T-Cell Development and Selection (Exam III) Flashcards
T cell life cycle
T cell precursors travel from the bone marrow (undifferentiated state) to develop in the thymus (all of selection, and formation of T cell receptor and testing of it).
Mature T cells leave the thymus and travel to secondary lymphoid organs where they can search for the antigen they are specific for
Thymic involution
Thymus goes through involution.
0-10 years old, thymus is in its full funciton, but as humans age, the thymus becomes smaller and has less function
T cells are called _ while they wait to develop into T cells
thymocytes
When stem cells move from the bone marrow to the thymus, they begin their transformation
uncommitted progenitor cell -> double negative thymocyte comitted to the T cell lineage
When stem cells enter the thymus
- Express CD34 (stem cell marker) as they enter the thymus, and eventually they downregulate CD34 and begin to upregulate CD2
Early developmental phenotype.
CD2 (after CD34)
Adhesion and signaling
CD2 signals that the cell is comitted to the T cell lineage.
TCR genes
Antigen receptor
Uncommitted to T cell: germline
Committed to T cell: beginning rearrangement
CD4 and CD8 are not expressed, in either
uncommitted stage or the committed stage.
T cell selection happens in
the thymus
Regions of the thymus
Cortex - very dense
Medulla - less dense
region between medulla and cortex
cortico-medullary junction
Cortex houses what cells?
- Cortical epithelial cells
- Thymocyte (cells that undergo the selection process)
- Medullary eptithelial cells
Thymic epithelial cells perform
positive selection (happens in the cortex)
where does positive selection occur
cortex of thymus
where does negative selection occur
cortico-meduallar junction region of the thymus
cells that mediate negative selection of thymocytes
- Dendritic cells
- Macrophage
cortical epithelial cells origin
thymic origin
thymocyte origin
bone marrow origin
medullary epithelial cell origin
thymic origin
dendritic cell origin
bone marrow origin
Macrophage origin
bone marrow origin
cells that undergo T cell selection
thymoctyes
The early development of a;b T cells in the thymus
- progenitor cells
- proliferation
- double (-) T cells commit to T cell lineage
- Rearrange beta genes
- CHECKPOINT for pre-TCR
- proliferating double (-) pre-T cells
- immature double positive cells rearrange alpha genes
- CHECKPOINT for TCR
- mature double positive cells
After a productive rearrangement..
First: Positive selection
- Thymic epithelial cells do the selecting (Thymic origin)
- Poor binders eliminated (If the T cell receptor does not bind to MHC, the T cell dies).
- Positive selection is happening when the T cell receptor is able to bind to MHC.
- Region of thymus: Cortex
Opposite in B cells, they first undergo negative selection.
Second step after rearrangement
Negative Seletion
- Dendritic cells do the selecting (bone marrow)
- Overly strong binders eliminated
- Region: corticomedullary junction
Do gamma/delta cells go through negative or positive selection?
No
no regulation of if they bind MHC or too tightly to a cell.
What step determines if a a T cell will commit to the CD4 or CD8 phenotype
positive selection
If a TCR happens to interact with a MHC class I molecule with reasonable affinity during positive selection
the CD8 molecule will join that interaction and downregulate CD4 and signal the formation of a CD8 T cell
If a TCR happens to bind MHC class II with reasonable affinity
CD4 joins the interaction and will send a signal to the T cell and upregulating CD4 and downregulate CD8, becoming a CD4 cell.
during positive selection the T cell goes from being _ to _
double positive to single positive
Either CD4/CD8 is upregulated, while the other is downregulated
CD4-, CD8- (first step)
Stage in Development:
- proliferation and differentation to double positive CD3+ thymocytes
Thymocyte location:
- double negative CD3- thymocytes in the subcapsular zone
CD4+,CD8+ (second step)
Stage in development:
positive selection
Thymocyte location
- double positive thymocytes in the thymic cortex
CD4+, CD8+ (third step)
Stage in developemnt:
- Negative selection
Thymocyte location and characteristics
- Double positive CD3+ thymocytes throughout cortex and especially at the cortico-medullary junction
Either CD4+ only or CD8+ only
Stage in development
- Entry to circulation
Thymocyte location and characteristics
- mature self-restricted, self-tolerant, single positive CD4 or CD8 T cells leave the thymus in blood venules
