48-Cytokines Flashcards Preview

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Flashcards in 48-Cytokines Deck (44)
1

What is a cytokine?

proteins released by cells that participate in the immune response

2

How is cytokine expressed?

released extracellularly or expressed on surface of the cell

3

How are cytokines recognized?

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

4

what are the functions of cytokines in the immune response?

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

5

how do cytokines act?

autocrine, paracrine, endocrine

6

what is pleiotropy?

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

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

7

what is redundancy?

cytokines have the same action
IL2, 4, 5 do proliferation

8

what is synergy?

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

9

what is antagonism?

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

10

How is a cell fate decided?

cells integrate signals from many cytokines

11

what are the phases of sepsis?

cytokine storm and immune suppression?

12

what is the cytokine storm?

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

13

what is the immune suppression in sepsis?

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

14

cytokine treatments for sepsis

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

15

what are the 7 cytokine families

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

16

how are the cytokine families delineated

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

17

Growth factor family receptor

tyrosine kinase domains

18

growth factor family action

increased tyrosine phosphorylation signaling, immune cell differentiation

19

TGF-B receptor

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

20

TGF-B action

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

21

IL-1 Family receptor

TIR domain, binding of MyD88

22

IL-1 family action

MyD88 induces downstream signaling to activation NF-kB for inflammation

23

What does IL-1Ra do?

inhibit IL-1

24

TNF family receptor

TRAF and TRADD

25

TNF family action

TRAF is inflammatory
TRADD does apoptosis

26

What does TNF alpha and TNFR1 (receptor) do?

part of TNF family that can be inflammatory or do apoptosis

27

IL-17 Family receptor

TLR and TNF

28

IL-17 family action

dimerization and bind ACT1 which interacts with TRAF for inflammation

29

Chemokine family receptor

7 transmembrane g protein coupled receptor

30

chemokine family action

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

31

what are the functions of chemokine receptors

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

Classical cytokine family receptor

JAK/STAT, heterodimeric or trimeric

33

Classical cytokine family action

activation of JAK kinases to phosphorylate STAT, lots of functions

34

Type I Cytokine

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

differentiation, homeostasis, activation, suppression

35

Type II Cytokine

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

36

Three main classes of drugs targeting cytokine function

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

37

How do recombinant cytokines work

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

38

what is the exception to recombinant cytokines?

anakinra

39

how does anakinra work?

IL-1Ra which inhibits IL-1

40

what is the problem with recombinant cytokines

very powerful and substantial side effects

41

how do antibodies targeting cytokines work?

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

42

what is the problem is antibody cytokine drugs?

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

43

how do small molecule inhibitors work?

inhibit JAK/STAT

44

what are the problems with small molecule inhibitors?

increased infection, cancer, thrombocytopenia