Immunology 10 T Cell Polarization And Cytokine Signaling Part 2

Front 1

What does IL-7 do?

Back 1

It is important in B and T cell development.

Front 2

What does IL-15 do?

Back 2

It is important for NK cell development.

Front 3

What cytokines are important for NK cells?

Back 3

IL-15 for the development of NK cells. IL-22 and 23 for NK cell activity.

Front 4

Explain the role of negative feedback loops in T cell polarization.

Back 4

The products from one line of T cells inhibits the development of other types of T cells. For instance, IFN-gamma from Th1 cells inhibits the development of Th2 cells and other forms of CD4 T cells.

Front 5

What is IL-2 activity important for?

Back 5

The activation and medicinal suppression of the immune response

Front 6

What is the IL-2 receptor composed of?

Back 6

Alpha, beta, and gamma chains.

Front 7

Describe the IL-2 autocrine loop

Back 7

-Resting T cells express only a moderate-affinity IL-2 receptor (beta and gamma chains only)
-Activated T cells express a high-affinity IL-2 receptor (alpha, beta, gamma chains) and secrete IL-2
-Binding of IL-2 to its receptor signals the T cell to enter the cell cycle
-IL-2 induces T cell proliferation

Front 8

Explain TCR-mediates signal transduction

Back 8

The TCR, through a series of tyrosine kinases including ZAP70 activate a number of signaling cascades. Particular important is the activation of PLCgamma, which cleaves PIP2 into IP3 and DAG. IP3 releases intracellular calcium stores which activates specific proteins, such as calcineuron. At the end of these cascades are transcription factors. These transcription factors synergize to regulate the expression of cytokines.

Front 9

What is the end result of TCR-mediates signal transduction?

Back 9

Activation of transcription factors NFAT, NFkappaB, AP-1

Front 10

What does cyclosporin do?

Back 10

Block calcineurin and therefor the activation of NFAT and the subsequent expression of IL-2

Front 11

What does tacrolimus do?

Back 11

Block calcineurin and therefor the activation of NFAT and the subsequent expression of IL-2

Front 12

What is the relationship between calcineurin and NFAT?

Back 12

Calcineurin dephosphorylates the transcription factor NFAT, which resides in the cytoplasm. Once dephosphorylated it can translocate across the nucleus and along with the other transcription factors promote the expression of the IL-2 gene and the IL-2R alpha chain.

Front 13

What is the signature cytokine of Th1 cells?

Back 13

TH1 cells are good at activating macrophages through secretion of cytokines, particularly IFNgamma. These TH1 cells provide CD40 ligand, which is provides a second signal to help activate the macrophage. This interaction between T cells an d macrophages is particularly important for eliminating intracellular bacteria.

Front 14

What is the signature cytokine of Th2 cells?

Back 14

For TH2 cells the signature cytokine is IL-4. These Th2 cytokines activate B cells and there is a CD40 ligand which helps promote B cell survival during this process. These cytokines not only help promote B cell activation, but also secretion and isotype switching.

Front 15

What do IL-4, IL-5, and IL-6 do?

Back 15

These are the important Th2 effector cytokines.

Front 16

Describe Th17 cells

Back 16

IL-17 is a very potent inflammatory cytokine. Th17 cells are very important for extracellular bacteria. The largest respository of TH17 cells is in the GI tract. The GI tract accounts for most of the immune cells in the body.
-Secretes IL-21, IL-22, some IL-6 and prodigious IL-17A/F
-Th17 cells evolved to combath pathogens not covered by Th1 (intracellular) or Th2 (helminths) cells.
-IL-17 deficient mice are highly susceptible to EC pathogens
-IL-17 receptor is found on many cell types
-IL-17 activates granulocytes (innate immunity)
-IL-17 promotes cellular immunity by activating CD8 T-cells, NK cells, and macrophages
-IL-17 stimulates fibroblasts, endothelial cells, macrophages, and epithelial cells to produce multiple pro-inflammatory mediators (e.g. IL-1, IL-6, TNFalpha, NOS-2, metalloproteases, and chemokines).
-Th17/IL-21/IL-17 axis is important in the development of autoimmune disease.

Front 17

What occurs with too much Th1 activity?

Back 17

Type I diabetes

Front 18

What occurs with too much Th2 activity?

Back 18

Allergy
Asthma
Graft vs Host disease

Front 19

What occurs with too much Th17 activity?

Back 19

Destructive inflammation
Autoimmunity like MS and RA

Front 20

What cytokines are in the IL-12 family?

Back 20

IL-12, IL-23, IL-27, IL-35

Front 21

Describe the cytokines of the IL-12 family.

Back 21

Each ligand consists of two components: a classical 4 helix bundle cytokine and a cytoplasmic or shed receptor chain. The IL-12 and 23 receptors share one component. They share receptor chains so they have similar responses, but they also have different chains so they have different responses.

Front 22

What chemokine is associated with Th1?

Back 22

CXCL2

Front 23

What chemokine is associated with Th2?

Back 23

CCL11
CCL17

Front 24

What chemokine is associated with Th17?

Back 24

CCL2
CXCL10
CCL5

Front 25

What chemokine is associated with Tregs?

Back 25

CCL20

Front 26

How big are chemokines?

Back 26

Much smaller than cytokines. They are 10-12kD.

Front 27

What are chemokines useful for?

Back 27

Chemokines are important for leukocyte trafficking. They can also regulate the develop of specific organs or angiogenesis. They can regulate the survival of immune cells. They activate a number of well described signaling pathways. Both the receptor and these signaling pathways turn out to be important drug targets.

Front 28

Which cells have CCR7?

Back 28

Mature DC
Naive T cells

Front 29

What are the two functional classes of chemokines?

Back 29

Homeostatic chemokines
Inflammatory chemokines

Front 30

Describe homeostatic chemokines.

Back 30

They are involved in the development of immune tissues
-These chemokines direct the basal or homeostatic distribution of leukocytes to immune tissues
-Homeostatic chemokines include: S1P, CCL19, CCL21, CXCL12. CXCL13

The homeostatic receptors and chemokines make sure that as the organism is developing in an uninfected state those leukocytes go where they are supposed to go.

Front 31

Describe inflammatory chemokines.

Back 31

They are involved in acute and chronic inflammation.
-Danger signals, many chemokines are involved in directing leukocyte traffic during infection and inflammation (chronic and acute)
-Inflammatory chemokines include: CCL2, CCL5, CCL11, CXCK8, CXCL9, CXCL10
-There are some chemokines with dual activity

Front 32

What does IL-8/CXCL8 do?

Back 32

It is a potent inflammatory chemoattractant for PMNs

Front 33

What chemokine receptors serve as co-receptors for HIV?

Back 33

CXCR4 and CCR5

Front 34

Describe the structure of chemokine receptors

Back 34

They are G-protein coupled receptors

Front 35

What are some of the families of non-classical chemokines?

Back 35

Lipid-based
Peptide-based