Term
| What process begins T cell differentiation? |
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Definition
| Commitment: rearrangement and expression of the TCR |
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Term
| Where do commitment, TCR selection, and maturation take place? |
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Definition
Commitment takes place in the subcapsular region of the thymus.
Selection occurs in the cortex.
Maturation occurs in the medulla.
(Processing is from outside in) |
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Term
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Definition
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Term
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Definition
| Fibroblasts, epithelial cells, dendritic cells, and macrophages which provide necessary signals including soluble factors (cytokines) and molecules for intercellular interaction |
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Term
| What is DiGeorge syndrome? |
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Definition
| A disease of failed thymic development. Patients have little to no T-cell production |
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Term
| What is special about the thymus? |
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Definition
| It can be removed after birth without problems because the naive T cells are long-lived |
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Term
| What happens in commitment? |
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Definition
| Bone-marrow precursors enter the thymus. These make up <0.1% of thymic cells |
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Term
| What are double negative T-cells? |
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Definition
| About 5% of the T cells in the thymus which are CD4-CD8- |
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Term
| What are double positive T cells? |
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Definition
| About 80% of T cells that undergo expansion and receptor selection are CD4+CD8+ |
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Term
| What happens after double positive T cells are formed? |
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Definition
| Cells are subjected to positive and negative selection, then mature and become single-positive T cells, about 15% of T-cells |
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Term
| How long does T cell development take from entry into the thymus to movement to the spleen? |
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Definition
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Term
| How do lineages differentiate during commitment? |
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Definition
| Rearrangement to TCR-gamma delta or TCR-beta |
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Term
| What is the role of IL-7? |
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Definition
| It induces Rag1/2 genes to cause differentiation and expansion |
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Term
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Definition
| X-linked severe combined immunodeficiency disease is when a cytokine receptor gamma-c subunit is deficient, resulting in a lack of IL-7 signaling. No NK cells or T cells can form. Treat with precursor cells that express the yc chain |
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Term
| Where are the TCR genes located? |
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Definition
| TCR-a and TCR-delta are on the same loci; TCR-b and TCR-y are each on separate loci |
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Term
| How do TCR-b cells proliferate? |
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Definition
| They must first interact with a pre-TCR-a molecule to form a pre-TCR |
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Term
| What are the results of TCR gene rearrangement? |
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Definition
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Term
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Definition
| About 5% of T cells. They are not MHC-resticted so do not deal with selection. They are found mostly at epithelial surfaces with a relatively unknown function |
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Term
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Definition
| MHC-restricted T cells essential for afaptive T cell host defense. |
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Term
| What rearrangements are more common in TCRs? |
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Definition
| TCR-b product rearrangements are more common that TCR-y and TCR-d |
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Term
| What happens in beta-selection? |
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Definition
| A pre-Ta interacts with TCR-b and CD3 to form a pre-TCR molecule |
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Term
| What is the result of formation of a pre-TCR molecule? |
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Definition
It signals the cell to:
1) stop rearrangements
2) become permissive for TCR-a locus interaction
3) express both CD4 and CD8 co-receptors and
4) intensely proliferate
This is for TCR-b ONLY, not TCR-yd |
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Term
| What are the characteristics of immature T cells during receptor selection? |
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Definition
| They are double positive and express Rag1/2 again |
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Term
| What happens in positive selection? |
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Definition
| Only T cells that recognize self-MHC molecules can survive. The TCR-b cells have 3-4 days to rearrange TCR-a genes until it can react with self antigen. Only about 5% of immature double-positive TCR-ab cells react; the rest die |
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Term
| What is bare lymphocyte syndrome? |
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Definition
| No thymic epithelial cells or APCs express MHC class II because of a lack of transcription comples for mRNA expression, resulting in a deficiency of CD4 T-cells and generalized immunosuppression |
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Term
| What is negative selection? |
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Definition
| A mediator of self-tolerance where T-cells that react too strongly to self antigen are destroyed. DCs present self-peptides; cells that recognize MHC II become CD4, cells that recognize MHC I become CD8, and cells that recognize both or bind too strongly are destroyed |
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Term
| Which genes are MHC II? MHC I? |
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Definition
MHCII: HLA-DR, DP, and DQ
MHCI: HLA-A, B, and C |
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Term
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Definition
| And autoimmune regulator expressed by thymic medullary epithelial cells for central tolerance. It is a transcriptional activator that causes expression of hundreds of tissue-specific antigens that the T cells would otherwise not encounter before maturation |
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Term
| What happens to T cells that escape negative selection? |
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Definition
| CD4+CD25+Foxp3+ Tregs suppress autoreactive T-cells by recognizing self-peptides and expressing ILR-2a |
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Term
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Definition
| They start as double-positive cells that mature in the medulla and express Foxp3 for unknown reasons. IL-2 mediates their survival in the periphery |
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Term
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Definition
| Foxp3 deficiency weakens immunity and multiple organs are fatally inflamed |
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Term
| What are general characteristics of mature thymocytes? |
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Definition
| They express only CD4 or CD8 and have increased levels of TCRs. They have functional potential (cytotoxicity or cytokine release) and acquire homing receptors. |
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Term
| How do mature thymocytes leave? |
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Definition
| They leave venules and lymphatics at the cortical-medulary junction to enter the periphery |
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