Lecture 15: Cytokine Signals Flashcards

1
Q

Cytokine signaling function

A

-macrogphages to induce cell migration
-B cell development for Igs
-blood differentiation
-T cell activation
-cell proliferation
-wound healing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Expression of cytokines and receptors

A

-highly regulated
-control pro and anti inflammatory response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Macrophage release of chemokines induces

A

neutrophil migration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Neutrophil migration

A

-innate immunity
-infection activates macrophage to release chemokines that recruit cells
-IL-1B, TNF-a, IL-6, CXCL8, IL-12
-all lead to inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Cytokines released from macrophages

A

-IL-1B
-TNF-a
-IL-6
-CXCL8
-IL-12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

IL-1B and TNF-a

A

-increase blood vessel permeability
-allow cells and fluid to enter infected tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

IL-6

A

-induces fat and muscle metabolism
-raise temp in tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

CXCL8

A

-recruits neutrophils from blood and guides them to tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

IL-12

A

-recruits/activates NK cells that secrete cytokines that strengthen macrophage response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Neutrophil in absence of infection

A

-circulate in blood
-rolling adhesion on selectin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

selectin

A

-glycoproteins that weakly bind to sialyl-Lewis X carbs on neutrophills in blood stream
=rolling adhesion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Neutrophil recruitment

A
  1. Rolling adhesion
  2. Tight binding
  3. Diapedesis
  4. Migration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

ICAM-1

A

-cell-adhesion molecule
-induced by TNFa
-binds LFA-1 on neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Tight binding

A

-ICAM-1 initiates binding to LFA-1 integrin on neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Diapedesis

A

-after binding LFA-1, neutrophils can cross endothelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Migration

A

-CXCL8 secreted by macrophages directs neutrophils across endothelium and to the tissue
-moves along gradient of CXCL8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

monocytes (premacrophage)

A

-similar process to neutrophils
-recruited by CCL2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

CXCL8 is a chemokine because

A

it promotes movement of various immune cells in a certain direction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Cytokine Receptor families (excluding chemokine/GPCR)

A

-TNF
-Type I and II cytokine receptors
-IL-1
-IL-17

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

TNF receptor family

A

-trimeric cysteine
-TNF-a
-fibronectin domain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Type I and II families

A

-both have JAK/STAT pathways
-IL-6
-cysteine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

IL-1 receptor family

A

Ig like

23
Q

IL-17 family

A

-IL-17 ligand

24
Q

fibronectin domain

A
25
Q

TNFa

A

-membrane anchored or soluble forms
-released by lymphocytes and monocytes during infection
-target TNFR1 and 2
-fever, apoptosis, inflammation

26
Q

TNFa release

A

-from lymphocytes and monocytes
-along with IL-1, IL-6, interfeon y

27
Q

TNFa receptors

A

-cys rich domains
-TNFR1 and TNFR2

28
Q

TNFR1

A

-constitutively expressed on most cell types
-PRO inflammatory
-apoptotic

29
Q

TNFR2

A

-restricted to endothelial, epithelial, some immune cells
-ANTI inflammatory
-cell proliferation

30
Q

TNFa signaling pathway

A

-TNFa binding leads to receptor oligomerization
-generates active complex of multiple proteins
-activates NF-kB or MAPK pathway
-effects often conflict

31
Q

TNFa dysregulation

A

-alzheimers, depression, IBD

32
Q

Tasonermin

A

-TNFa itself
-immunostimulant to treat some cancers

33
Q

Etanercept

A

-treat rheumatoid arthritis and psoriarisis
-prevent ligand binding to receptor
-fusion protein made by recombinant DNA
-extracellular TNFR2 fused to Fc region of IgG1 antibody

34
Q

Type I receptors

A

-common chain for different subfamilies = redundancy
-IL-15 and IL-4 y chain
-GM-CSF and IL-5 B chain
-IL-6 and IL-11 gp130 chain

35
Q

common chain type I

A

-cytokine binds to a subunit
-complex associates with B subunit (cross-react)
-signal transduced through B subunit (redundancy)

36
Q

IL-6 and receptor common gp130 and signaling pathways

A
37
Q

IL-6

A

-PRO inflammatory
-secreted by T cells
-important for differentiation of T and B cells

38
Q

IL-6 receptor signaling

A

-forms heterohexameric complex
: (IL-6, gp130, IL-6Ra) x2
-common gp130 chain response activates PI3K, JAK, MAPK
-stimulates accute phase protein synthesis, survival, production of neutrophils, regulates inflammation

39
Q

Heterohexameric complex

A

-association of IL-6 with IL-6Ra
-then with gp130 = trimer
-trimer dimerizes

40
Q

JAK/STAT pathway

A

-type I and II receptors
1. JAK kinase w/ receptor
2. cytokine binding dimerizes receptor = pair of JAK kinases
3. JAK activated, phosphorylzes receptor
4. STAT docks and is phosphorylated
5. pSTAT dissociates and pSTAT dimerizes
6. pSTAT dimer goes to nucleus and mediates transcription of target gene

41
Q

Redundancy from

A

-common chain
-all stimulate B cell proliferation
-all trigger JAK/STAT pathway

42
Q

IL-6 dysregulation

A

-rheumatoid arthritis, sclerosis, lupus, prostate cancer, myeloma

43
Q

IL-6 in cancer

A

-chronic inflammation
-regulation of tumor microenvironments and metastisis

44
Q

Enterovirus 71

A

-contagious
-mild illness
-hand/foot/mouth disease
-LEADS to ENCEPHALITIS which IL-6 contributes to

45
Q

Drugs against IL-6

A

-siltuximab
-tocilizumab and sailumab

46
Q

siltuximab

A

-antibody against IL-6
-binds ligand so it cannot get to receptor
-treats castleman disease

47
Q

tocilizumab and sarilumab

A

-Igs against soluble and membrane bound IL-6R
-treat rheumatoid arthritis
-bind to receptor

48
Q

IL-17

A

-homodimer and heterodimer of IL-17 A and F
-secreted by T cells
-thought to be heterotrimer with C

49
Q

IL-17 targets

A

-macrophages
-T cells
-endothelial cells
-fibroblasts

50
Q

IL-17 signaling pathway

A

-ACT 1 association with receptor and kinases
-increase expression of PRO inflammatory cytokines

51
Q

IL-17 effects

A

-PRO inflammatory
-good vs bacteria and fungus

52
Q

IL-17 overexpression

A

-asthma
-COPD
-dampens anti-tumor immunity

53
Q

Secukinumab

A

Ig against IL-17A
-treat psoriaisis