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IMSE > Week 8 Lec: Complement System > Flashcards

Week 8 Lec: Complement System Flashcards

1
Q

It is a complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to enhance host defense mechanisms against foreign cells.

A

Complement

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2
Q

Complement is a complex series of more than ___ soluble and cell-bound proteins.

A

30

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3
Q

Complement systems is also called?

A

complement pathway

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4
Q

Complement is a complex series of more than 30 soluble and cell-bound proteins that interact in a very specific way to?

A

enhance host defense mechanisms against foreign cells

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5
Q

Complement is a heat-_____ substance.

A

labile

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6
Q

A termed “Complement” was given by?

A

Paul Erlich (1980’s)

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7
Q

In 1919, __________ was awarded a Noble Prize for elucidating the nature of complement.

A

Jules Bordet

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8
Q

In _____, Jules Bordet was awarded a Noble Prize for elucidating the nature of complement.

A

1919

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9
Q

Effects of complement activation - Complement activation promotes?

A
  • Activation of immune system
  • Opsonization (C3b, C4b, C5b) and
  • eventually result to LYSIS of Foreign cells and Immune complexes.
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10
Q

Chronic Activation of complement system leads to?

A

inflammation and tissue damage

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11
Q

Complement pathway plays an essential role as a?

A

pro-inflammatory agent

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12
Q

Acute Phase Reactants are produced primarily by __________ within _____ hours in response to an increase in certain intracellular signaling polypeptides called __________.

A

hepatocytes/liver parenchymal cells; 12-24; cytokines

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13
Q

2 major acute phase reactants?

A

Serum amyloid A and C-reactive protein

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14
Q

C-reactive protein is for?

A

opsonization and for complement activation

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15
Q

C-reactive protein response time?

A

6-10 hrs

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16
Q

Serum amyloid A is for?

A

removal of cholesterol

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17
Q

Acute Phase Reactants increase rapidly by _____ during infection.

A

25%

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18
Q

True or false: APRs are normal serum constituents.

A

True

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19
Q

Most plasma complement proteins are synthesized in the?

A

liver

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20
Q

Most plasma complement proteins are synthesized in the liver, except?

A

C1

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21
Q

C1 is produced by?

A

Epithelial cells and Factor D (made in Adipose tissue)

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22
Q

Plasma complement proteins are released in inactive precursors called?

A

zymogens

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23
Q

Zymogens, when triggered with antigenic stimulation, will convert into active form called?

A

Holoenzymes

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24
Q

The complement system can be activated in three different ways?

A
  1. Classical Pathway
  2. Alternative pathway
  3. Lectin Pathway
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25
Q

Pillemer and colleagues discovered an antibody-dependent pathway in the 1950s, and this plays a major role as a natural defense system.

A

Classical Pathway

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26
Q

How many proteins does the classical pathway have?

A

9

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27
Q

The Classical Pathway is initiated by?

A

C1

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28
Q

Alternative pathway is formerly known as?

A

Properdin system

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29
Q

True or false: Alternative pathway is antibody-independent.

A

True

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30
Q

Major constituent of Lectin Pathway?

A

mannose- (or mannan-) binding lectin (MBL)

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31
Q

Classical pathway involves proteins that are triggered by ____________ combination.

A

Antigen-antibody

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32
Q

True or false: Classical Pathway/Cascade is antibody-dependent.

A

True

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33
Q

True or false: Not all immunoglobulins are able to activate the Classical Pathway.

A

True

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34
Q

Immunoglobulins that can participate in complement fixation?

A

IgM and IgG

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35
Q

Immunoglobulin most efficient in complement fixation?

A

IgM, because it has multiple binding sites

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36
Q

Which IgG subtypes can participate in complement fixation?

A

IgG3, IgG1, and IgG2 (in order from most to least efficient)

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37
Q

How can the IgG activate complement fixation?

A

2 IgG molecules should be attached to antigen within 30-40 nanometers

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38
Q

Stages of Complement Activation in Classical Pathway?

A
  1. Recognition stage
  2. Activation stage
  3. Formation of MAC
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39
Q

C4, C2 and C3 is known collectively as the?

A

activation unit

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40
Q

In the Recognition Unit, the first complement component to bind is?

A

C1

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41
Q

C1 consists of three subunits?

A

C1q, C1r, C1s

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42
Q

The C1 complex is made up of?

A
  • one Clq subunit
  • two each of the C1r and C1s subunits
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43
Q

In the Recognition Unit, the _____ and _____ subunits generate enzyme activity to begin the cascade.

A

C1r and C1s

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44
Q

It is composed of six strands that form six globular heads with a collagen-like tail portion.

A

C1q

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45
Q

C1q “recognizes” the ________________ of two adjacent antibody molecules.

A

fragment crystallizable (FC) region

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46
Q

C1q binds to the __________ portion of the antibody.

A

Fc

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47
Q

At least _____________ of C1q must be bound to initiate the classical pathway.

A

two of the globular heads

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48
Q

Recognition Unit process?

A
  1. Fc region is bonded with C1q
  2. Activation of C1r
  3. Cleaves the thioester bond of C1s
  4. Activates C1s
  5. End of recognition stage
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49
Q

C1q binds to Fc region of the immunoglobulins. This binding occurs specifically at the?

A

Ch2 region for lgG and at the Ch3 region for IgM

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50
Q

End product of Activation Unit is the formation of?

A

C5 Convertase

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51
Q

C4 and C2 must be close enough to _____ for cleavage to occur.

A

C1s

52
Q

C2 should be at least ___ radius of bound C1s.

A

60nm

53
Q

C4 should be at least ___ of bound C1s.

A

40nm

54
Q

____ is the second-most-abundant complement protein.

A

C4

55
Q

C4 cleaves by C1s to form?

A

C4a and C4b

56
Q

C4b must bind to protein or carbohydrate within a few seconds, or it will react with water molecules to form ________, which is rapidly degraded.

A

iC4b

57
Q

In the Activation Unit, the next component to be activated after C4 is?

A

C2

58
Q

C2 gene is closely associated with the gene for _________ on chromosome ___ in the _______________.

A

factor B (alternative pathway); chromosome 6; major histocompatibility complex (MHC class III)

59
Q

When combined with C4b in the presence of __________, C2 is cleaved by C1s to form C2a and C2b.

A

magnesium ions

60
Q

C2a binds to C4b to form?

A

C3 Convertase

61
Q

C3 Convertase is also known as?

A

C4b2a

62
Q

True or false: C4b2a (C3 Convertase) is very stable.

A

False. This complex is not very stable.

63
Q

C4b2a (C3 Convertase) half-life is estimated to be between?

A

15 seconds to 3 minutes

64
Q

If binding of C4b2a (C3 Convertase) does occur, C3 is cleaved into two parts, namely?

A

C3a and C3b

65
Q

What is the most significant step in the entire process of complement activation?

A

cleavage of C3 component to form C3a and C3b

66
Q

Functions of C3b?

A
  • Major function is for the formation of the MAC.
  • Another function is that, C3b acts as an opsonin → Macrophages have specific receptors for this complement. Thus, enhance phagocytosis.
67
Q

If C3b is bound within 40 nm of the C4b2a, then this creates a new enzyme known as?

A

C5 convertase

68
Q

C5 convertase denotes the start of?

A

MAC

69
Q

C3b is bound within ______ of the C4b2a to create the enzyme C5 convertase.

A

40 nm

70
Q

These cause increased vascular permeability.

A

Anaphylatoxins

71
Q

What happens when there is increased permeability due to anaphylatoxins?

A
  • release of histamine from basophils and mast cells
  • contraction of smooth muscle
72
Q

Proteins involved in increased permeability?

A

C3a, C4a, and C5a

73
Q

Cleaving of C5 into C5a and C5b by C5 convertase at another site on the cell membrane constitutes the beginning of the?

A

membrane attack complex

74
Q

True or false: C5b is extremely labile.

A

True

75
Q

True or false: C5b is rapidly inactivated when no binding of C6 occurs.

A

True

76
Q

C6 binds to C5b to form?

A

C5b6

77
Q

C7 binds to C5b6 to form?

A

C5b67

78
Q

This forms a trimolecular complex that has a high affinity for lipid constituents of the cell membrane.

A

C5b67

79
Q

C8 binds to C5b67 to form?

A

C5b678

80
Q

_____ and _____ interact with the cell membrane to form a small hole in the membrane.

A

C7 and C8

81
Q

____ is inserted into the lipid bilayer of the cell membrane.

A

C8

82
Q

What happens after C8 is inserted into the lipid bilayer of the cell membrane?

A

Pore formation → Lysis of cell starts on this stage → Contents of the cell leaks (potassium, amino acids, ribonucleotides)

83
Q

Pores formed are small and are able to?

A

lyse RBC but not nucleated cells

84
Q

C9 binds to C5b678 which indicates?

A

complete lysis of the cell

85
Q

Complete MAC unit?

A

C5b6789

86
Q

Alternative pathway was originally named for the protein?

A

properdin

87
Q

Properdin is a constituent of normal serum with a concentration of approximately?

A

5 to 15 μg/mL

88
Q

Now it is known that properdin does not initiate the alternative pathway but rather?

A

stabilizes the C3 convertase formed from the activation of other factors

89
Q

In addition to properdin, the serum proteins that are unique to the alternative pathway include?

A

factor B and factor D

90
Q

C1, C2, and C4, found in the classical pathway, are not used at all in what system?

A

Alternative Pathway

91
Q

Triggering substances for the alternative pathway include?

A

Bacteria, fungi, viruses, tumor cell lines and some parasites such as Trypanosomes

92
Q

Immunoglobulin that triggers the Alternative Pathway?

A

IgA

93
Q

Major factor in complement system (alternative and classical pathway)?

A

C3

94
Q

Alternative Pathway: Factor B is analogous to?

A

C2

95
Q

Alternative Pathway: Factor B binds to?

A

activated C3 (C3b)

96
Q

Alternative Pathway: Functions of Factor D?

A
  • Cleaves factor B that are bounded to C3b
  • Cleaves factor B to Bb and Ba
  • Bb remains attached to C3b, forming C3bBb
97
Q

Alternative Pathway: Functions of C3bBb?

A
  • Cleaves additional C3 into C3a and C3b
  • Some C3b attaches to cellular surfaces and acts as a binding site for more Factor B
98
Q

Alternative Pathway: C3bBb is stabilized by ______, which increases its half-life from _____ to _____.

A

properdin; 90 seconds to several minutes

99
Q

Alternative Pathway: Some C3b binds to C3bBb to form the?

A

C3bBb3b (C3bBb3bP) complex

100
Q

C3bBb3b (C3bBb3bP) complex has high affinity to?

A

C5 convertase

101
Q

Alternative Pathway: It cleaves C5 into C5a and C5b.

A

C3bBb3b (C3bBb3bP) complex

102
Q

Alternative Pathway: _____ is the first part for the formation of the MAC.

A

C5b

103
Q

MBL is considered an?

A

acute phase protein

104
Q

MBL is produced in the?

A

liver

105
Q

MBL is normally present in the?

A

serum

106
Q

MBL increases during an?

A

initial inflammatory response

107
Q

Lectins are proteins that bind to?

A

carbohydrates

108
Q

This pathway provides an additional link between the innate and acquired immune response.

A

Lectin Pathway

109
Q

Lectin Pathway provides an additional link between the innate and acquired immune response because it involves nonspecific recognition of ________that are common constituents of microbial cell walls and that are distinct from those found on human cell surfaces.

A

carbohydrates

110
Q

The structure of MBL is similar to that of C1q, and it is associated with three MBL-associated serine proteases (MASPs)?

A

MASP-1, MASP-2, and MASP-3

111
Q

MASP-1 & 3 function?

A

still unclear

112
Q

MASP-2 function?

A

active role in cleaving C4 and C2 with C1s

113
Q

MASP-2 is homologous to?

A

C1s

114
Q

Lectin Pathway: Once C4 and C2 are cleaved, the rest of the pathway is identical to the?

A

Classical Pathway

115
Q

It inactivates C1 and MASP-2.

A

C1 inhibitor or C1INH

116
Q

It is a glycoprotein with a molecular weight of 105,000 that inhibits activation at the first stages of both the classical and lectin pathways.

A

C1 inhibitor or C1INH

117
Q

C1 inhibitor or C1INH is a glycoprotein with a molecular weight of?

A

105,000

118
Q

The main role of C1 inhibitor or C1INH is to inactivate C1 by ______________.

A

binding to the active sites of C1r and C1s; C1r and C1s become instantly and irreversibly dissociated from C1q

119
Q

True or false: After the action of the C1 inhibitor or C1INH, C1q remains bound to antibody, but all enzymatic activity ceases.

A

True

120
Q

C3 convertase is inhibited by four main regulators?

A
  • C4b-binding protein (C4BP)
  • Complement receptor 1 (CR1)
  • Membrane cofactor protein (MCP)
  • Decay accelerating factor (DAF)
121
Q

Binds to Factor I then inactivates the C4b resulting in the dissociation of C4b from the C4b2a complex, causing the classical pathway to stop and not able to continue the pathway.

A

C4b-binding protein (C4BP)

122
Q

Also known as CD35; binds to C3b or C4b, then it is degraded by factor I.

A

Complement receptor 1 (CR1)

123
Q

Main function is it acts as a receptor on platelets and RBCs which helps mediate transport of C3b-coated immune complexes on the liver and spleen.

A

Complement receptor 1 (CR1)

124
Q

Also known as CD46. Most efficient cofactor for Factor I-mediated cleavage of C3b.

A

Membrane cofactor protein (MCP)

125
Q

It also serves as cofactor for Factor I in cleaving the C4b; not as efficient as the C4bB (most efficient in inhibiting the activity of the classical pathway).

A

Membrane cofactor protein (MCP)

126
Q

Also known as CD55. Dissociates the C3 convertase by cleaving the C3b or C4b or both.

A

Decay accelerating factor (DAF)

127
Q

3rd main receptor and has a wide tissue distribution. Capable of dissociating both classical and alternative pathway C3 convertases.

A

Decay accelerating factor (DAF)

IMSE (9 decks)

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