T Cell Maturation Flashcards
When does the maturation of B cells from progenitors occur?
Before birth in the foetal liver.
After birth in the bone marrow
Final steps completed in the spleen.
Where do the precursors of T lymphocytes emerge from?
Foetal liver before birth primarily precursors of gammadelta TCell Receptor (TCR)
Bone marrow primarily alphabeta TCR later in life.
They then circulare to the thymus to complete their maturation.
What signals induce expression of genes required for alphabeta TCR’s?
Notch1 anf GATA3
What are the major events of lymphocyte maturation?
Growth factor mediated commitment, proliferation.
Initiation of antigen receptor gene rearrangement
Selection of cells that express pre-antigen receptors
Selection of repertoire
Maturation of functionally distinct T and B cell subsets
Where do the major events of lymphocyte maturation occur?
Bone marrow
What does cortex region of the thymus do?
Proliferation of the thymus
What can you use cell lineage marker proteins for?
Immunophenotyping cells
Diagnostically
Cancer therapies can be antibodies against these
How does the thymus T cells mature?
It starts with double negative thymocytes (CD3-4-8-) and some will become CD4- and CD8- whilst others become CD4+ and CD8+.
What happens to CD8- and CD4- T cells?
They export to the periphery and stay there
What happens to CD4+ and CD8+ T cells?
Exported to the periphery and can identify an respond to danger or damage.
What MHC does CD8+ cells have?
MHC1
What MHC does CD4+ cells have?
MHC2
What drives maturation of T cells?
Transcription factors, epigenetic modifications and cytokines. To become CD4+ cells epigenetic changes must occur to silence the CD8+ gene and vice versa.
What do mutations in the human gene encoding the common gamma chain receptor shared by receptors do?
Gives rise to x-linked severe immunodeficiency (X-SCID) characterised block in T cell, NK cell and normal B cell development.
What does somatic recombination of the T cells lead to in the thymus?
Variable regions
What are T-cell receptors structurally similar to?
Ig encoded by homologous genes
What is the difference between Ig and T-cell receptors?
They have similar varaible regions but different J regions in the VDJ recombination Rag complex.
They also have more distinct junctions.
What do T-cells not undergo?
somatic hypermutation
How many TCR recombinations can arise?
1000000000000000000
The TCR complex is found where?
On the surface of the cell
What does surface expression of the TCR require assembly off?
TCR alpha: beta with signalling subunits of CD3
What is constant in TCR complexes despite the specificity?
CD3 proteins and zeta
What is the TCR complex required for and not involved in?
Signalling and not involved in antigen recognition
How does CD3 bind to TCR?
Through charge interactions in the transmembrane domains to form the TCR complex.
What happens if there is no TCR complex?
The cell undergoes apoptosis
What is DiGeorge Syndrome (SCID)?
This is an autosomal dominant disease caused by large deletion leading to a small or no thymus resulting in no mature T-cells and few B cells. This makes patients susceptible to mycobacterial, viral and fungal infections. T-cells improve with age.
What do matured but naive T cells subsets interact with\/
Innate immune cell in secondary lymphoid organs