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55 Cards in this Set

  • Front
  • Back
Main mechanism for central Tcell tolerance:
Negative selection in thymus
5 mechanisms for peripheral Tcell tolerance:
-Clonal deletion
-Regulatory Tcells
What achieves clonal deletion?
Fas/FasL killing
What chieves Inhibition?
CTLA4/B7 interaction
What achieves regulatory Tcells?
What is the basis for ignorance?
Anatomical barriers
What achieves anergy?
Lack of the costimulatory molecule B7
What are the special APCs in the thymus that present self peptides to naieve double positive Tcells?
Medullary epithelial cells
What does the fact that MHC Class II expression is highest in the medulla of the thymus tell us?
That the medulla is where negative selection occurs.
Where does positive selection occur?
In the cortex.
What is the highest level of maturity that most thymocytes reach in the thymus?
Double positive, expressing the complete TCR.
What % of double positive thymocytes fail positive selection? (bind too weakly)
Of the 20% of thymocytes that succeed positive selection, What percent of those survive negative selection?
So what % of thymocytes actually mature and get into the peripheral circulation?
Only 5%
What is a common manifestation of failure of self-tolerance?
What is Velocardiofacial syndrome?
DiGeorge's syndrome
What chromosomal deletion is associated with DiGeorge syndrome?
What are the symptoms of DiGeorge syndrome?
-Hypoplastic thymus
-Hypoplastic parathyroids
-Heart defects
-Cleft palate
-Neuropsychiatric problems
What problems are seen with the thymus in DiGeorge's syndrome?
-Unable to positively select enough T lymphs (lymphopenia)
-Unable to achieve successful negative selection (autoimmune)
What do aire Gene mutations result in?
What does Aire encode?
A transcription factor expressed at high levels in the thymus.
What type of inheritance is seen with aire Gene mutation caused disease?
Autosomal recessive
How many different mutations in the aire gene have been described?
Over 40
What specific cells express the aire protein?
Thymic medullary epithelial cells
What does aire protein expression allow thymic medullary epithelial cells to do?
Express tissue-specific proteins for the intestines, liver, brain, eye, and pancreas.
What are 2 ways that anergy is induced in peripheral tolerance?
1. Lack of B7
2. Presence of CTLA-4
What makes Tcells express CTLA-4?
Low levels of B7
What makes Tcells NOT express CTLA-4?
High levels of B7
What are 2 mechanisms of cell deletion in peripheral tolerance?
1. Death receptors
2. Apoptotic proteins
What induces death receptor expression on Tcells?
Repeated stimulation by self antigen
What are the death receptors on Tcells?
Fas and FasL
What is the result of Fas/FasL binding?
What is ALPS?
What is the mode of inheritance for ALPS?
Autosomal dominant
What are the characteristic findings of ALPS?
-Lymphadenopathy (nonmalignant)
-Autoimmunity against RBCs
-Hemolytic anemia
What is the HALLMARK of ALPS?
Large numbers of double negative Tcells in the peripheral blood.
What is the source of the double negative Tcells in the peripheral circulation in ALPS?
They are mature, AGED cells that escaped apoptosis
What are the important cytokines secreted by Tregs?
What are the effects of IL-10?
-Inhibits APC functions (decreased IL-12, B7)
-Inhibits macrophage activation
What are the effects of TGFbeta?
-Inhibits Tcell activation
-Inhibits macrophage activation
What gene is ESSENTIAL for Treg development in the thymus?
What do Tregs develop from?
A double positive Tcell
What happens if the foxp3 gene is absent?
What is the disease associated with mutated foxp3?
What is IPEX?
Immune dysregulation
What are the symptoms of IPEX?
-Bowel inflammation
What is the CD marker for BCells that is present throughout their lifespan?
What is the CD marker present on Bcells at the beginning of their life, in pro-B cells?
What are 2 characteristic markers of immature B cells?
IgM and CD19
What are the characteristic markers on mature B cells?
IgM, IgD, and CD19
What is the mechanism of central tolerance for B cells? Where?
Negative selection - in the bone marrow
What are the 2 ways that Bcells that fail negative selection are taken care of?
-Receptor editing
If a Bcell doesn't get self antigen presented to it during maturation in the bone marrow, what will it do?
Go to peripheral lymphoid follicles
How do mature Bcells achieve self tolerance in peripheral lymphoid organs?
By seeing Self antigen presented without the help of T cells, which causes anergy.
What will happen to Mature B cells that do see self antigen in peripheral lymphoid follicles, and are partially activatd by Tcells?
They will be excluded from the follicles and undergo apoptosis.