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29 Cards in this Set
- Front
- Back
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thymocytes
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developing t cells in the thymus; from them comes functionally distinct subpopulations of mature tcells
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positive selection
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selects FOR tcells that have receptors capable of recognizing ONLY SELF MHC
Generates self-mhc restriction |
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Negative selection
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selects FOR cells that don't react too strongly with self MHC or self-MHC presenting self Ag.
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when pre-Tcells arive at thymus, do they have CD4, CD8, CD3 complex, or TCR?
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NO
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what do Tcell precursors do when they get to the thymus?
what are these early cells called? |
enter outer/paracortex and proliferate.
DOUBLE-NEGATIVE CELLS |
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2 alternative pathways for double-negative thymocytes to progress down:
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gamma-delta; v. few do <5%
or Alpha-beta - most do. |
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WHAT makes Tcell population diverse?
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-Junctional diversity (during rearrang)
-Random gene rearrangement |
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what percentage of thymocytes die in the thymus? what's the mechanism?
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98%, by apoptosis
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what type of cells determine the haplotype of MHC that will restrict the Tcells for self-MHC-restriction?
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stromal cells in the THYMUS - where development occurs, positive selection
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thymic stromal cells include:
their function is to: |
-epithelial cells
-macrophages -dendritic cells express both MHC class 1 and 2!! so interaction with immature thymocytes results in pos+ and neg- selection. |
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+ selection ensures
- selection ensures |
MHC RESTRICTION
SELF TOLERANCE |
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generation of TCR diversity gives approx how many different Tcells?
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junctional variation and rearrangement give 10^15-18 differnt TCRs!
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Where does:
Positive selection take place |
thymic cortex
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where does:
negative selection take place |
thymic medulla
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what is produced by the first DNA rearrangement of Tcells
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cells go down alpha/beta or gamma/delta pathways.
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what happens to the gamma/delta population of Tcells after differentiation as thymocytes
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they increase and develop, then decline
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how do ++ cells become CD8+ or CD4+?
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interact with MHC1 = CD8+
interact with MHC2 = CD4+ |
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remember how alpha chains of TCR wait to so that different ones can be expressed with the B chain? how does that help positive selection?
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because multiple a/B complexes, better chance that some will pass the test and bind self-MHC, thus not apoptose.
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2 thymic selections; which takes place where?
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positive - cortex - for selfmhc react.
negative - medulla - for self-peptide autoimmunity prevention. |
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what does the instruction model refer to
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after maturation/gene rearrangement,etc, double positive cells become single CD4 or CD8.
Determining Factor: they are influenced by MHC1 or MHC2 |
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components of the cascade of signal transduction (triggered by ag/mhc/tcr binding)
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-Tyrosine kinase
-Phosphorylase kinase Calcium Small G proteins |
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2 signals for Th cell activation:
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Signal one: peptide/mhc binds to Tcr
Signal two: CD28 binding to B7 on APC (Co-stimulatory signal) |
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what 3 gene products are expressed after SIGNAL ONE in Th cell activation:
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1. Transcription factors (turn other genes on)
2. Cytokine/Cytokine receptors (activate self and others) 3. Adhesion molecules (help TcR) |
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what binds to cytoplasmic domains of CD3 after signal one?
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tyrosine kinase; phosphorylates ITAM on intracellular domain. initiates signal cascade for Tcell activation!
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Tcells recieve
only signal one: what happens? both signals: what happens? |
1. Go into clonal anergic state
2. go into clonal expansion! |
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co-stim signal is active in WHO, when?
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in professional APC (dendritic) ALL THE TIME; constitutive.
in Bcells and macrophages: only when ACTIVATED! |
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AICD: what is it, how its activated.
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Activation Induced Cell Death;
When Tcell is activated, Fas is expressed and Fas-ligand binding stimulates apoptosis. Glucocorticoids also stimulate it; treatments SHRINK thymus |
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Super Ag: exo or endotoxin?
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EXOTOXINS; lead to TSS, systemic shock.
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special note about gamma/delta TcR cells
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can bind Ag without MHC presentation; in skin epithelium. protect epithelial cells, remove dead cells
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