T cell development Flashcards
Epithelial component of the thymus
Develops bilaterally from the third pharyngeal pouch at 4 weeks gestation
When does the thymus split from the pharynx?
Between weeks 4 and 7
When is the thymus colonized with hematopoietic stem cells?
7th week
When does the thymus produce T cells?
12th week
When do T cells leave the thymus?
13th week
DiGeorge syndrome
Deletion in the 22nd chromosome; complete T cell deficiency and severe immunodeficiency
FOXN1 gene
On chromosome 17. Codes for a transcription factor necessary for maturation of T cells
Thymic epithelial cells
Produce cytokines important for growth and differentiation
Expresses notch receptors that are crucial for T cell lineage commitment
Expression of peripheral tissue antigens
Corticomedullary junction of the thymus
Where dendritic cells and macrophages reside for antigen presentation and phagocytosis of self-reactive T cells
What CD marker is present on the hematopoietic stem cells in the thymus?
CD34
Four developmental events in T cell maturation
T lineage commitment
Proliferation and differentiation
Selection
Maturation
Persistent Notch signaling
Commits T cells to the lineage; short signaling can cause NKT development OR T cell development
Notch ligands
DL-1 and DL-4
What happens once T cells commit to the lineage?
Express CD1, recombine delta, gamma, beta genes
What is required for recombination of T cells?
RAG-1 and RAG-2, as well as IL-7
How is recombination terminated?
Through ERK after signaling by preTCR
PreTCR is mediated by what?
CD3 with preT-alpha
Beta selection
Cell gets checked for a functional preTCR and if it works, then it massively proliferates; if it doesn’t, it dies
What skews the T cells toward alpha-beta instead of gamma-delta?
The presence of pTalpha
Two dominant gamma-delta T cells
Delta-1 with various gamma genes
Gamma-9 delta-2
What do delta-1 T cell receptors do?
The first to emerge from the fetus
Colonize in epithelial cells
Recognize stressed cells and lipid signals presented by CD1B and CD1C
CD1 transmembrane proteins
Distantly related to MHC; there are four. A, B, C, and D
What do CD1B and CD1C associate with?
Beta-2 microglobulin
What do TCRgamma2delta9 cells do?
Recognize non-peptide phosphor antigens on mycobacterium and malaria, release IFNgama
What co-stimulant is required for development of NKT cells?
CD1D
What are the CDs expressed by NKT cells?
Either CD4 positive or double-negative, with CD56 and TCRalpha-beta/CD3 complex
What do NKT cells do?
Release Th1 and Th2 cytokines
Function of Treg cells
Help in the negative selection process
What is the selection process mediated by Treg cells called?
Dominant tolerance
CDs on Treg cells
CD4 and CD25
What signals for peripheral generation of Tregs?
TGF-beta
FOXP3
Necessary for the production of Tregs in the thymus
