Receptor repertoire selection and CD4/CD8 lineage commitment Flashcards
how does t cells migrate to the thymus from the bone marrow
via chemokines like thymosin, thymotaxin, thymopoetin, thymic factors.
which type T cells are favoured during early fetal development
gamma delta
gamma delta T cells
• gamma delta T cells bearing specific receptors end up in skin (Vg5), gut (Vg2), uterus (Vg6), etc.
• gamma delta T cells are not MHC restricted!
• Antigen is recognized directly, more like an antibody
• In some cases ligands for the gamma delta TCR are self proteins upregulated under stress conditions
• In humans, circulating gamma delta cells recognize a
phospholipid antigen from Mycobacterium tuberculosis
• Play a role in cancer surveillance
What a DP Thymocyte Needs to Progress to
the SP Stage
- Functional TCRu chain rearrangement
- CD4 and MHC 11 (To be a CD4 cell)
- CD8, MHC 1 TAP (To be a CD8+ cell)
- ERK signaling
- Calcineurin signaling
overview of t cell development
rearrange beta chain
rearrange alpha chain
positive selection
negative selection
How are T cells negatively selected against
self-antigens not present in thymus?
The Transcription Factor Autoimmune Regulator (AIRE)
Mediates Ectopic Gene Expression In the Thymlc Medullary Stroma — other tissue specific genes.. .kidney, heart, liver, lungs, gut, apart from brain and testes
This is known as promiscuous gene expression — about 10% of all genes in thymus are expressed this way
This eliminates many self-reactive T cells
What follows t cell development
T cells that pass both positive and negative selection become conventional T cells
They migrate to secondary lymphoid organs looking for their target antigen
‘Immunological synapse’
If they encounter specific antigen, they get activated, proliferate and become effector T cells
Some become memory T cells
If they don’t find the target they, eventually die by apoptosis after period of circulation
