Quiz 7 Flashcards
What is an autoimmune reaction?
immune response to self antigen
What is central tolerance?
T cell development/selection (removing auto reactive T cells)
What is peripheral tolerance?
Tregs and suppression/anergy of self-reactive T cells
What are the polarizing cytokines for Tregs?
IL-2 and TGF-B
What are the effector cytokines for Tregs?
IL-10 and TGF-B
What are the 4 outcomes of Treg–MHC interaction?
- IL-10 expression
- CTLA-4 expression
- IL-2R upregulation
- linked expression
When Tregs and MHC interact, what is the purpose of IL-10 expression?
inhibits MHC on APCs
inhibits B7/CD28
inhibits TNF-a and IL-6
When Tregs and MHC interact, what is the purpose of CTLA-4 expression?
binds with B7 on APC to induce anergy
When Tregs and MHC interact, what is the purpose of IL-2R (CD25) being up regulated?
binds IL-2 = outcompetes for T cell activation
When Tregs and MHC interact, what is the purpose of linked expression?
Treg can bind and inhibit 2 T effectors bound to an APC
What is the steps of central tolerance for T cells?
- HSC
- blood
- double negative
- thymus cortex (positive selection)
- double positive
- thymus medulla (negative selection)
- single positive
- blood
Where does positive selection happen?
thymus cortex
Where does negative selection happen?
thymus medulla
What is positive selection?
T cell is functional and equipped to make a response against foreign antigens
What is negative selection?
deletes T cells with high affinity for self-peptides via apoptosis, thus ensuring self tolerance
What presents to double positive T cells in positive selection?
cTEC/DC/macrophage
What presents to single positive T cells in negative selection?
AIRE + mTECs
What are the three fates of double positive T cell in positive selection?
- intermediate affinity = single positive
- high affinity for MHC = apoptosis
- no recognition = death by neglect
In negative selection what affinity do you want the TCR to have?
intermediate affinity
How does AIRE+ mTEC present self antigen?
opens DNA region
Transport of single positive T cells out of thymus is mediated by ________
S1P and S1PR (on T cell)
How does S1P mediate SP T cell transport out of the thymus?
T cell follows the concentration gradient
(S1P is high in the blood and low in the thymus)
What does the drug FTY720 prevent autoimmunity?
binds to S1PR on T cells to prevent them from leaving the thymus (prevents auto reactive T cells from leaving the thymus)
Peripheral tolerance follows ___________
central tolerance
What is the purpose of peripheral tolerance?
sometimes auto reactive T cells make it through the selection process and into the blood and they need to be eliminated
What is the disorder APECED?
mutation in AIRE causing there to be not presentation of self during negative selection
Why are people with APECED prone to yeast infections?
IFN-a and IL-17 activity id blocked which is important for Th17 functions of protection against fungi
What is the ELISA test for?
tests for autoantibodies in APECED patients (typically IgG)
What are 3 trademarks for APECED?
- reduced expression of self-antigen
- reduced IFN-a (due to anti-cytokine Ab)
- reduced IL-17 (due to anti-cytokine Ab)
APECED patients also have loss of B cell tolerance, how does this happen?
B cells depend on T cells for SHM
auto-reactive T cells make conjugate pair with B cells = auto-reactive Ab
What T cells mediate psoriasis?
Th17
Th23
Th1
What are 3 alterations of skin in psoriasis?
- redness
- skin thickening
- white scales
What causes the redness in psoriasis?
vasodilation and inflamed endothelial cells
What causes the skin thickening in psoriasis?
hyper-proliferation of keratinocytes
What causes the white scalees in psoriasis?
parakeratosis (top layer of keratinocytes won’t loose nucleus and die)
What is parakeratosis?
top layer of keratinocytes won’t loose nucleus and die
Where does all of the skin affects of psoriasis occur?
stratum corneum
Because of the dysfunction of skin in psoriasis what 3 things occur making it a skin barrier dysfunction disease?
- improper skin stacking
- improper secretion of lipids
- improper adherence of keratinocytes