48-Cytokines

Question 1

What is a cytokine?

Answer 1

proteins released by cells that participate in the immune response

Question 2

How is cytokine expressed?

Answer 2

released extracellularly or expressed on surface of the cell

Question 3

How are cytokines recognized?

Answer 3

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

Question 4

what are the functions of cytokines in the immune response?

Answer 4

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

Question 5

how do cytokines act?

Answer 5

autocrine, paracrine, endocrine

Question 6

what is pleiotropy?

Answer 6

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

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

Question 7

what is redundancy?

Answer 7

cytokines have the same action

IL2, 4, 5 do proliferation

Question 8

what is synergy?

Answer 8

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

Question 9

what is antagonism?

Answer 9

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

Question 10

How is a cell fate decided?

Answer 10

cells integrate signals from many cytokines

Question 11

what are the phases of sepsis?

Answer 11

cytokine storm and immune suppression?

Question 12

what is the cytokine storm?

Answer 12

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

Question 13

what is the immune suppression in sepsis?

Answer 13

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

Question 14

cytokine treatments for sepsis

Answer 14

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

Question 15

what are the 7 cytokine families

Answer 15

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

Question 16

how are the cytokine families delineated

Answer 16

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

Question 17

Growth factor family receptor

Answer 17

tyrosine kinase domains

Question 18

growth factor family action

Answer 18

increased tyrosine phosphorylation signaling, immune cell differentiation

Question 19

TGF-B receptor

Answer 19

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

Question 20

TGF-B action

Answer 20

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

Question 21

IL-1 Family receptor

Answer 21

TIR domain, binding of MyD88

Question 22

IL-1 family action

Answer 22

MyD88 induces downstream signaling to activation NF-kB for inflammation

Question 23

What does IL-1Ra do?

Answer 23

inhibit IL-1

Question 24

TNF family receptor

Answer 24

TRAF and TRADD

Question 25

TNF family action

Answer 25

TRAF is inflammatory | TRADD does apoptosis

Question 26

What does TNF alpha and TNFR1 (receptor) do?

Answer 26

part of TNF family that can be inflammatory or do apoptosis

Question 27

IL-17 Family receptor

Answer 27

TLR and TNF

Question 28

IL-17 family action

Answer 28

dimerization and bind ACT1 which interacts with TRAF for inflammation

Question 29

Chemokine family receptor

Answer 29

7 transmembrane g protein coupled receptor

Question 30

chemokine family action

Answer 30

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

Question 31

what are the functions of chemokine receptors

Answer 31

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

Question 32

Classical cytokine family receptor

Answer 32

JAK/STAT, heterodimeric or trimeric

Question 33

Classical cytokine family action

Answer 33

activation of JAK kinases to phosphorylate STAT, lots of functions

Question 34

Type I Cytokine

Answer 34

Hemopoietin, conserved structural elements Conserved cysteines, conserved WSXWS, conserved y, conserved B, conserved gp130 differentiation, homeostasis, activation, suppression

Question 35

Type II Cytokine

Answer 35

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

Question 36

Three main classes of drugs targeting cytokine function

Answer 36

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

Question 37

How do recombinant cytokines work

Answer 37

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

Question 38

what is the exception to recombinant cytokines?

Answer 38

anakinra

Question 39

how does anakinra work?

Answer 39

IL-1Ra which inhibits IL-1

Question 40

what is the problem with recombinant cytokines

Answer 40

very powerful and substantial side effects

Question 41

how do antibodies targeting cytokines work?

Answer 41

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

Question 42

what is the problem is antibody cytokine drugs?

Answer 42

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

Question 43

how do small molecule inhibitors work?

Answer 43

inhibit JAK/STAT

Question 44

what are the problems with small molecule inhibitors?

Answer 44

increased infection, cancer, thrombocytopenia