Glossary of chpt 10
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- developing t cells in the thymus; from them comes functionally distinct subpopulations of mature tcells
- positive selection
- selects FOR tcells that have receptors capable of recognizing ONLY SELF MHC
Generates self-mhc restriction
- Negative selection
- selects FOR cells that don't react too strongly with self MHC or self-MHC presenting self Ag.
- when pre-Tcells arive at thymus, do they have CD4, CD8, CD3 complex, or TCR?
- what do Tcell precursors do when they get to the thymus?
what are these early cells called?
- enter outer/paracortex and proliferate.
- 2 alternative pathways for double-negative thymocytes to progress down:
- gamma-delta; v. few do <5%
or Alpha-beta - most do.
- WHAT makes Tcell population diverse?
- -Junctional diversity (during rearrang)
-Random gene rearrangement
- what percentage of thymocytes die in the thymus? what's the mechanism?
- 98%, by apoptosis
- what type of cells determine the haplotype of MHC that will restrict the Tcells for self-MHC-restriction?
- stromal cells in the THYMUS - where development occurs, positive selection
- thymic stromal cells include:
their function is to:
- -epithelial cells
express both MHC class 1 and 2!! so interaction with immature thymocytes results in pos+ and neg- selection.
- + selection ensures
- selection ensures
- MHC RESTRICTION
- generation of TCR diversity gives approx how many different Tcells?
- junctional variation and rearrangement give 10^15-18 differnt TCRs!
- Where does:
Positive selection take place
- thymic cortex
- where does:
negative selection take place
- thymic medulla
- what is produced by the first DNA rearrangement of Tcells
- cells go down alpha/beta or gamma/delta pathways.
- what happens to the gamma/delta population of Tcells after differentiation as thymocytes
- they increase and develop, then decline
- how do ++ cells become CD8+ or CD4+?
- interact with MHC1 = CD8+
interact with MHC2 = CD4+
- 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?
- because multiple a/B complexes, better chance that some will pass the test and bind self-MHC, thus not apoptose.
- 2 thymic selections; which takes place where?
- positive - cortex - for selfmhc react.
negative - medulla - for self-peptide autoimmunity prevention.
- what does the instruction model refer to
- after maturation/gene rearrangement,etc, double positive cells become single CD4 or CD8.
Determining Factor: they are influenced by MHC1 or MHC2
- components of the cascade of signal transduction (triggered by ag/mhc/tcr binding)
- -Tyrosine kinase
Small G proteins
- 2 signals for Th cell activation:
- Signal one: peptide/mhc binds to Tcr
Signal two: CD28 binding to B7 on APC
- what 3 gene products are expressed after SIGNAL ONE in Th cell activation:
- 1. Transcription factors (turn other genes on)
2. Cytokine/Cytokine receptors (activate self and others)
3. Adhesion molecules (help TcR)
- what binds to cytoplasmic domains of CD3 after signal one?
- tyrosine kinase; phosphorylates ITAM on intracellular domain. initiates signal cascade for Tcell activation!
- Tcells recieve
only signal one: what happens?
both signals: what happens?
- 1. Go into clonal anergic state
2. go into clonal expansion!
- co-stim signal is active in WHO, when?
- in professional APC (dendritic) ALL THE TIME; constitutive.
in Bcells and macrophages: only when ACTIVATED!
- AICD: what is it, how its activated.
- Activation Induced Cell Death;
When Tcell is activated, Fas is expressed and Fas-ligand binding stimulates apoptosis.
Glucocorticoids also stimulate it; treatments SHRINK thymus
- Super Ag: exo or endotoxin?
- EXOTOXINS; lead to TSS, systemic shock.
- special note about gamma/delta TcR cells
- can bind Ag without MHC presentation; in skin epithelium. protect epithelial cells, remove dead cells
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