THE IMMUNE SYSTEM – PARHAM 4TH EDITION
CHAPTER 7
T lymphocyte cells originate from the bone marrow but mature in the thymus.
Two lineages develop from a common T-cell precursor
α:β T cells
γ:δ T cells
The thymus is a primary lymphoid organ which gives rise to thymocytes in the thymic stroma = epithelial cells.
The thymus does not receive lymph; T-cells enter via the blood.
Embryological development thymus
1) The thymic anlage is formed from:
Ectoderm " epithelial cells of the cortex
Endoderm " epithelial cells of the medulla
2) Progenitor cells from the bone marrow colonize the thymic anlage.
3) Progenitor cells " thymocytes and dendritic cells
(DCs reside in medulla).
4) Bone marrow-derived macrophages colonize thymus.
5) T-cell progenitors differentiate and move to medulla.
The thymus degenerates after birth = thymic involution. Fat cells replace original cells as you grow older.
Thymic involution and thymectomy do not impair T-cell immunity: they are long-lived.
DiGeorge syndrome is a genetic disease where the thymus fails to develop. T-cells are absent, but B-cells present.
Patients have opportunistic infections and no adaptive immune system.
T-cell development
Lineage commitment
1) The T-cell progenitor cells express CD34 and other glycoproteins that characterize stem cells.
2) CD34 is replaced with CD2 (adhesion) and CD5 (glycoprotein) – after differentiation in the cortex.
The T-cells express neither CD4 or CD8 = double-negative T-cells or DN T-cells.
3) Race of gene rearrangement: β, γ and δ loci start at same time.
The T-cells express both CD4 and CD8 = double-positive T-cells or DP T-cells.
4) β first? α rearrangement continues, as well as γ:δ (another race!). ).
5) α:β first? T-cell commits to the α:β lineage!).
Commitment to β is favored:
Need only 1 functional rearrangement (γ:δ needs 2).
Has two Cβ loci per chromosome; if one is dysfunctional, 2nd loci can be used and (associated D and J segments).
!). Cells that fail productive rearrangement (98%) die by apoptosis and are eaten by macrophages in the cortex.
CHAPTER 7
T lymphocyte cells originate from the bone marrow but mature in the thymus.
Two lineages develop from a common T-cell precursor
α:β T cells
γ:δ T cells
The thymus is a primary lymphoid organ which gives rise to thymocytes in the thymic stroma = epithelial cells.
The thymus does not receive lymph; T-cells enter via the blood.
Embryological development thymus
1) The thymic anlage is formed from:
Ectoderm " epithelial cells of the cortex
Endoderm " epithelial cells of the medulla
2) Progenitor cells from the bone marrow colonize the thymic anlage.
3) Progenitor cells " thymocytes and dendritic cells
(DCs reside in medulla).
4) Bone marrow-derived macrophages colonize thymus.
5) T-cell progenitors differentiate and move to medulla.
The thymus degenerates after birth = thymic involution. Fat cells replace original cells as you grow older.
Thymic involution and thymectomy do not impair T-cell immunity: they are long-lived.
DiGeorge syndrome is a genetic disease where the thymus fails to develop. T-cells are absent, but B-cells present.
Patients have opportunistic infections and no adaptive immune system.
T-cell development
Lineage commitment
1) The T-cell progenitor cells express CD34 and other glycoproteins that characterize stem cells.
2) CD34 is replaced with CD2 (adhesion) and CD5 (glycoprotein) – after differentiation in the cortex.
The T-cells express neither CD4 or CD8 = double-negative T-cells or DN T-cells.
3) Race of gene rearrangement: β, γ and δ loci start at same time.
The T-cells express both CD4 and CD8 = double-positive T-cells or DP T-cells.
4) β first? α rearrangement continues, as well as γ:δ (another race!). ).
5) α:β first? T-cell commits to the α:β lineage!).
Commitment to β is favored:
Need only 1 functional rearrangement (γ:δ needs 2).
Has two Cβ loci per chromosome; if one is dysfunctional, 2nd loci can be used and (associated D and J segments).
!). Cells that fail productive rearrangement (98%) die by apoptosis and are eaten by macrophages in the cortex.
