Block 1 Lecture 5 -- Cytokines Flashcards

1
Q

When are Type I IFN’s released?

A

in response to cellular infection (fever, muscle, flu-like symptoms)

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2
Q

What are the effects of Type I IFNs?

A

1) DC: activation, migration, IL-12 production
- - T/NK activation, cytotoxicity
2) macrophages: antimicrobial genes, death sensitization
3) T/NK: stimulates IFN-y production
- - activated macrophages, Ts, Bs
4) epithelium: inhibits bacterial invasion
5) inflammatory cells: enhanced septic shock

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3
Q

Which cells secrete TNF-alpha?

A

monocytes

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4
Q

What are the effects of TNF-alpha?

A

1) macrophages: IL-6, IL-1, adhesion
2) neutrophils: activation, ROS
3) endothelium: activation
4) DC: inhibition
5) T: IL-6, IL-10, TGF-beta, acute phase proteins
- - immunosuppression

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5
Q

Where is IL-21 released from?

A

CD4+ T cells

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6
Q

Effects of IL-21?

A

1) macrophages: activation, IL-8
- - neutrophil recruitment
2) DCs: increased Ag uptake, decreased presentation
3) CTL/NK: proliferation, TNF-alpha
- - inflammation
4) B: isotype switching, Ab production

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7
Q

What is GM-CSF?

A

granulocyte-macrophage colony-stimulating factor

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8
Q

Effects of GM-CSF

A

granulocyte survival and activation

DC maturation

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9
Q

Effects of M-CSF?

A

survival and activation of macrophages

mobilization of myeloid cells

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10
Q

What is M-CSF?

A

macrophage colony stimulating factor

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11
Q

What cytokines are inhibitory?

A

TGF-beta, IL-10

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12
Q

Which co-receptors does HIV recognize?

A

CCR5, CXCR4 (chemokine receptors)

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13
Q

What chemokines are expressed in the T-cell zone?

A

CCL19, CCL21

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14
Q

What chemokines are expressed in the B-cell zone?

A

CXCL13

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15
Q

What receptor binds CXCL13

A

X5

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16
Q

What receptor binds CCL19, CCL21?

A

R7

17
Q

What are chemokines?

A

soluble proteins (8-10 kDa) secreted by all immune cells according to microbe, cytokines, or inflammatory response

18
Q

What are the families of chemokines?

A

1) CC (beta)
2) CXC (alpha)
3) C, CX3C, others

19
Q

Function of beta family chemokines

A

recruit monocytes and lymphocytes

20
Q

Function of alpha family chemokines

A

recruit neutrophils and lymphocytes

21
Q

Describe CCL4

A

binds to CCR5

    • recruits T, DC, monocyte, NK
    • HIV coreceptor
22
Q

Describe CXCL8/IL-8

A

binds CXCR1/1

– recruits neutrophils

23
Q

Describe CXCL12

A

binds CXCR4

    • recruits leukocytes
    • HIV coreceptor
24
Q

How are cytokines classified?

A

by receptor class

– further by AA differences which determine cytokine specificity

25
Q

What are the cytokine receptors?

A

1) Type 1
2) Type II
3) TNF-receptor
4) IL-1 receptor
5) GPCRs

26
Q

Describe structure of cytokine receptors:

A

extracellular binding domain

intracellular signaling domain

27
Q

What are the 3 phases of signal transduction?

A

1) ligand binding
2) cytosolic phase
- - formation of modified TF
3) nucelar phase
- - gene transcription

28
Q

With which kind of receptor is the JAK-STAT pathway associated?

A

receptor TK

29
Q

Describe JAK-STAT signaling

A

1) binding-mediated receptor dimerization
2) JAK-mediated receptor phosphorylation
3) STATs recruited, phosphorylated
4) 2x STAT translocate and become TFs

30
Q

What is the role of JAK-STAT signaling?

A

cell activation and over-activation

– target for autoimmune disorders, cancers

31
Q

Describe TNF-receptor signaling.

A

1) TNF-binding
2) adaptor protein TRADD binds intracellularly
3) signaling intermediates associate
4) generation of active transcription factors

32
Q

What kind of cytokine deficiencies cause clinical problems?

A

1) Fe-deficiency anemia = decreased IL-6
- - infection
2) IL-12r deficiency
- - T/NK under-activation

33
Q

How is IL-12r deficiency treated?

A

IgG and Abx

34
Q

What causes cytokine overexpression?

A

infection, autoimmunity, some therapies

35
Q

How is cytokine storm treated?

A

steroids
abx
cytokine inhibitors