Exam 2: Immune System Regulation

Question 1

What are the three kinds of T cells?

Answer 1

T killer cells –> kills other cells

T helper cells –> helps other cells

T regulatory cells–> restrains the immune system

Question 2

In presence of what cytokine may a T cell become a Tr (T regulatory) cell?

Answer 2

presence of TGFbeta

Question 3

What do activated T Helper cells secrete? What effect does this have on the immune system?

Answer 3

secrete TNF and IFN-gama

activate immune system

Question 4

What do activated regulatory T cells secrete? What effect does this have on the immune system?

Answer 4

secrete TGFbeta and iL-10

restrain immune system

Question 5

What are two cytokines Regulatory T cell secrete?

Answer 5

TGFbeta (Transforming Growth Factor Beta)

IL-10

Question 6

What does the cytokine TGFbeta secreted by Tr cells do? (3)

Answer 6

• binds to receptors on T cells
• reduces proliferation
• reduces CTL killing

Question 7

What does the cytokine IL-10 secreted by Tr cells do? (3)

Answer 7

• binds to receptors on T cells
• blocks co-stimulatory signals (Cd28) –> therefore more difficult to activate
• reduces proliferation

Question 8

What two things are usually associated with inducing regulatory T cells?

Answer 8

intestines and allergies

Question 9

How do intestines induce regulatory T cells?

Answer 9

• epithelial cells of intestine produce TGFbeta–> causing T cells in Peyer’s Patches to become Tr cells –> Tr cells release cytokines to encourage a calmer mucosal immune system

Question 10

How are Regulatory T cells involved with allergies?

Answer 10

control mast cell degranulation and prevent allergies

Question 11

What else are Regulatory T cells often called?

Answer 11

iTreg (inducible) or more recently pTreg cells (peripheral)

Question 12

Describe the way of deactivating T cells and the involvement of CD28 and CTLA-4. What do virgin T cells express more of? What baout experienced T cells (older)?

Answer 12

virgin T cells express many–> CD28 receptors for co-stimulate and activated APCs make lots of B7 that binds to CD28 = activating T cell

experienced T cells –> make more CTLA-4, which binds to B7 also and therefore blocks CD28 and reducing response

Question 13

Compare the affinity of CD28 and CTLA-4 and binding to B7.

What does this result in?

Answer 13

CTLA-4 binds to B7 with an affinity 1000s of times higher than CD28

–> out competes CD28 resulting in slow down

Question 14

What is a receptor molecule on the T cell that when activated amplifies the signal and lowers the number of TCR crosslinks neeeded for activation?

Answer 14

CD28

Question 15

What is a receptor molecule on the very experienced T cells what when brought to the surface is competes for B7, making co-stimulation and activation more difficult?

Answer 15

CTLA-4

Question 16

When B7 binds to naive T cell’s CD28, what occurs?

Answer 16

co-stimulation and ACTIVATION

Question 17

When CTLA-4 binds the B7 co-stimulatory molecules, what occurs?

Answer 17

blocks co-stimulation and blocks activation

Question 18

What else can be expressed on the T cell besides the CTLA-4, that will turn down the response?

Answer 18

PD-1 on the T cell will engage PD-1L expressed on APCs and target cells and turn down the response

Question 19

What is PD-1 and how is this associated with regulation of T cells?

Answer 19

= Programmed Death 1 receptor
- is expressed on activated T cells (and other cells)

PD1-L is expressed on other WBCs and inflamed tissue

engagement of PD-1 and PD1-L = slows proliferation and may induce apoptosis

Question 20

What can any cell expressing PD-1 do?

Answer 20

could be down regulated by engaging PD1-L

PD-1 is on T cell

Question 21

What can any cell expressing PD1-L do?

Answer 21

can turn “down” immune response

PD1-L is on target cell/APC

Question 22

Once a T cell is activated, what happens to its longevity?

Answer 22

it is greatly reduced
– AICD (Activation-Induced Cell Death)

just another way to control T cells

Question 23

What is AICD?

Answer 23

= Activation-Induced Cell Death

• another way to control T cells
• involves Fas proteins

Question 24

What does AICD involve?

Answer 24

Fas receptor protein is a death receptor on the surface of cells

Virgin T cells–> Fas proteins are insensitive to ligation

Experienced T cells–> Fas proteins are sensitive

—Fas/FasL on same cell can engage (suicide) or Fas on T cell engages FasL on other T cells causing apoptosis (“homocide”)

Question 25

How does AICD work with experienced T cells?

Answer 25

Fas/FasL on same cell can engage (suicide)
or
Fas on T cell engages FasL on other T cells causing apoptosis (“homocide”)

Question 26

Summary: What are the three Negative Regulators for T cells?

Answer 26

1. CTLA-4 (competes and binds B7)
2. Fas protein
3. PD-1 (engaes PD-1L expressed on APCs and target cells

Question 27

What are the lifespans of these immune cells/molecules?

1. Neutrophils
2. Natural KIller cells
3. Macrophages
4. Dendritic cells
5. Plasma B cells
6. Antibodies

Answer 27

1. die after few days
2. 1-2 wks
3. months
4. live for a week after reaching a lymph node
5. die after ~5 days of making 2000 Abs/sec
6. longest lived (IgG) has a half life of 3 wks