T Cell Development Flashcards
Where does T cell development take place?
Thymus
What are the phases of T cell development that take place in the thymus?
Maturation
Cell proliferation
TCR gene rearrangements
Cell apoptosis
What are the two methods of T cell selection?
Positive and negative
What is DeGeorge’s syndrome?
Chromosomal disorder leading to decreased T cells
What pharyngeal pouches does the thymus come from?
3rd pair
What are the pouches made out of?
endoderm
What are the clefts made out of?
exoderm
What forms the capsule around the thymus?
Mesenchyme
What is the cellular organization of the thymus?
1- subcapsular region
2- cortex
3- corticomedullary junction
4- medulla
Where are hassall’s corpuscles located?
in the medulla of the thymus
Is the cortex or the medulla more dense?
the cortex
What type of cells travel to the thymus?
T cell precursors (prothyrocytes)
Where do prothyrocytes come from?
Fetal lever and bone marrow
Where do prothyrocytes enter the thymus?
at the cortico-meduallary junction
How do the prothyrocytes enter the thymus?
blood vessels
What signals are used to get the prothyrocytes to the thymus?
chemotactic substances control prothyrocyte travel
What are the most immature T cells? What do they express?
The least mature are double negative t cells that have just migrated from the bone marrow
Do double negative’s express the TCR?
Some do, but about 2/4 are triple negative
What type of somatic rearrangement occurs at the DN stage?
gamma, beta and delta. NOT alpha
What does gamma pair with? What does alpha pair with?
gamma pairs with delta and alpha pairs with beta
What are double positive T cells?
express both CD4 and CD8
when does alpha somatic rearrangment occur?
at the DP stage
When does the most apoptosis of T cells occur?
At the DP stage because dp’s are bery sensitive to anything that can cause apoptosis
What are single positives?
DP’s that have down regulated one of the two co-receptors
Which is more prevalent, CD4+ or CD8+?
CD4+
What gets turned on first, CD4 or CD8?
CD4
What is it easier to become? AB or DG?
Alpha beta
A precursor cell that comes to the thymus is destined to become what?
dendritic cell, B cell or T cell. The cell needs to chhose the T cell lineage
SInce beta and alpha rearrangements occur at different times, what does beta pair with?
a surrogate alpha chain so some rounds of proliferation can occur before teh alpha chain is rearranged
Where does DP selection happen?
inner corted
When a cell has committed to either CD4 or CD8 where does it go within the thymus?
The medulla
What is the first T cell checkpoint?
Beta selection. It is to assess whether TCR beta is functionally rearranged
If a cell passes beta selection, what proceeds?
Proliferation and expression of CD4 and CD8 and termination of TCR gamma expression. Alpha rearrangement begins as well
What is the second T cell checkpoint?
positive and negative selection
what is the purpose of the second t cell checkpoint?
1- assess whether TCR alpha is functional
2- assess whether TCR is self MHC restricted
3- assess whetherTCR is auto-reactive
If there is no reaction with the peptide/ MHC?
The cell dies by neglect
What is positive selection?
The cell needs to bind MHC and self peptide just enough. I it binds too much or too little is will die via apoptosis
What causes peripheral ligands to be expressed in the medullary epithelial cells?
Aire transcription factos
What cells mediate positive selection?
cortical epithelial cells
What cells mediate negative selection?
any cell can mediate it
