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Immunology > 48-Cytokines > Flashcards

48-Cytokines Flashcards

1
Q

What is a cytokine?

A

proteins released by cells that participate in the immune response

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2
Q

How is cytokine expressed?

A

released extracellularly or expressed on surface of the cell

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3
Q

How are cytokines recognized?

A

unique receptors in surface of immune cells. activation of receptor results in changes in the function

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4
Q

what are the functions of cytokines in the immune response?

A 
hematopoiesis
chemotaxis
inflammation
antiviral response (interferons)
immune cell activation
suppression
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5
Q

how do cytokines act?

A

autocrine, paracrine, endocrine

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6
Q

what is pleiotropy?

A

a single cytokine has more than 1 function depending on the cell it targets

B cell-activation, proliferation, differentiation
thymocyte-proliferation
mast cell-proliferation

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7
Q

what is redundancy?

A

cytokines have the same action

IL2, 4, 5 do proliferation

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8
Q

what is synergy?

A 
cytokines act together for a response
IL4 and 5 induce class switch to IgE
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9
Q

what is antagonism?

A 
cytokines inhibit one another
Il4 and IFNy block class switch to IgE
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10
Q

How is a cell fate decided?

A

cells integrate signals from many cytokines

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11
Q

what are the phases of sepsis?

A

cytokine storm and immune suppression?

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12
Q

what is the cytokine storm?

A

1st phase in sepsis, driven by release of inflammatory cytokines

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13
Q

what is the immune suppression in sepsis?

A

2nd phase, days to weeks after onset, immunosuppressive cytokines released. this phase is resolved with elimination of infection or death

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14
Q

cytokine treatments for sepsis

A

most have failed. have not shown and increase in survival and have worsened death

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15
Q

what are the 7 cytokine families

A 
growth factory family
TGF-B
IL-1 
TNF
IL-17
chemokine
classical
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16
Q

how are the cytokine families delineated

A

by their receptor which have distinct signaling pathway. signaling pathway defines the treatment for cytokine

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17
Q

Growth factor family receptor

A

tyrosine kinase domains

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18
Q

growth factor family action

A

increased tyrosine phosphorylation signaling, immune cell differentiation

19
Q

TGF-B receptor

A

serine/threonine kinase domains, tetramerization of 2 type 1 and 2 type 2 for phosphorylation of SMAD proteins

20
Q

TGF-B action

A

inhibit immune cell function, t cell differentiation, antibody production, promote tissue repair

21
Q

IL-1 Family receptor

A

TIR domain, binding of MyD88

22
Q

IL-1 family action

A

MyD88 induces downstream signaling to activation NF-kB for inflammation

23
Q

What does IL-1Ra do?

A

inhibit IL-1

24
Q

TNF family receptor

A

TRAF and TRADD

25
Q

TNF family action

A

TRAF is inflammatory

TRADD does apoptosis

26
Q

What does TNF alpha and TNFR1 (receptor) do?

A

part of TNF family that can be inflammatory or do apoptosis

27
Q

IL-17 Family receptor

A

TLR and TNF

28
Q

IL-17 family action

A

dimerization and bind ACT1 which interacts with TRAF for inflammation

29
Q

Chemokine family receptor

A

7 transmembrane g protein coupled receptor

30
Q

chemokine family action

A

activation of small molecular weight g proteins, chemotaxis (migration of immune cells)

31
Q

what are the functions of chemokine receptors

A

inflammatory: movement towards infection
homeostatic: movement before an infection during homeostasis
atypical: silent and act as negative regulators
viral: allow pathogens to modulate immune responses

32
Q

Classical cytokine family receptor

A

JAK/STAT, heterodimeric or trimeric

33
Q

Classical cytokine family action

A

activation of JAK kinases to phosphorylate STAT, lots of functions

34
Q

Type I Cytokine

A

Hemopoietin, conserved structural elements
Conserved cysteines, conserved WSXWS, conserved y, conserved B, conserved gp130

differentiation, homeostasis, activation, suppression

35
Q

Type II Cytokine

A

Interferon
conserved cysteines, use distinct pools of JAK and STAT
antiviral responses

36
Q

Three main classes of drugs targeting cytokine function

A

actual cytokine: EPO
antibody inhibitors of cytokines (anti-TNF)
small molecule drugs (anti-JAK kinase)

37
Q

How do recombinant cytokines work

A

15 recombinations

enhance immune function (interferon a, b, y, epo, il-2, il-11, G-CSF, GM-CSF)

38
Q

what is the exception to recombinant cytokines?

A

anakinra

39
Q

how does anakinra work?

A

IL-1Ra which inhibits IL-1

40
Q

what is the problem with recombinant cytokines

A

very powerful and substantial side effects

41
Q

how do antibodies targeting cytokines work?

A

treat rheumatic disease, target IL-6, Blys, TNF-a, interferon-a

42
Q

what is the problem is antibody cytokine drugs?

A

increased infection, expensive, not as dangerous because of redundancy and low level activation

43
Q

how do small molecule inhibitors work?

A

inhibit JAK/STAT

44
Q

what are the problems with small molecule inhibitors?

A

increased infection, cancer, thrombocytopenia

Immunology (19 decks)

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