T Cell Development Flashcards
What is CD3?
Nonvariable subunits within TCR
What is DiGeorges syndrome?
genetic immunodeficiency in which there is a failure to develop thymic epithelium (no T lineage cells)
What is a nude mouse?
defect due to loss of transcription factor involved in thymic epithelial cell differentiation
What is thymic involution?
decreased output of thymus as you get older
Where do cells that seed the thymus come from and enter?
Prothymocytes from fetal liver and BM enter the thymus via blood vessels at the cortico-medullary junction
What produces chemotactic factors that attract T cell progenitors?
thymic anlage/rudiment
What controls thymocyte egress from the thymus? Where do they leave from?
- controlled by chemokines and sphingosine 1-phosphate receptors (lipid chemoattractant)
- leave from venules in medulla
What is central tolerance?
tolerance to self-antigens that is established in the T cells developing in the central or primary lymphoid organs (thymus and BM)
What is clonal deletion? What is it the main mechanism of? What is another name for it?
- elimination of immature T cells when they bind self-Ag
- central tolerance
- negative selection
What is positive selection?
only T cells whose receptors can recognize ag presented by self-MHC can mature
What rearrangments occur at DN stage?
TCR beta, gamma, and delta
What stage does TCR alpha rearrangement occur at?
double positive
What stage does positive and negative selection occur at?
double positive, after alpha rearrangment
Which are the most mature T cells?
single positive cells, high levels of CD3 and TCRbeta
What is the ratio of CD4 to CD8 cells?
2:1
What are the single positive cells that have low levels of CD3 and TCR beta?
immature single positives, in transition between double negative and double positive
What is the first check point in T cell development?
beta selection
- assesses whether TCR beta chain is functionally rearranged
- proliferates, expresses DP, terminates gamma locus, and initiates alpha locus
Will a double positive thymocyte ever express alpha-beta, and gamma-delta?
No, once you rearrange one there is no reason to rearrange the other
What is the second check point in T cell development?
positive and negative selection
- assesses whether TCR alpha is functionally rearranged and whether TCR is self-MHC restricted or auto-reactive
- DP goes to single positive with high TCR alpha levels
What is death by neglect?
absence of interaction with DP thymocytes causes apoptosis since they need signal to survive
If you knockout RAG, what stage are T cells stopped at?
double negative
If you knockout B2 microglobulin, what cell type do you not make?
CD8
What important process is mediated by AIRE?
-tissue-specific Ag from other parts of the body (peripheral Ag) are expressed in thymic epithelial cells in the medulla so T cells that respond to them can be destroyed
Where does positive selection occur?
cortex of the thymus
