Term
| Two mechanisms of tolerance and where they are established? |
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Definition
Central - thymus
Peripheral - lymph nodes |
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Term
| Three mechanisms of peripheral tolerence |
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Definition
1) Regulatory T-cells
2) Myeoloid derived suppressor cells: myeoloid cells become immunoregulatory cells when exposed to inflammatory cytokines and activated T-cells to prevent further stimulation
3) Inappropriate or insufficient co-stimulation of a T cell int he presence of its antigen -anergy |
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Term
Where are regulatory T-cells created?
What type of T-cell become Tregs there? |
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Definition
Hassal's corpuscles
- Cells tha thave intermediate affinity to self-antigens and are not eliminated by negative selection mature in to FoxP3+ Tregs |
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Term
| In central tolerence, what prevents T-cells from later destorying peripheral tissue? |
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Definition
- expression of AIRE by thymic stromal (epithelial) cells.
AIRE codes for peripheral tissue antigen and these are presented to developing thymocytes |
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Term
| What does a mutation in AIRE cause? |
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Definition
| Autoimmune polyendocrine syndrome 1 - inability of peripheral tissue antigen to be presented to developing T-cells in thymus. |
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Term
| Two mechanisms that are the cellular basis for peripheral tolerance |
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Definition
1) Dominant supression by professional regulatory cell
2) cell intrinsic inactivation: change of the state of T-cells |
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Term
What cell type is responsible for dominant suppression (be specific) and where are they generated?
What do they express?
What stimulates them?
What do they produce? |
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Definition
- nTregs - naturally occuring Tregs that grow up in the thymus
- express FoxP3
- stimulated by Il 10 and TGF-β
- produce adenosine to suppress other lymphocytes
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Term
| What are nTreg's diversity mostly limited to? |
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Definition
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Term
What is the growth factor that is essential for nTreg maintenance?
What two growth factors enhance Treg functions? |
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Definition
nTreg maintenence: IL-2
IL10, TGF-β |
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Term
what type of Treg does not express FoxP3?
What do they produce?
What growth factors induce their development? |
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Definition
TR1 cells
- produce IL10, immunosuppressive cytokine
-TGF-β and IL-27 or just IL10 |
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Term
| What is required for nTreg's to suppress T cells? |
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Definition
| Direct cell to cell contact |
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Term
What induces iTregs?
What inhibits them?
What vitamin acts as a cofactor to induce iTregs? |
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Definition
induced by : antigen presenting cells that are present in the mucosal environment, like the intestine.
Inhibited by: IL-6
- vitamin A induces |
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Term
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Definition
| The state of T-cells that are unresponsive to antigen |
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Term
| Difference between nTregs and iTregs? |
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Definition
| - iTregs develop outside of the thymus |
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Term
| Other than IL2 and TGF-β, what else can promote the development of iTregs? |
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Definition
Infectious agents
food/nutirtion: vitamin A
Aryl Hydrocarbon receptor ligands (dioxene) are potent inducers of FOXP3 expressing Tregs (nTregs and iTregs) |
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Term
How T cells become anergic in vivo?
Why? |
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Definition
- when antigens are presetned by othe rtypes of cells besides APC's.
- stimulation requires B7 to interact with T-cell CD28, but only APC's have B7. |
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Term
CTLA-4:
What produces it?
What does it do? |
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Definition
CTLA4 is produced by Tregs
- competes with CD28 for B7 on APC and ultimately wins
- CTLA4 also recruits signaling molecules that suppress TCR signaling, further blocking antigen activation |
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