Exam 2: Immune System Regulation Flashcards
What are the three kinds of T cells?
T killer cells –> kills other cells
T helper cells –> helps other cells
T regulatory cells–> restrains the immune system
In presence of what cytokine may a T cell become a Tr (T regulatory) cell?
presence of TGFbeta
What do activated T Helper cells secrete? What effect does this have on the immune system?
secrete TNF and IFN-gama
activate immune system
What do activated regulatory T cells secrete? What effect does this have on the immune system?
secrete TGFbeta and iL-10
restrain immune system
What are two cytokines Regulatory T cell secrete?
TGFbeta (Transforming Growth Factor Beta)
IL-10
What does the cytokine TGFbeta secreted by Tr cells do? (3)
- binds to receptors on T cells
- reduces proliferation
- reduces CTL killing
What does the cytokine IL-10 secreted by Tr cells do? (3)
- binds to receptors on T cells
- blocks co-stimulatory signals (Cd28) –> therefore more difficult to activate
- reduces proliferation
What two things are usually associated with inducing regulatory T cells?
intestines and allergies
How do intestines induce regulatory T cells?
- 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
How are Regulatory T cells involved with allergies?
control mast cell degranulation and prevent allergies
What else are Regulatory T cells often called?
iTreg (inducible) or more recently pTreg cells (peripheral)
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)?
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
Compare the affinity of CD28 and CTLA-4 and binding to B7.
What does this result in?
CTLA-4 binds to B7 with an affinity 1000s of times higher than CD28
–> out competes CD28 resulting in slow down
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?
CD28
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?
CTLA-4
When B7 binds to naive T cell’s CD28, what occurs?
co-stimulation and ACTIVATION
When CTLA-4 binds the B7 co-stimulatory molecules, what occurs?
blocks co-stimulation and blocks activation
What else can be expressed on the T cell besides the CTLA-4, that will turn down the response?
PD-1 on the T cell will engage PD-1L expressed on APCs and target cells and turn down the response
What is PD-1 and how is this associated with regulation of T cells?
= 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
What can any cell expressing PD-1 do?
could be down regulated by engaging PD1-L
PD-1 is on T cell
What can any cell expressing PD1-L do?
can turn “down” immune response
PD1-L is on target cell/APC
Once a T cell is activated, what happens to its longevity?
it is greatly reduced
– AICD (Activation-Induced Cell Death)
just another way to control T cells
What is AICD?
= Activation-Induced Cell Death
- another way to control T cells
- involves Fas proteins
What does AICD involve?
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”)
How does AICD work with experienced T cells?
Fas/FasL on same cell can engage (suicide)
or
Fas on T cell engages FasL on other T cells causing apoptosis (“homocide”)
Summary: What are the three Negative Regulators for T cells?
- CTLA-4 (competes and binds B7)
- Fas protein
- PD-1 (engaes PD-1L expressed on APCs and target cells
What are the lifespans of these immune cells/molecules?
- Neutrophils
- Natural KIller cells
- Macrophages
- Dendritic cells
- Plasma B cells
- Antibodies
- die after few days
- 1-2 wks
- months
- live for a week after reaching a lymph node
- die after ~5 days of making 2000 Abs/sec
- longest lived (IgG) has a half life of 3 wks
