Term
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Definition
- Two different types of TCR
- Alpha/Beta or Gamma/Delta
- CD4 T cells (Alpha/Beta)
- CD8 T cells (either AB or GD)
- AB more abundant
- All are CD3+
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Term
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Definition
- Progenitor cells - bone marrow
- Progenitors move to thymus to develop
- Get signals which allow them to keep going down the differentiation pathway towards becoming a mature, naive T cell that can protect from infections
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Term
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Definition
- T-cell precursors travel from the bone marrow to develop in the thymus
- Mature T cells leave the thymus and travel to secondary lymphoid tissues
- In the absence of activation by specific antigen mature T cells continue to reciruclate between blood, secondary lymphoid tissues and lymph
- GALT (gut associated lymphoid tissues)
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Term
| The Cellular Organization of the Thymus |
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Definition
- Thymic origin: cortical epithelial cell, medullary epithelial cell
- Bone Marrow Origin: Thymocyte, DC, Macrophage
- Macrophages (cortex/medulla): remove the many thymocytes that fail to mature properly
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Term
| The Cellular Organization of the Thymus |
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Definition
- Scanning EM of the Thymus
- Developing thymocytes (spherical cells) occupy the interstices of an extensive network of epithelial cells
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Term
| Thymic function and size decreases with age |
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Definition
- Starting at birth, the T cell producing tissue in thymus is gradually replaced by fatty tissue.
- This process is called involution of the thymus
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Term
| Stage In Development - Thymocyte Location & Characteristics |
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Definition
- Proliferation and differentiation to DP (+) CD3+ thymocytes
- DN (-) CD3- thymocytes in the subcapsular zone (CD4- and CD8-)
- Positive Selection
- DP CD3+ thymocytes in the thymic cortex (CD4+/CD8+)
- Negative Selection
- DP CD3+ thymocytes throughout the cortex and especially at the cortico-medullary junction
- Entry to the circulation
- Mature self restricted, self tolerant SP CD4 or CD8 leave the thymus in blood venules
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Term
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Definition
- Progenitor enter thymus (1st phase)
- Now at DN stage, no CD4 or CD8 expression, no TCR expression
- This stage rearrangement of TCR genes occurs (VDJ recomb.) but only at either gamma, delta, or beta genes no alpha
- The pre-Talpha chain dimerizes with newly rearranged beta chain, associated with CD3, moves to cell surface to form pre-TCR
- pre Talpha chain - germline encoded, not rearraged
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Term
| Pre-TCR, Pre-Talpha, TCR B |
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Definition
- Signals
- Cells become permissive for TCR alpha chain locus arrangement
- Stimulates expression of CD4/CD8 co-receptors
- Stimulates proliferation
- Stops additional TCR beta chain locus arrangements (allelic exclusion)
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Term
| Pre-T Cell Receptor & T Cell Receptor |
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Definition
- Comparison of structures of pre-TCR and TCR
- Only difference is that alpha cahin of TCR is replaced by preTalpha cahin in preTCR
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Term
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Definition
- Allelic exclusion: productive TCR beta chain rearrangement made -> stops Beta chain rearranging
- Pre TCR = go ahead signal to rearrange TCR alpha chain
- Cells upregulate both CD4 and CD8, now in DP stage where the alpha chain gets rearranged
- Now they go through thymic selection (DP to SP)
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Term
| Thymic selection/Thymus University |
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Definition
- Thymic selection teaches cells what they can and cannot react against
- Because of the diversity of the TCR generated through random gene rearrangemet, many T cells may not recognize your own MHC
- May be reactive against your own proteins - (self recognition)
- SO - need to select against cells that DO recognize your MHC and DO NOT recognize self proteins
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Term
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Definition
- Make sure T cells can recognize your own MHC (MHC Restriction)
- Cells that fail positive selection eliminated via apoptosis
- T cells now become SP as they express either CD4 or CD8 due to MHC II or MHC I interactions
- Important for autoimmunity
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Term
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Definition
- Rearrangement of TCR genes
- Death by apoptosis: do not interact with MHC
- Positive Selection of cells binding MHC
- Binds MHC I or II
- MHC I or II
- Epithelial cells
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Term
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Definition
- High affinity for own MHC + self peptide are deleted
- Primary mechanism of self tolerance and is called central tolerance - eliminated via apoptosis
- Low/Mod. affinity - live
- 90% of thymocytes die during (+) and (-) selection
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Term
| AIRE: Autoimmune Regulatory Element |
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Definition
- Transcription factor that promotes presentation of tissue restricted antigens in the thymus to then use these self antigen in thymus for negative selection
- AIRE (-/-) mice develop autoimmunity
- APS-1 (Autoimmune Polyendocrinopathy Syndrome)
- lack functional AIRE gene
- APECED (Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy)
- lack functional AIRE gene
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Term
| Effect of MHC I or II deficiency on thymocyte pop. |
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Definition
- CD4-CD8-
- Control (+), MHC I def. (+), MHC II def. (+)
- CD4+CD8+
- Control (+), MHC I def. (+), MHC II def. (+)
- CD4+
- Control (+), MHC I def. (+), MHC II def. (-)
- CD8+
- Control (+), MHC I def. (-), MHC II def. (+)
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Term
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Definition
- Transgenic animals and T cells where all CD8 T cells only have 1 specificity; in this case specific for flu Ag
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Term
| The early development of Alpha:Beta T cells in Thymus |
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Definition
- Early development of alpha:beta T cells in thymus from uncommitted progenitor cell to a DP cell bearing a Alpha:Beta TCR
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Term
| Positive selection of alpha:beta T cells by cortical epithelial cells in the thymus |
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Definition
- T cells with a TCR that binds to a self MHC I on
- Thymic cortical epithelial cells
- Macrophages
- Other cells in thymus
- Are signaled to survive and proceed to (-) selection
- T cells with a TCR that binds no self MHC I are signaled to die - apoptosis
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