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Immuno 12/04/12 T Cell Lymphopoiesis
HDPP final at UMMSM
33
Immunology
Graduate
12/13/2012

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Cards

Term
What process begins T cell differentiation?
Definition
Commitment: rearrangement and expression of the TCR
Term
Where do commitment, TCR selection, and maturation take place?
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)
Term
What are thymocytes?
Definition
Developing T-cells
Term
What is the stroma?
Definition
Fibroblasts, epithelial cells, dendritic cells, and macrophages which provide necessary signals including soluble factors (cytokines) and molecules for intercellular interaction
Term
What is DiGeorge syndrome?
Definition
A disease of failed thymic development. Patients have little to no T-cell production
Term
What is special about the thymus?
Definition
It can be removed after birth without problems because the naive T cells are long-lived
Term
What happens in commitment?
Definition
Bone-marrow precursors enter the thymus. These make up <0.1% of thymic cells
Term
What are double negative T-cells?
Definition
About 5% of the T cells in the thymus which are CD4-CD8-
Term
What are double positive T cells?
Definition
About 80% of T cells that undergo expansion and receptor selection are CD4+CD8+
Term
What happens after double positive T cells are formed?
Definition
Cells are subjected to positive and negative selection, then mature and become single-positive T cells, about 15% of T-cells
Term
How long does T cell development take from entry into the thymus to movement to the spleen?
Definition
3 weeks
Term
How do lineages differentiate during commitment?
Definition
Rearrangement to TCR-gamma delta or TCR-beta
Term
What is the role of IL-7?
Definition
It induces Rag1/2 genes to cause differentiation and expansion
Term
What is X-linked SCID?
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
Term
Where are the TCR genes located?
Definition
TCR-a and TCR-delta are on the same loci; TCR-b and TCR-y are each on separate loci
Term
How do TCR-b cells proliferate?
Definition
They must first interact with a pre-TCR-a molecule to form a pre-TCR
Term
What are the results of TCR gene rearrangement?
Definition
TCR-b and TCR-yd
Term
What are TCR-yd?
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
Term
What are TCR-ab?
Definition
MHC-restricted T cells essential for afaptive T cell host defense.
Term
What rearrangements are more common in TCRs?
Definition
TCR-b product rearrangements are more common that TCR-y and TCR-d
Term
What happens in beta-selection?
Definition
A pre-Ta interacts with TCR-b and CD3 to form a pre-TCR molecule
Term
What is the result of formation of a pre-TCR molecule?
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
Term
What are the characteristics of immature T cells during receptor selection?
Definition
They are double positive and express Rag1/2 again
Term
What happens in positive selection?
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
Term
What is bare lymphocyte syndrome?
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
Term
What is negative selection?
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
Term
Which genes are MHC II? MHC I?
Definition
MHCII: HLA-DR, DP, and DQ
MHCI: HLA-A, B, and C
Term
What is AIRE?
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
Term
What happens to T cells that escape negative selection?
Definition
CD4+CD25+Foxp3+ Tregs suppress autoreactive T-cells by recognizing self-peptides and expressing ILR-2a
Term
How do Tregs develop?
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
Term
What is IPEX?
Definition
Foxp3 deficiency weakens immunity and multiple organs are fatally inflamed
Term
What are general characteristics of mature thymocytes?
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.
Term
How do mature thymocytes leave?
Definition
They leave venules and lymphatics at the cortical-medulary junction to enter the periphery
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