Development of T Lymphocytes Flashcards
When does the thymus develop?
Very early during: the epithelial component begins to develop during the 4th week
What immune cells develop in the thymus?
T helper
Cytotoxic T cells
Natural Killer
T regulatory
From which pharyngeal pouch does the epithelial component of the thymus develop?
Third
At what week does the developing thymus begin to produce T cells?
12th-13th week
Mature T cells begin to egress the thymus during the 13th-14th week
What is DiGeorge Syndrome? What does it tell us about the thymus?
Rare congenital disease syndrome whose symptoms vary greatly between individuals but commonly include a history of heart defects, characteristic facial features and recurrent infection due to absence of the thymus and T cells
The absence of the functional thymus results in complete T cell deficiency and severe immunodeficiency- transplantation of an allogeneic thymus graft into patients rescues T cell deficiency.
This suggests that the thymus is required for proper T cell maturation
What other genetic disease affects proper T cell development?
FOXN1 mutations
Which cells make up the thymic stroma?
Thymic epithelial cells and fibroblasts
Where in the thymus are mature T cells found?
Medulla
Where in the thymus are developing T cells found?
Cortex
Where in the thymus are the blood vessels containing HEV’s found?
Cortical-medullary junction
Thymic epithelial cells provide what three critical functions for T cells?
1) Produce cytokines such as IL1, IL6, IL7 and SCF, TSLP that are required for growth and differentiation of various immature T cells
2) Expression of molecules such as ligands DL-4 and DL-1 for the notch receptor, required for T cell lineage development
3) Expression of MHC classes I and II controlling the selection of maturing T cells
All thymic epithelial cells are derived from what germ layer?
Endoderm
Where do macrophages and dendritic cells mature?
Bone marrow
Where are macrophages and dendritic cells found in high populations in the thymus?
Cortico-medullary junction
What is the role of macrophages and DCs in the thymus?
antigen presentation, deletion of autoreactive T cells (negative selection) and phagocytosis of apoptotic thymocytes
What marker is indicative of HSCs?
CD34
Upon entry to the thymus, how is the lineage potential of CD34 pos. cells restricted?
CD34 positive can ONLY become T cells once they enter the thymus
How does the activity of the thymus relate to the decline in immune response of the elderly?
The age-associated decline in the production of T cells is responsible for the decline in immune response in the elderly
Describe the role of Notch signaling in T cell development
The Notch receptor signal is essential for T cell lineage commitment of the CD34 positive HSC.
Signal through the notch receptor terminates the potential to commit to B and myeloid lineages (monocytes and DC). The cells have potential to become T or NK cells (T/NK). Persisting notch signaling terminates NK development.
What is the role of DL-1/DL-4? What cells express it? What cellular events occur in the developing T cell?
DL-1/DL-4 is the notch receptor ligand, expressed by the thymic epithelial cells.
Following notch signaling, cells commit to the T lineage, through the rearrangement of TCR gamma, delta and beta genes.
What can a developing T cell develop into following notch signaling?
Following notch signaling, preT cells may develop into either TCR gamma/delta or TCR alpha/beta cells.
This rearrangement of gamma, delta and beta genes requires the expression of RAG 1 and RAG 2
Which cytokine is required for the development of the preT stage?
IL-7