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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
-dendritic cells

express both MHC class 1 and 2!! so interaction with immature thymocytes results in pos+ and neg- selection.
+ selection ensures

- selection ensures

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

-Phosphorylase 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
(Co-stimulatory signal)
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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