T-cell Maturation Flashcards
What are primary and secondary lymphoid organs?
Primary
- Bone marrow
- Thymus
Secondary
- Peripheral organs
- Lymph nodes
- Spleen
- Lymphoid tissue, etc.
B cells develop, mature and express antigen receptors in the ________
T cells develop, mature and express antigen receptors in the ________
Bone marrow
Thymus
What is the end goal of B cell and T cell maturation?
To produce a mature but naive lymphocyte that can leave the primary lymphoid organ and travel to the “periphery” where it will encounter and respond to foreign antigen
At what point do T-cells leave the Bone marrow and enter the thymus?
When does this happen in the life cycle of humans?
Common Lymphoid progenitors –> leave BM travel to Thymus
Before birth
Describe the structure of the thymus.
The thymus is bi-lobed. The tissue contains a section called the cortex and the medulla.
Describe how T-cells enter the thymus.
Via postcapillary venules between the cortex and medulla. CLPs express chemokine receptor 9 (CCR9) and the cortex excretes the ligand for this receptor, so the CLPs first move into the cortex. At a point during development in the cortex, the t-cell progenitors upregulate CCR7 which binds to ligands in the medulla, which stimulates the cells to move to the medulla after the cortex.
What are epithelioreticular cells?
What do they present on their surface?
They are epithelial/stromal like cells in the cortex and medulla that help instruct the T cell in how to develop (responsible for mediating positive and negative selection)
Present self-antigen on MHC I & II
Why are macrophage present in the thymus?
Because immature t-cells are undergoing development and there are multiple points during this process where they an undergo apoptosis so the macrophages are needed to clean up the debris.
What is the purpose of dendritic cells in the thymus? Where are these cells located within the thymus?
- They stimulate Treg cells
- Medulla
What is a hassall corpuscle?
A type of epithelioreticular cell that secretes IL-7, which stimulates the immature T cells to grow
The thymus is fully developed at birth.
True/False
True
When does thymic output of naive t cells ramp down?
~ 25 - 30 y/o
What does it mean if a t-cell is double negative?
It does not express CD4 or CD8
What is CD3?
CD3 is an important co-receptor for the T-cell receptor
How does a t - cell progress from being double negative to double positive?
Thymic stroma (ECR) cells signal DN t cells to rearrange their TCR genes via VDJ recombination. If the rearrangement is successful, the t cell survives and proliferates. If the rearrangement is unsuccessful then the t cell dies. Cells that survive this phase now have a function TCR and express CD3, CD4 and CD8 and are called double positive.
Positive Selection
- What is the goal of positive selection?
- Where does positive selection occur?
- How does the process of positive selection proceed?
- Double positive t cells are stimulated to mature into single positive cells (i.e. express either CD4 or CD8 but not both).
- Cortex of thymus
- ERC cells in cortex display self-peptides on MHC I and II. CD4 stabilizes binding to MHC II presenting cells and CD8 stabilizes binding to MHC I presenting cells. If the T-cell undergoes a weak interaction with MHCII then it will express CD4. If the T-cell undergoes weak interaction with MHCI then it will express CD8. If the T-cell does not bind to MHC or if it binds too strongly, then it will die via apoptosis.
Negative Selection
- What is the goal of this process in general?
- Where does this process occur?
- What molecule is expressed by ERC cells in this process?
- Describe how this process occurs.
- To ensure that t-cells that recognize self-antigen with high affinity undergo apoptosis.
- Medulla of thymus
- Medullary ERC express autoimmune response element (AIRE) which turns on expression of genes from all parts of the genome to educate T-cells using self-peptide
- Immature single positive (CD4 or CD8) t cells have moved into the medulla. They now bind to MHC I or MHC II on ERCs that are expressing self-peptide produced via AIRE. Any SP T-cells that bind with too high an affinity will undergo apoptosis.
What are Treg cells?
How do they develop?
T-cells that function to suppress effector functions of activated T-cells
During negative selection, a T-cell that binds to self-peptide with a high affinity can become a Treg cell by means that are not yet well understood.
What are the 2 kinds of Treg cells?
Natural - in thymus, specific for self-Ag
Induced - in periphery, specific for foreign and self Ag
What is immunologic tolerance?
What is central tolerance?
What is peripheral tolerance?
The failure to respond to antigen
Tolerance to self-antigens that are established while lymphocytes are developing in central lymhoid organs
Tolerance acquired by mature lymphocytes in periperhy
