Exam 3: Cytokines Flashcards

1
Q

What are cytokines?

A

Small, soluble proteins used by immune cells for communication

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2
Q

4 different cytokine properties

A
  1. Pleiotropic
  2. Redundant
  3. Synergistic
  4. Antagonistic
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3
Q

Signaling mech for many cytokines

A

JAK/STAT system

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4
Q

Role of cytokines and chemokines

A

fine-tuning of an immune response as it progresses

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5
Q

Functions of Cytokines

A
Stimulation (IL-2)
Inhibition (TGF-β)
Differentiation (IL-12, IL4, Il-23)
Cell death (TNF)
Chemoattract
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6
Q

3 modes of action

A
Autocrine --> Act on cell that produces them like IL-2 (respond to its own signal)
Paracrine--> Act on nearby cell (class switching, T cells activating macrophages)
Endocrine--> Act on distant cells via circulation (IL-1 acts on brain)
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7
Q

Properties of cytokines: Pleiotropy

A

1 cytokine has multiple effects on multiple cell types
Ex: IL-4 induces activation, proliferation, differentiation of B cells; proliferation of T cells; proliferation of Mast cells

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8
Q

Properties of cytokines: Redundancy

A

> 1 cytokine can have same effect

Ex: IL-2, IL-4, IL-5 induce proliferation of B cells

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9
Q

Properties of cytokines: Synergy

A
2 cytokines acting together have different or amplified effect than by themselves
Ex: IL-4 + IL-5 dramatically increase IgE class switching when IL-5 does not have this affect alone and IL-4 exhibit lesser class switching
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10
Q

Properties of cytokines: Antagonism

A

cytokines interfere with another’s effect

Ex: IL-4 induces TH2 but inhibits TH1 and TH17; IFN-γ induces TH1 but inhibits TH2 and TH17

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11
Q

What cytokine(s) released by activated macrophages induce (s) change in vascular endothelium (vasodilation) that allow more leakiness of leukocytes and allow fluid to enter lymph system? (Local effect)

A

IL-1, TNF-α

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12
Q

Local effects rely on ___ levels of cytokines

A

Higher

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13
Q

Systemic effects result from TNF-α entering ____

A

bloodstream

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14
Q

Septic shock induces by __

A

systemic infection

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15
Q

Systemic infection (Too much immune response)

A

edema causes decreased blood volume leading to collapse of vessels, coagulation leads to multiple organ failure

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16
Q

What cytokines do virally infected cells secrete?

A

IFN-α; IFN-β
These induce resistance to viral replication replication in all cells by increasing MHC I expression and antigen presentation in all cells and activating NK cells to kill these infected cells

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17
Q

TH1 or TH2?

IL-2

A

TH1

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18
Q

TH1 or TH2?

IFN-γ

A

TH1

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19
Q

TH1 or TH2?

TNF-β

A

TH1

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20
Q

TH1 or TH2?

GM-CSF

A

TH1

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21
Q

TH1 or TH2?

IL-3

A

TH1 and TTH2

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22
Q

TH1 or TH2?

IL-4

A

TH2

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23
Q

TH1 or TH2?

IL-5

A

TH2

24
Q

TH1 or TH2?

Il-10

A

TH2

25
Q

TH1 or TH2?

IL-13

A

TH2

26
Q

TH1 or TH2?

Help IgE production

A

IgG via IL-4

27
Q

TH1 or TH2?

Help IgG2a production

A

TH1 mostly; also TH2

28
Q

TH1 or TH2?

Eosinophil and Mast Cell production

A

TH2

29
Q

TH1 or TH2?

Delayed type hypersensitivity

A

TH1

30
Q

TH1 or TH2?

CTL activation

A

TH1

31
Q

What are the 5 cytokine receptor families?

A
  1. Class I (hematopoietin)
  2. Class 2 (interferon)
  3. TNF
  4. Immunoglobulin superfamily
  5. Cytokine
32
Q

Which receptor families are characterized by conserved cysteines in extracellular domain?

A

Class 1 (hemotopoein), Class II (interferon), TNF

33
Q

Match ligand to receptor family: IL-4, IL-2

A

Class 1

34
Q

Match ligand to family: IL-5

A

Class 1

35
Q

Match ligand to family: IL-12

A

Class 1

36
Q

Match ligand to family: IL-21

A

Class 1

37
Q

Match ligand to family: IL-23

A

Class 1

38
Q

Match ligand to family: IFN- alpha, beta, gamma

A

Class 2

39
Q

Match ligand to family: TNF- alpha, beta

A

TNF

40
Q

Match ligand to family -1

A

Ig superfamily

41
Q

Which families utilize JAK/STAT pathway

A

Class 1, Class 2, TNF

42
Q

CD27L, CD30L, and CD40L are membrane bound____

A

costimu molecules

43
Q

Structure of chemokine receptors

A

7 transmembrane receptors using trimeric G-proteins as signaling

44
Q

3 subfamilies

A
  1. GM-CSF (common beta subunit)
  2. IL-6 (common gp130 subunit)
  3. IL-2 (common gamma subunit)
    based on similar signaling pathways
45
Q

IL-2 Receptor (IL-2R) expression

A

More subunits lead to higher affinity
just alpha: low affinity (10^-8 M)
gamma and beta subunit: intermediate affinity (10^-9 M)
alpha, gamma, and beta: high affinity (10^-11 M)
need less cytokine concentration for higher affinity receptor

46
Q

IL-2R (low and high affinity)

A

Activated CD4 and CD8 T cells and activated B cells

47
Q

Naive T cells and NK cells express which IL-2R subunits

A

gamma and beta

48
Q

Which subunit modulates IL-2R

A

alpha

49
Q

**Describe the JAK/STAT pathway? **

A

cytokine receptors interact with inactive JAK (Janus kinase); cytokine binding to receptor induces receptor subunits to dimerize and activates JAK and the receptor chains are phosphorylated (specifically tyrosines); Phosphorylated tyrosines bind to SH2 containing protein STAT (STAT is phosphorylated); STAT normally inactive in cytosol, when SH2 binds to phosphorylated tyrosine on receptor, STAT becomes target and dimerize (homo and hetero): dimerized STAT move into nucleus and act as transcription factors
ESSENTIALLY JAKS BIND TO RECEPTOR SUBUNITS TO PHOSPHORYLATE DIFFERENT STATS

50
Q

IL-2 receptor interacts with JAK_ and JAK_ and activates STAT_

A

JAK1; JAK3; STAT5

51
Q

IL-4 receptor interacts with JAK_ and JAK_ and activates STAT_

A

JAK1; JAK3; STAT6

52
Q

IL-12 receptor interacts with JAK_ and ___ and activates STAT_

A

JAK2; Tyk-2; STAT4

53
Q

IFN-gamma receptor interacts with JAK_ and JAK_ and activates STAT_

A

JAKW1; JAK2; STAT1

54
Q

Even with limited # JAKS, we can activate ___

A

different subsets of STATs based on different cytokines

55
Q

Chemokine receptors structure

A

7 transmembrane domain receptors signal by coupling with trimeric GTP-binding proteins–> Chemotaxis