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Immunology > Complement System (6) > Flashcards

Complement System (6) Flashcards

1
Q

What is complement?

A

a group of serum and cell surface proteins activated by factors such as:
the combination of antigen and antibody

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2
Q

What does complement result in?

A

the generation of enzyme cascades that have a variety of biological consequences including cell lysis and opsonization

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3
Q

What are the 3 complement pathways?

A

classical pathway
alternative pathway
MB-lectin pathway

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4
Q

The classical pathway is [innate/adaptive]. Why?

A

adaptive
uses antibody + C1q
q: binds to antibody

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5
Q

MB-lectin pathway is [innate/adaptive]. Why?

A

innate
does not involve antibodies

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6
Q

Alternative pathway is [innate/adaptive]. Why?

A

innate
does not involve antibodies

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7
Q

What is the active form of the enzyme cascade?

A

C3b

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8
Q

C3a causes ______

A

inflammation

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9
Q

C3b causes ______ & ______

A

opsonization
phagocytosis

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10
Q

C5a causes _________

A

inflammation

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11
Q

C6-9 causes ______

A

lysis of microbe

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12
Q

What combines and forms C3 convertase to split C3 into C3b and C3a in the classical and lectin pathways?

A

C4b + 2b

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13
Q

In the alternative pathway, what combines and forms C3 convertase?

A

C3b + Bb

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14
Q

What is C2b?

A

a serine protease functioning as an active enzyme of C3 and C5 convertases

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15
Q

What initiates the classical pathway?

A

C1

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16
Q

C4[a/b] binds to C2 for cleavage by C1s

A

C4b

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17
Q

What initiates the lectin pathway? What does it do?

A

MBL
binds to terminal mannose residues of microbial carbohydrates
MBL-associated protease activates C4 & C2, as in the classical pathway

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18
Q

C3b is a component of C3 and C__ convertases

A

C5

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19
Q

What is factor B, or Bb?

A

Bb is a serine protease
the active enzyme of C3 and C5 convertases

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20
Q

What does C5b do?

A

initiates assembly of the membrane attack complex (MAC)

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21
Q

What are components of the membrane attack complex (MAC)?

A

C6-C9

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22
Q

Complement activation causes what sorts of things to happen?

A

altered membranes
inflammation
bacterial lysis
opsonization
mast cell degranulation
neutrophil chemotaxis
phagocytosis
etc

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23
Q

How is the classical pathway initiated?

A

when a complement-fixing antibody (IgM or IgG) binds antigen

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24
Q

The binding site for the complement on Fc portion of the antibody [closes/opens] up when the antibody is bound to the antigen

A

opens

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25
Q

T/F: The classical pathway occurs in a primary response

A

FALSE - does not

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26
Q

How is the alternative pathway initiated?

A

by C3b binding on the CELL WALL of pathogens

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27
Q

In the alternative pathway, _____ is the most abundant complement protein in the blood

A

C3

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28
Q

In the alternative pathway, ____ spontaneously breaks down to C3a and C3b

A

C3

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29
Q

In the alternative pathway, ____ binds to mammalian cells but is quickly inactivated

A

C3b

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30
Q

T/F: In the alternative pathway, adaptive immunity is not required for this pathway to be initiated

A

TRUE - part of innate immunity

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31
Q

What is the MB-Lectin pathway initiated by?

A

soluble pattern recognition molecules (PRR) that bind to carbohydrates on microbe SURFACES

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32
Q

In the MB-Lectin pathway, once PRRs bind to carbohydrates on microbe surfaces, this activates enzymes that activate ______

A

complement

33
Q

In the MB-Lectin pathway, adaptive immunity is not required for this pathway to be initiated

A

TRUE

34
Q

T/F: Mammalian cells do not have mannose on their surface. MBL pathway is then initiated on microbes but not self-cells

A

TRUE

35
Q

You need [1/2] molecules for IgG and [1/2] for IgM to bind to C1 in the classical pathway

A

IgG: 2
IgM: 1 (is a pentameter which is same conformation for C1 to bind)

36
Q

In the classical pathway, when the antibody binds the antigen, there is a _______ change in the _____ portion of the antibody which allows for C[1/2/3] to bind to the Antigen-antibody complex

A

conformational
Fc
C1

37
Q

How many Fc binding sites must there be for C1 to bind?

A

2!
so 2 molecules IgG
and 1 molecules IgM required for initiation

38
Q

[IgG/IgM] is more efficient at activating the classical pathway

A

IgM (because only 1 molecule required)

39
Q

Two IgG molecules in ______ are required to activate C1

A

close proximity

40
Q

In the classical pathway, activated C1 cleaves C[2/3/4] into _____ and ______

A

C4
C4 —> C4a + C4b

41
Q

In the classical pathway, C4b binds to a membrane, and _____ binds to this membrane-bound C4b

A

C2

42
Q

In the classical pathway, activated C1 cleaves C[2/3/4] when it is bound to C4[a/b], leading to the formation of _______

A

C2
C4b
C4b2b

43
Q

What is the classical pathway C3 convertase?

A

C4b2b

44
Q

In the classical pathway, C3 convertase, ie C4b2b, cleaves C___ into ____ & ______

A

C3
C3 —> C3a + C3b

45
Q

What is opsonization? Give an example of an opsonin

A

coating of surfaces of pathogens with C3b
C3b

46
Q

C3b binds C___ in the classical pathway

A

C5

47
Q

When C4bC2b cleaves C__, it leads to the initiation of the terminal pathway in the classical pathway

A

C5

48
Q

In the alternative pathway, C3 spontaneously breaks down into ____ and _____

A

C3a
C3b

49
Q

C3b’s reactive _____ will covalently bind to cell SURFACES

A

carbonyl group

50
Q

In the alternative pathway, what binds to Factor B?

A

C3b

51
Q

In the alternative pathway, Factor D can cleave ____ bound to _____

A

Factor B
C3b

52
Q

In the alternative pathway, _____ is the C3 convertase

A

C3bBb

53
Q

What is a soluble pattern recognition molecule (PRR) in the MBL-pathway?

A

mannose binding lectin

54
Q

What is mannose on microbes?

A

a PAMP (pathogen associated molecular pattern)

55
Q

What binds to mannose on microbes?

A

MBL

56
Q

Bound MBL activates _______, which has similar activity to C1

A

MASP-2 (MBL-associated serine protease)

57
Q

In the MBL pathway, what cleaves C4 that initiates the cascade?

A

MASP-2

58
Q

Cleavage of C__ initiates the terminal pathway

A

C5

59
Q

T/F: The terminal complement pathway is the same for all 3 pathways

A

TRUE

60
Q

Are enzymes involved in the terminal pathway?

A

No

61
Q

What does initiation of the terminal pathway eventually lead to?

A

formation of the membrane-attack complex (MAC)

62
Q

When C5 binds to C3b, it exposes a site on C5[a/b] that can bind C__ and C__

A

C5b
C6
C7

63
Q

In the terminal pathway, C______ binds C8 and inserts into the membrane

A

C5b67

64
Q

In the terminal pathway, _____ damages the membrane and induces polymerization of C9

A

C5b678

65
Q

In the terminal pathway, 12-18 molecules of C9 polymerize and form a _______

A

transmembrane pore

66
Q

In the terminal pathway, what is the result of C9 forming a transmembrane pore?

A

cell lysis and death

67
Q

Classical activation is regulated by _____ which blocks interaction with C1 protein and antibody

A

C1-INH

68
Q

Alternate activation is controlled by ____, _____, and _____

A

Factor H (co-factor with I)
Factor I (co-factor with H)
CD59

69
Q

What do factors H and I do to regulate the alternative pathway?

A

mediate inactivation of C3

70
Q

What does CD59 in the alternative pathway regulate?

A

block formation of membrane

71
Q

What is another way of regulating complement pathways?

A

substrate modulation

72
Q

What are some biological consequences of complement activation?

A
73
Q

What are the functions of complement?

A

phagocytosis and killing of microbe
osmotic lysis of microbe from complement=mediated cytolysis
destruction of microbes by leukocytes from stimulation of inflammatory reactions

74
Q

______ are found in normal serum

A

Complement proteins

75
Q

The innate complement pathways are activated by recognizing ______

A

pathogen-associated molecular patterns (PAMPs)

76
Q

The classical pathway is activated by ______

A

antibodies bound to foreign antigens

77
Q

The complement component, especially ____, bind COVALENTly to invading microbes and opsonize them

A

C3b

78
Q

Complement components may form a terminal complemental complex and ____ ______ in microbes

A

punch holes

79
Q

The complement system triggers inflammation through the release of the potent chemoattractant _____

A

C5a

Immunology (36 decks)

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