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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
what is the mechanism of certolizumab pegol
it neutralizes membrane associated and soluble human TNFa
26
does certolizumab pegol fix complement
no
27
does certolizumab pegol cause ADCC
no
28
what kind of antibody is certolizumab pegol (what is the structure)
recombinant humanized anti TNFa Fab with polyethylene glycol
29
what kind of antibody is adalimumab
human monoclonal antibody
30
what kind of antibody is infliximab
chimeric
31
what is the structure of etarnecept
all human soluble receptor for TNF-a fused to the Fc of IgG
32
what is the mechanism of etarnecept + result
inhibits binding of TNF-a to its receptor competitively to block the inflammatory response
33
what happens to cells expressing TNFa with etarnecept
they die
34
what is the half life of etarnecept like compared to mAbs
short
35
what disease does TNF-a play a large role in
RA
36
how does TNF-a inhibitors compare to traditional disease modifying drugs
they are more effective
37
what is the role of IL-1
very important with inflammation and host response to infection
38
what happens to IL-1 in many diseases
it is deregulated
39
what are 2 important cells in autoimmune cells
monocytes and neutrophils
40
what are the 2 forms of IL-1
IL-1 alpha and beta
41
what do IL-1a and IL-1b do
trigger inflammation by binding to the same receptor
42
what are 2 examples of anti IL-1 therapies
rilonacept and anakinra
43
how does anakinra work
competes with IL-1
44
what is rilonacept (general)
anti IL-1
45
what is anakinra (general)
anti IL-1
46
what is anakinra used for
RA
47
what is rilonacept used for
auto-inflammatory syndromes
48
what is daclizumab
humanized mAb against CD25
49
what is IL2
main growth factor for activated T cells (stimulates clonal expansion and maturation)
50
what is an example of a humanized mAb against CD25
daclizumab
51
what is CD25
part of the IL2 receptor
52
what kind of cells express CD25 (and who doesnt)
activated T cells express high levels, rarely expressed in normal T cells
53
what is the mechanism of daclizumab
blocks IL2R resulting in inhibition of activated T cell proliferation
54
what kind of disease has daclizumab been used for
MS
55
what are interferons
widely expressed cytokines which are very strong
56
what are interferons key component of
innate immunity
57
what causes production of natural interferons
stimulation by viruses or microbial products -TLR activation activates genes
58
what kind of effects do interferons have
antiviral and growth inhibitory
59
what is our first line of defence against viral infection
interferons
60
besides viruses, what else do interferons surveille for
malignant cells
61
can viruses and cancer defend against interferons
yes, they have mechanisms to block its synthesis and action
62
what are the 3 types of interferons
type 1 INF-a type 2 INF-gamma type 3 INF-delta
63
what is the role of type 1 interferons
mounting a robust host response against viral infection
64
what is the role of type 2 interferons
mediate broad immune responses to pathogens other than viruses
65
what is the role of type 3 interferons
regulate antiviral response
66
what is the main thing that comes out of interferon receptor signalling
downstream pathways activate transcription factors
67
who produces type 1 interferons
all nucleated cells in response to viral or microbial infections
68
which type of interferons makes a robust response against viral infections
1
69
which cell types express type 1 interferons
nearly all cell types
70
do type 1 interferons play a role in autoimmunity
yes
71
what are type 1 interferons used for (therapy)
suppressing HCV and HBV infections
72
what cell types secrete INF-gamma
mostly by T cells and NK cells (also macrophages DC and B cells)
73
what mediates response to interferons gamma
cell specific expression of interferon stimulated genes
74
what does interferons gamma play an essential role in
autoimmunity
75
what is natalizumab
humanized mAb against adhesion molecule alpha4 integrin
76
what is alpha4 integrin
component of VLA4 expressed on activated lymphocytes, monocytes and other cells, role in adhesion
77
what is the mechanism of natalizumab
prevents interaction between VLA4 and its endothelial ligand vascular cell adhesion molecule
78
what is the cellular effect of natalizumab
prevents lymphocytes from crossing the BBB
79
what does natalizumab do to lymphocytes entering the BBB
prevents
80
what is omalizumab
Humanized mAb that targets IgE
81
what are the 2 mechanisms of omalizumab
sequester allergic IgE and downregulates FcR
82
how does omalizumab sequester allergic IgE
binds and prevents secreted IgE from binding to mast cells and basophils
83
what kind of disease is omalizumab best for
allergy
84
what are 4 things that omalizumab does
- binds to free IgE - decreases FcR expression - decreases mediator release - decrease inflammatory repsonse

PMCOL 344 (27 decks)

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