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Veterinary Immunology > Lecture 6 - Complement System > Flashcards

Lecture 6 - Complement System 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

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 pathways to activate complement

A
  1. classical
  2. alternative
  3. MB-lectin
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4
Q

When is the classical pathway initiated

A

when a complement fixing antibody (IgM, IgG) binds
antigen

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5
Q

What immunities are involved in the classical pathway

A

innate AND adaptive

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6
Q

Does the classical pathway occur in a primary response

A

YES

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7
Q

What happens in the classical pathway after the antibody is bound to antigen?

A

binding site for complement on Fc portion of the antibody opens up

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8
Q

What is the alternative pathway initiated by

A

C3b binding on the cell wall of pathogens

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9
Q

What is the most abundant complement protein in the blood

A

C3

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10
Q

What does C3 spontaneoulsy break down to in the alternative pathway

A

C3a and C3b

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11
Q

What happens when C3 b binds to mammalian cells

A

it is quickly innactivated

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12
Q

What immunity is the alternative pathway part of

A

INNATE

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13
Q

What immunity is not required for the alternative pathway to be innitiated

A

ADAPTIVE

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14
Q

What is the MB-lectin pathway initiated by

A

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

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15
Q

What does MB-lectin pathway activate

A

enzymes that activate complement

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16
Q

What immunity is MB-lectin pathway part of

A

INNATE

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17
Q

What immunity is not required to activate the MB-lectin pathway

A

ADAPTIVE

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18
Q

Why is MBL pathway initiated on bacteria cells but not self-cells

A

mammalian cells do not have mannose on their surface

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19
Q

Where do the three complement pathways differ

A

initiation of the cascade

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20
Q

Where are the three complement pathways the same from

A

C3 through the terminal pathway and formation of the membrane attack complex (MAC)

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21
Q

What complement pathways are part of the innate defense

A

Alternative and MBL pathways

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22
Q

What pathways require adapte immune response to initiate

A

classical pathway

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23
Q

What does classical pathway require

A

IgM and IgG

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24
Q

What BINDING initiaites the classical pathway

A

Ag-Ab binding

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25
Q

What happens after the Ab binds the Ag in the classical pathway

A

conformational change in the Fc portion of Ab that allows C1, the first protein of the complement cascade to bind to the Ag-Ab complex

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26
Q

Why is one IgM or two IgG required for initiation

A

there must be 2 Fc binding sites for C1 to bind

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27
Q

What is more efficient at activating the classical pathway of complement

A

IgM

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28
Q

How many IgM bound to Ag can initiate the classical complement cascade

A

ONE pentameric IgM

29
Q

How many IgG can activate C1 in the classical pathway

A

TWO IgG molecules in CLOSE PROXIMITY

30
Q

What does activated C1 cleave in the classical pathway

A

C4 into C4a and C4b

31
Q

What binding event occurs in the classical pathway after C1 cleaves C4?

A

C4b binds to a membrane and C2 binds to membrane bound C4b

32
Q

What does C1 do in the classical pathway after C4b binds to the membrane

A

cleaves C2 when it is bound to C4b, leading to formation of C4bC2b

33
Q

What is the C4b2b in the classical pathway

A

C3 convertase

34
Q

What is the classical pathway C3 convertase

A

C4b2b

35
Q

What does C3 convertase cleave in the classical pathway

A

3 into C3a and C3b

36
Q

What molecule in the classical pathway is an opsonin

A

C3b

37
Q

What are pathogens opsonized with in the classical pathway

A

C3b

38
Q

What leads to initiation of the terminal pathway

A

C3b binds C5 and C4bC2b cleaves C5

39
Q

ACTIVATION of the ALTERNATIVE pathway
1. C3 sponatneously breaks down into ___ and ____
2. C3b’s reactive carbonyl group will ______
3. ____ can bind to C3b
4. _____ can cleave Factor B bound to C3b
5. _____ is the alternative pathway C3 convertase

A
  1. C3a and C3b
  2. covalently bind to cell surfaces
  3. Factor B
  4. Factor D
  5. C3bBb
40
Q

What is the alternative pathway C3 convertase

A

C3bBb

41
Q

ACTIVATION of the MBL pathway
1. MBL is a _______
2. MBL binds to ______ on microbes
3. Bound MBL activates _______, which has similar activity to ____
4. MASP-2 cleaves ___ and the cascade is initiated

A
  1. soluble PRR
  2. mannose (a PAMP)
  3. MASP-2, C1
  4. C4
42
Q

What part of the complement cascade is the same for all 3 pathways

A

terminal complement pathway

43
Q

What initiates the terminal pathway

A

cleavage of C5

44
Q

What are not involved after initiation of the terminal pathway

A

enzymes

45
Q

What does initiation of the terminal pathway lead to formation of

A

membrane attack complex

46
Q

What occurs with the MAC when C5 binds to C3b

A

it exposes a site on C5b that can bind C6 and C7

47
Q

What occurs after the site on C5b that can bind C6 and C7 is exposed

A

C5b67 binds C8 and inserts into the membrane

48
Q

What occurs after C5b67 binds C8 and inserts into the membrane

A

C5b678 damages the membrane and induces polymerization of C9

49
Q

What is involved in polymerization of C9

A

12-18 molecules of C9 polymerize and form a transmembrane pore

50
Q

What is the result of polymerization of C9

A

lysis and cell death

51
Q

What is a regulator of classical activation

A

C1-INH

52
Q

What is a regulator of C3

A

CD59

53
Q

What is a regulator of the alternative pathway

A

Factor H

54
Q

What effect does C1 have onC2

A

NONE

55
Q

What effect does C1 have on C4b2

A

Cleaves into C4b2b and C2a

56
Q

What effect does D have on B

A

none

57
Q

What effect does D have on C3bB

A

cleaves into C3bBb and Ba

58
Q

What effect does C4b2b have on C5

A

none

59
Q

What effect does C4b2b have on C3b5

A

cleaves into C3b5b and C5a

60
Q

What biological consquence of complement activation does C2a have

A

increased vascular permeability

61
Q

What biological consquence of complement activation does C3a have

A

anaphylatoxin and microbial killing

62
Q

What biological consquence of complement activation does C3b have

A

immune regulation and opsonization

63
Q

What biological consquence of complement activation does C5a have

A

-neutrophil chemotaxis
-anaphylatoxin
-lysosomal enzyme secretion
-neutrophil activation
-increased vascular permeability
-smooth muscle contraction

64
Q

Overall result of opsonization and phagocytosis

A

phagocytosis and killing of microbe

65
Q

Overall result of complement-mediated cytolysis

A

osmotic lysis of microbe

66
Q

Overall result of stimulation of inflammatory reactions

A

destruction of microbes by leukocytes

67
Q

Complement proteins are found in _____

A

normal serum

68
Q

Complement components may form a terminal complement complex and _______

A

punch holes in microbes

Veterinary Immunology (20 decks)

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