Week 4: T Cell Development Part 1 Flashcards
Where do T cells derive from?
Common lymphoid progenitors (CLP) in the thymus
What is the function of T cells?
- Recognizes peptide antigens in context of MHCs
- Involved in adaptive immunity
- Mediates cellular immunity
How are T cells involved in adaptive immune response?
- Acquired immunity
- Highly specific
- Requires an educational process
What are the lineages of T cells?
ab T cells (majority) and gd T cells (5%)
Describe the development of the thymus?
- Fully developed at birth
- 1 year after birth the thymus degenerates and replaced with fat
- Decreases steadily with age: involution of the thymus
Describe the development of T cells?
- Early T cell precursor (CLP) development occurs in the bone marrow
- Precursors leave the BM and and travel through the blood to the thymus where they go through selection and educational processes
- Mature T cells leave the thymus and travel to secondary lymphoid tissues
How do progenitor cells differentiate to T cells?
- Not committed to T lineage when they enter the thymus
- Interacts with thymus stroll cells, progenitor lose their stem cell surface proteins/receptors and become thymocytes
What are thymocytes?
Immature T cells that lack TCR but begin to rearrange their TCR genes (double negative thymocytes DN)
What develops a T cell?
Thymus stromal cells produce growth factors and glands that contribute
What factors and ligands are released by the thymus stromal cell?
IL-7
What is Notch 1?
Receptor of progenitor cell that binds to signals to commit it to T lineage
What is IL-7?
Growth factor that is secreted by thymic stromal cells and binds to the IL-7R on T cell progenitors to induce progenitor into DN thymocyte
Does the TCR bind to MHC Class 1 and 2 strongly?
No: death
Yes: survive
Does he TCR bind with low or high affinity to self-antigen on MHC?
Low: survive
High: death
In what ways are T cells screened to make sure TCR is functional?
Checkpoint 1: is b chain functional
Checkpoint 2: is a chain functional
Describe the process of gene arrangement of ab T cells?
- The first rearrangement is b chain, producing a functioning b chain and a surrogate a chain
- When a b chain is produced, it forms a complex with CD3
- TCR complex undergoes a chain rearrangement
- Once complete TCR is formed, the cell expresses both CD4 and CD8 TCR co-receptors and is considered double positive (DP)
Where does positive selection occur?
The cortical region of the thymus
What is purpose of positive selection?
Ensures MHC restriction
What occurs during positive selection?
- DP T cells interact with cortical epithelial cells that have both MHC class 1 and 2 molecules
- If the DP TCR binds to the MHC, then it is positively selected
- if the DP TCR is unable to bind to MHC, the cell undergoes apoptosis
What happens to thymocytes that are positively selected?
Induced to become single positive T cells (SP)
Describe the difference between DP cells binding to MHC class 1 and 2?
1: Induction to become CD8+ cytotoxic T cell
2: Induction to become CD4+ helper T cell
Where does negative selection occur?
Medular region of the thymus
What occurs during negative selection?
- DP cells progress to SP
- Eliminates potentially harmful thymocytes that have high affinity TCRs for self peptides
What can undergo negative selection?
- Interaction of positively selected thymocyte with epithelial cells, macrophages, and DCs that present self-antigen
- Only thymocytes whose TCR have low affinity for MHC molecules on APCs are selected
