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T-cells - Coggle Diagram
T-cells
T-cell mediated immunity
T-cel Circulation and Lymph node migration
Mature Naive T-cells circulate in the blood after exiting the lymph
T-cells in the blood move into the lymph node (Secondary Lymphoid Organ) via High Epithelial Venules (HEV)
L-selectin binds to Glycam1 and CD34
LFA-1 is activated by CCR7
Activated LFA-1 binds to ICAM
Naive T-cell migrates into Lymph node
Chemokines act as signaling/homing device for T-cell migration into the Lymph
T-cell Activation and differentiation
Differentiation
Helper T-cells express CD4
Cytotoxic T-cells express CD8
Activation
T-cells recognize antigens presented to TCR by APCs
APC MHC class 2 binds to CD4 on a helper T-cell
Various types of effector helper T-cells
Can aid in B-cell activation
Production of IL-17 and bacterial/fungal defense
Can aid in macrophage activation and cell immunity
APC expressing MHC class 1 binds to CD8 on cytotoxic T-cells
Leads to T-cell mediated cytotoxicity
requires release of Perforins to form pores
Granzymes enter the pores and cause apoptosis
Complete T-cell activation require co-stimulatory binding from CD28 and B7
Development
Origins and the Thymus
T-cell precursors are released from the bone marrow
Transported to thymus to be committed to T-cell development
Precursors in the thymus are called thymocytes
Thymus functionality declines as humans age
Slowly becomes fattier
Less thymic epithelial cells available for precursors to bind to
NOTCH signaling is essential for commitment to development
Multiple layers, functions, and cells within the thymus
Cells
Dendritic Cells
Presents immature T-cells self antigens in negative selection
Thymic epithelial cells
Presents self antigens to T-cells in positive selection
Macrophages
Responsible for consuming/absorbing dead T-cells as a result of apoptosis
Layers
Cortex
Located just below the subcapsular epithelium
Serves as the main site for initial T-cell development
Plays a role in positive selection of T-Cells
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Medulla
Deepest layer of the Thymus
Site for negative selection of Mature T-cells
T-cells that bind too high affinity to self-MHC antigens are selected to undergo apoptosis
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Cells selected for survival undergo final processes of maturation and proliferation
Subcapsular epithelium
Outer most layer of the thymus
Serves as the initial site for thymocytes
Stages of Development
Double Positive Stage
Occurs in the Cortex
a-chain is rearranged
Has more attempts than b-chain (not known if it is limitless or just a higher number)
Success leads to a double positive expression
Both CD4 and CD8 are expressed
Failure leads to apoptosis
ab-TCR is expressed on the surface of the cell
Cells in this stage undergo positive selection
Positive selection
Cell does not recognize self-MHC
Apoptosis
Cell does weakly recognize self-MHC
Survival
Single Positive
Occurs in the medulla
Either CD4 or CD8 are expressed
The other is lost during negative selection
CD8 = Cytotoxic T-cell
CD4 = Helper T-cell
Negative selection
High affinity binding to self MHC leads to apoptosis
Success results in
Self-tolerance
Double Negative stages (DN1 - DN4)
Takes place in the Subcapsular zone
DN1
CD3, CD4, and CD8 are not expressed
DN2
CD3 is expressed between DN2 and DN3
DN4
Proliferation of T-cells with successful b-chain rearrangement
Undergoes Allelic exclusion to suppress further b-chain rearrangement
NOTCH signal is turned off
DN3
B-chain is rearranged
Each cell has 4 attempts to properly rearrange
Failure after 4 attempts leads to programmed cell death (
Apoptosis
)
Success leads to implementation of a surrogate a-chain