Flashcards in T cell development Deck (18):
tolerance to self antigens that is established in lymphocytes developing in central or primary lymphoid organs
mainly achieved by clonal deletion
elimination of immature lymphocytes when they bind to self antigens which produce tolerance of self.
chemoattractant cytokine that stimulates the migration and activation of cells
failure to develop thymic epithelium. parathyroid glands are absent and there are anomalies in the large blood vessels
during intrathymic development, thymocytes that recognize self are deleted from the repertoire
only those developing T cells whose receptors can recognize antigens presented by self MHC molecules can mature in the thymus.
general process by which cells perceive changes in their environment.
produces chemotactic factors that attract T cell progenitors
double negative, least mature T cells, considerable cell division, undergoes gene rearrangment for TCR beta/gamma/delta, least plentiful, is located in the outer cortex
double positive, TCR alpha rearrangement, most plentiful, located in the inner cortex
CD4+CD8- or CD4-CD8+
single positive, most are mature cells with high levels of CD3 and TCR beta. There are twice as much CD4 than CD8 in the medulla. Most single positive cells leave the thymus.
Single Positive with low CD3 and TCR beta
immature (ISP), transitional cells that are on the way from DN to DP.
First Checkpoint (Beta selection)
asseses whether TCR beta chain is functionally rearranged
mediated by pre-TCR, involves RAG, CD3 epsilon, TCR beta, pT alpha.
if you knock out RAG genes, can't make TCR, blocked at double negative stage
Second Checkpoint (positive/negative selection)
assesses whether TCR alpha is functionally rearranged, whether TCR is self MHC restricted, whether the TCR is auto-reactive.
mediated by mature alpha beta TCR. involves TCR alpha, MHC Class 2, beta 2 microglobulin, bare lymphocyte syndrome
knock out TCR alpha, blocked at DP stage, unable to make SP.
cells that promote positive selection
cortical epithelial cells
cell types that can induce negative selection
thymic DC, cortical epithelial cells, medullary epithelial cells
cells that cannot induce negative selection