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PMCOL 344 > Immune-7 > Flashcards

Immune-7 Flashcards

1
Q

what are cytokines

A

short range protein mediators

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2
Q

what do cytokines regulate

A

immune response

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3
Q

what does early cytokine shape

A

the nature of immune response (beneficial or exaggerated)

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4
Q

what are 3 examples of things that cytokines do (biological processes) + which cytokines do it

A

T cell growth (IL-2), inflammation (TNF, IL-1) and inhibition of inflammation (IL-10)

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5
Q

what are 2 reason why cytokines are good potential therapeutic targets

A

because of their potency and they are extracellular molecules

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6
Q

what is a major problem with cytokines as therapeutic targets

A

there is considerable overlap in their functions (so you take one out, and another will yake over the function)

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7
Q

what is TNF-a (general)

A

a pleiotropic (many effects) cytokines with fundamental roles

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8
Q

what are 5 beneficial functions of TNFa

A
  • pathogen defence
  • develop lymphoid organ
  • resolve inflammation
  • tissue regeneration
  • immune regulation
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9
Q

what are 3 pathogenic functions of TNFa

A
  • triggering of inflammation
  • immune cell proliferation
  • tissue damage
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10
Q

which cells make TNFa in the periphery

A

pretty much all of them (macrophages, B, T, NK, DC, monocytes)

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11
Q

which cells make TNFa in the CNS (3)

A

microglia, neurons, astrocytes

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12
Q

what is TNFs production deregulation linked to

A

severe inflammation and autoimmune diseases

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13
Q

what are the 2 forms of TNFa

A

membrane bound and soluble

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14
Q

what does membrane bound TNFa do (general, where bind)

A

binds and signals to adjacent cells

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15
Q

what does soluble TNFa do (general, where bind)

A

can act in autocrine manner or can act on cells that are a bit farther away than with membrane bound

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16
Q

which receptors does TNFa bind to

A

type 1 and type 2 TNFRs

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17
Q

what are 3 antibodies against TNFa

A

infliximab, adalimumab, certolizumab pegol

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18
Q

what is a receptor fusion protein against against TNFa

A

etarnacept

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19
Q

what is etarnacept

A

receptor fusion protein against against TNFa

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20
Q

what is infliximab

A

antibodies against TNFa

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21
Q

what is adalimumab

A

antibodies against TNFa

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22
Q

what is certolizumab pegol

A

antibodies against TNFa

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23
Q

what is adalimumab specific for

A

TNFa - soluble and transmembrane

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24
Q

what is the mechanism of adalimumab

A

bind TNFa and suppresses formation of downstream inflammatory cytokines, reduce macrophage recruitment

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25
Q

what is the mechanism of certolizumab pegol

A

it neutralizes membrane associated and soluble human TNFa

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26
Q

does certolizumab pegol fix complement

A

no

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27
Q

does certolizumab pegol cause ADCC

A

no

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28
Q

what kind of antibody is certolizumab pegol (what is the structure)

A

recombinant humanized anti TNFa Fab with polyethylene glycol

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29
Q

what kind of antibody is adalimumab

A

human monoclonal antibody

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30
Q

what kind of antibody is infliximab

A

chimeric

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31
Q

what is the structure of etarnecept

A

all human soluble receptor for TNF-a fused to the Fc of IgG

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32
Q

what is the mechanism of etarnecept + result

A

inhibits binding of TNF-a to its receptor competitively to block the inflammatory response

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33
Q

what happens to cells expressing TNFa with etarnecept

A

they die

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34
Q

what is the half life of etarnecept like compared to mAbs

A

short

35
Q

what disease does TNF-a play a large role in

A

RA

36
Q

how does TNF-a inhibitors compare to traditional disease modifying drugs

A

they are more effective

37
Q

what is the role of IL-1

A

very important with inflammation and host response to infection

38
Q

what happens to IL-1 in many diseases

A

it is deregulated

39
Q

what are 2 important cells in autoimmune cells

A

monocytes and neutrophils

40
Q

what are the 2 forms of IL-1

A

IL-1 alpha and beta

41
Q

what do IL-1a and IL-1b do

A

trigger inflammation by binding to the same receptor

42
Q

what are 2 examples of anti IL-1 therapies

A

rilonacept and anakinra

43
Q

how does anakinra work

A

competes with IL-1

44
Q

what is rilonacept (general)

A

anti IL-1

45
Q

what is anakinra (general)

A

anti IL-1

46
Q

what is anakinra used for

A

RA

47
Q

what is rilonacept used for

A

auto-inflammatory syndromes

48
Q

what is daclizumab

A

humanized mAb against CD25

49
Q

what is IL2

A

main growth factor for activated T cells (stimulates clonal expansion and maturation)

50
Q

what is an example of a humanized mAb against CD25

A

daclizumab

51
Q

what is CD25

A

part of the IL2 receptor

52
Q

what kind of cells express CD25 (and who doesnt)

A

activated T cells express high levels, rarely expressed in normal T cells

53
Q

what is the mechanism of daclizumab

A

blocks IL2R resulting in inhibition of activated T cell proliferation

54
Q

what kind of disease has daclizumab been used for

A

MS

55
Q

what are interferons

A

widely expressed cytokines which are very strong

56
Q

what are interferons key component of

A

innate immunity

57
Q

what causes production of natural interferons

A

stimulation by viruses or microbial products -TLR activation activates genes

58
Q

what kind of effects do interferons have

A

antiviral and growth inhibitory

59
Q

what is our first line of defence against viral infection

A

interferons

60
Q

besides viruses, what else do interferons surveille for

A

malignant cells

61
Q

can viruses and cancer defend against interferons

A

yes, they have mechanisms to block its synthesis and action

62
Q

what are the 3 types of interferons

A

type 1 INF-a
type 2 INF-gamma
type 3 INF-delta

63
Q

what is the role of type 1 interferons

A

mounting a robust host response against viral infection

64
Q

what is the role of type 2 interferons

A

mediate broad immune responses to pathogens other than viruses

65
Q

what is the role of type 3 interferons

A

regulate antiviral response

66
Q

what is the main thing that comes out of interferon receptor signalling

A

downstream pathways activate transcription factors

67
Q

who produces type 1 interferons

A

all nucleated cells in response to viral or microbial infections

68
Q

which type of interferons makes a robust response against viral infections

A

1

69
Q

which cell types express type 1 interferons

A

nearly all cell types

70
Q

do type 1 interferons play a role in autoimmunity

A

yes

71
Q

what are type 1 interferons used for (therapy)

A

suppressing HCV and HBV infections

72
Q

what cell types secrete INF-gamma

A

mostly by T cells and NK cells (also macrophages DC and B cells)

73
Q

what mediates response to interferons gamma

A

cell specific expression of interferon stimulated genes

74
Q

what does interferons gamma play an essential role in

A

autoimmunity

75
Q

what is natalizumab

A

humanized mAb against adhesion molecule alpha4 integrin

76
Q

what is alpha4 integrin

A

component of VLA4 expressed on activated lymphocytes, monocytes and other cells, role in adhesion

77
Q

what is the mechanism of natalizumab

A

prevents interaction between VLA4 and its endothelial ligand vascular cell adhesion molecule

78
Q

what is the cellular effect of natalizumab

A

prevents lymphocytes from crossing the BBB

79
Q

what does natalizumab do to lymphocytes entering the BBB

A

prevents

80
Q

what is omalizumab

A

Humanized mAb that targets IgE

81
Q

what are the 2 mechanisms of omalizumab

A

sequester allergic IgE and downregulates FcR

82
Q

how does omalizumab sequester allergic IgE

A

binds and prevents secreted IgE from binding to mast cells and basophils

83
Q

what kind of disease is omalizumab best for

A

allergy

84
Q

what are 4 things that omalizumab does

A
  • binds to free IgE
  • decreases FcR expression
  • decreases mediator release
  • decrease inflammatory repsonse

PMCOL 344 (27 decks)

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