that forms pores and lyses cells; by blocking the formation of C5a, the MAC complex is not formed (thereby keeping host cells intact)

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29
Q

In the alternative pathway, C3 is cleaved into C3b. What is the role of C3b?

A

it binds to pathogen surface; binds factor B for cleavage by factor D

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30
Q

The Classic Complement Pathway is triggered by the activation of the ___ complex.

A

C1

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31
Q

_____ promotes removal of particles via complement receptors on host cells, and leads to assembly of the membrane attack complex.

A

Opsonization

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32
Q

Inflammation is marked by:

A

capillary dilation, leukocytic infiltration, redness, heat, and pain

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33
Q

We have a genetic predisposition to which kind of immunity?

A

innate immunity

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34
Q

DAF inhibits the assembly of classical and alternative pathway _____.

A

C3 convertases

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35
Q

When lectins bind to carbohydrates, which pathway is engaged?

A

lectin pathway (LP)

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36
Q

Upon binding of MBL to the bacterial surface, ____ and ____ become activated and then activate the complement system by cleaving C4 and C2.

A

MASP-1; MASP-2

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37
Q

The classical pathway utilizes the _____ complex, whereas the lectin pathway utilizes the _____ complex.

A

C1q, C1r, C1s; MASP-1/MASP-2 (MBL)

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38
Q

The release of ____ promotes cell activation (mast cell degranulation) or migration to the inflammatory site (chemotaxis).

A

anaphylatoxins

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39
Q

Which active component of the terminal complement components initiates the assembly of the membrane-attack complex?

A

C5b

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40
Q

Which proteins of the complement system mediate inflammation and phagocyte recruitment?

A

C3a, C5a

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41
Q

__ is the active enzyme of C3 convertase C3bBb and C5 convertase C3b2Bb.

A

Bb

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42
Q

DAF accelerates the _____ of Bb from C3b in formed C3 convertase (C3bBb), which stops the production of additional C3b.

A

dissociation

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43
Q

___ gets bound to the surface of the pathogen, coating its surface, after being attacked by a nucleophilic group.

A

C3b

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44
Q

Which pathway does the natural, spontaneous complement mechanism engage?

A

alternative pathway (AP)

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45
Q

____ serves as a mechanism initiating the elimination of noxious agents and damaged tissues.

A

Inflammation

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46
Q

C4b2a facilities the amplification of C3b for opsonization. How?

A

one molecule of C4b2a can cleave thousands of C3 molecules into C3b, which stick to the bacterial surface and coat it

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47
Q

Which protein initiates the effector pathway?

A

C5b

48
Q

____ is a plasma protein that stabilizes the C3 convertase C3bBb on bacterial cells.

A

Properdin

49
Q

What is the ultimate goal of complement system pathways?

A

to lead to the membrane attack complex (MAC)

50
Q

The alternative pathway ____ contain the antibody-binding first step.

A

DOES NOT

51
Q

On which targets does the complement system become activated on?

A

apoptotic cells, tissue debris, pathogens

52
Q

In _____ immunity, natural antibodies are replaced by specific antibodies.

A

adaptive

53
Q

___ and ___ dissociate C3 convertases on human cells.

A

DAF; MCP

54
Q

What deposits C3b onto the bacterial cell surface in the alternative complement pathway?

A

C3 convertase of the classical or lectin pathways

55
Q

The cleavage of C5 into C5b and C5a generates ___ and ___, respectively.

A

membrane attack complex (MAC); a potent pro-inflammatory mediator

56
Q

Which immune system (innate/adaptive) involves lymphocytes (T and B cells) that can recognize and deactivate specific antigens?

A

adaptive immune system

57
Q

Which factor cleaves bound factor B when it is bound to C3b?

A

Factor D

58
Q

Elements from which immune system (innate/adaptive) include mucous secretions, complement proteins, and neutrophils, macrophages, and dendritic cells?

A

innate immune system

59
Q

What are the terminal complement components?

A

C5b, C6, C7, C8, C9

60
Q

When opsonization and destruction happens to normal cells and not bacterial cells it can cause an ______.

A

autoimmune disease

61
Q

Bound factor B is cleaved by factor D and then the C3bBb complex cleaves many ___.

A

C3 molecules

62
Q

C3a and C5a are ______.

A

anaphylatoxins

63
Q

C3 and MCP are made in the ____.

A

liver

64
Q

Which pathway does the binding of a targeted, naturally occurring antibody engage?

A

classical pathway (CP)

65
Q

Complement triggers:

A

1) phagocytosis
2) inflammation
3) membrane attack

66
Q

What are the two complements?

A

membrane perturbation and inflammation

67
Q

C3a mediates intermediate ______.

A

inflammation

68
Q

The central component of the complement system is _____.

A

complement fixation

69
Q

Each of the cleavage steps in the production of C3b leads to _____, and staggering proportions of the protein.

A

amplification

70
Q

How is the complement system activated mechanistically?

A

1) natural - spontaneous turnover of C3 engages the alternative pathway
2) antibody binding - engages the classical pathway
3) lectin to carbohydrate binding - engages the lectin pathway

71
Q

Do MBL and ficolins have the same basic function? Do they utilize the same enzyme?

A

YES; NO

72
Q

Complement is activated by a series of ____ that are ____ and create this cascade.

A

proteins; enzymes

73
Q

C1 is a complex of _____.

A

C1q, C1r & C1s

74
Q

Which protein of the complement system binds to complement receptors on phagocytes, opsonizes pathogens, and removes immune complexes?

A

C3b

75
Q

What is C1s responsible for?

A

it cleaves C4 and C2

76
Q

The biological activities and the regulatory proteins of the lectin pathway and the classical pathway are ____.

A

the same

77
Q

___ initiates amplification via the alternative pathway, and binds C5 for cleavage by C2b.

A

C3b

78
Q

C4b2a is an active _____, which cleaves C3 into C3a and C3b, where C3b binds to the microbial surface.

A

C3 convertase

79
Q

A Type 1 allergic reaction elicits the _____ response.

A

wheal and flare

80
Q

What happens to the bacterial cell membrane when the MAC is completed and forms a pore?

A

depolarization

81
Q

What does C2b do?

A

it is the precursor to vasoactive C2 kinin

82
Q

How many subunits is C1q (part of the C1 complex) made up of?

A

6

83
Q

Which type of cells are attracted to cells that have been opsoninized?

A

phagocytic

84
Q

C3b acts as an ____.

A

opsonin

85
Q

Does the lectin pathway lead to the same kind of opsonization utilizing the C3 convertase as the classical and alternative pathways?

A

YES

86
Q

MASP-1 and MASP-2 are associated with ____.

A

carbohydrate binding

87
Q

The antigen:antibody complexes activate ____, which then targets _____.

A

C1q, C1r & C1s complex; C4 and C2

88
Q

Which proteins lead to local inflammation?

A

C5a, C3a

89
Q

What does C2a do?

A

it is the active enzyme of classical pathway C3/C5 convertase; cleaves C3 and C5

90
Q

C3b facilitates the removal of immune complexes, which means it activates the ______ components.

A

terminal complement

91
Q

C1 esterase inhibitors block angioedema on two levels; at ___ and ___.

A

Factor XIIa/Plasmin; Kallikrein

92
Q

After binding of the C1 complex and immunoglobulin, a conformational change results for ____.

A

C1r (which then goes on to cleave C1s)

93
Q

The redness of skin resulting from the dilation of blood vessels is called ____.

A

flare

94
Q

Complement-mediated endothelial cell injury creates a ____ state.

A

prothrombotic

95
Q

What do mast cells release during degranulation?

A

histamine

96
Q

Which molecule polymerizes on the C5b678 complex to form a pore on the membrane?

A

C9

97
Q

The addition of C3b to the C3 convertase produces ___.

A

C5 convertase (C3b2Bb)

98
Q

The classical pathway, lectin pathway, and alternative pathway all converge at what enzyme?

A

C3 convertase

99
Q

C4a ____ the opsonization process, whereas C3b ____ it.

A

initiates; amplifies

100
Q

What happens when C5a binds to the CR1 receptor on the cell membrane of a macrophage?

A

the macrophage will be activated and can phagocytose the bacterium

101
Q

CD59 (protectin) prevents formation of _____ and is widely expressed on host cell membranes.

A

membrane attack complex (MAC)

102
Q

C3bBb is a __ convertase and C3b2Bb is a __ convertase.

A

C3; C5

103
Q

The complement system becomes activated ____ of a prior adaptive immune system.

A

independently

104
Q

C3 gets cleaved into ___ and ___. What do each of the subunits do?

A

C3a (recruits phagocytes)

C3b (tags bacterium for destruction)

105
Q

DAF inhibits the formation of C3 complement components, thereby preventing the formation of ____ in the cell membrane.

A

complement-mediated pores

106
Q

C3b starts the opsonization process by _____ it.

A

amplifying

107
Q

The complement system and activation of complement is part of the ____ immune system.

A

innate

108
Q

Which opsonizing antigen has the most important opsonizing activity?

A

C3b

109
Q

The ____ pathway is homologous to the classical pathway, but uses opsonins, mannose-binding lectin (MBL), and ficolin instead of C1q.

A

Lectin Pathway

110
Q

The membrane protein that displaces Bb from C3b and C2a from C4b is called _____.

A

decay-accelerating factor (DAF)

111
Q

The adaptive immune system contains genetically encoded _____ that produce a variety of proteins that can recognize specific antigens.

A

proteins

112
Q

What do the terminal complement components do?

A

form the membrane-attack complex, lyse certain pathogens and cells

113
Q

The C4b2a convertase leads to the C3 convertase, which can lead to the production of the _____.

A

C5 convertase

114
Q

C2 gets cleaved into ___ and ___ by ____.

A

C2a; C2b; C1s

115
Q

Why is the alternative pathway activated at a low level?

A

because C3 is mildly unstable in an aqueous environment, spontaneous C3 hydrolysis occurs (breakdown of thioester bond)

116
Q

What are the two major functions of the complement system?

A

1) alters the membrane of pathogens + cellular debris (opsonization) to promote removal
2) enhances the inflammatory response that promote activation or migration of WBCs to site

117
Q

C5b binds __ and __ to form the ____ complex.

A

C6; C7; C5b67

Biochemistry (17 decks)

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