Block 1 Lecture 5 -- Cytokines

Question 1

When are Type I IFN’s released?

Answer 1

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

Question 2

What are the effects of Type I IFNs?

Answer 2

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

Question 3

Which cells secrete TNF-alpha?

Answer 3

monocytes

Question 4

What are the effects of TNF-alpha?

Answer 4

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

Question 5

Where is IL-21 released from?

Answer 5

CD4+ T cells

Question 6

Effects of IL-21?

Answer 6

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

Question 7

What is GM-CSF?

Answer 7

granulocyte-macrophage colony-stimulating factor

Question 8

Effects of GM-CSF

Answer 8

granulocyte survival and activation

DC maturation

Question 9

Effects of M-CSF?

Answer 9

survival and activation of macrophages

mobilization of myeloid cells

Question 10

What is M-CSF?

Answer 10

macrophage colony stimulating factor

Question 11

What cytokines are inhibitory?

Answer 11

TGF-beta, IL-10

Question 12

Which co-receptors does HIV recognize?

Answer 12

CCR5, CXCR4 (chemokine receptors)

Question 13

What chemokines are expressed in the T-cell zone?

Answer 13

CCL19, CCL21

Question 14

What chemokines are expressed in the B-cell zone?

Answer 14

CXCL13

Question 15

What receptor binds CXCL13

Answer 15

X5

Question 16

What receptor binds CCL19, CCL21?

Answer 16

R7

Question 17

What are chemokines?

Answer 17

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

Question 18

What are the families of chemokines?

Answer 18

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

Question 19

Function of beta family chemokines

Answer 19

recruit monocytes and lymphocytes

Question 20

Function of alpha family chemokines

Answer 20

recruit neutrophils and lymphocytes

Question 21

Describe CCL4

Answer 21

binds to CCR5

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

Question 22

Describe CXCL8/IL-8

Answer 22

binds CXCR1/1

– recruits neutrophils

Question 23

Describe CXCL12

Answer 23

binds CXCR4

• • recruits leukocytes
• • HIV coreceptor

Question 24

How are cytokines classified?

Answer 24

by receptor class

– further by AA differences which determine cytokine specificity

Question 25

What are the cytokine receptors?

Answer 25

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

Question 26

Describe structure of cytokine receptors:

Answer 26

extracellular binding domain | intracellular signaling domain

Question 27

What are the 3 phases of signal transduction?

Answer 27

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

Question 28

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

Answer 28

receptor TK

Question 29

Describe JAK-STAT signaling

Answer 29

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

Question 30

What is the role of JAK-STAT signaling?

Answer 30

cell activation and over-activation | -- target for autoimmune disorders, cancers

Question 31

Describe TNF-receptor signaling.

Answer 31

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

Question 32

What kind of cytokine deficiencies cause clinical problems?

Answer 32

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

Question 33

How is IL-12r deficiency treated?

Answer 33

IgG and Abx

Question 34

What causes cytokine overexpression?

Answer 34

infection, autoimmunity, some therapies

Question 35

How is cytokine storm treated?

Answer 35

steroids abx cytokine inhibitors