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Immunology Chapter 8 Kuby
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Immunology Chapter 8 Kuby
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Immunology Chapter 8 Kuby· CD4 CD8 (DP) thymocytes are small, nonproliferating, and dominate the thymic cortex
- ANS-o comprising more than 80% of cells in the thymus as a whole.
o are the first subpopulation of thymocytes that express a fully mature surface
TCR-αβ/CD3 complex
o are the primary targets of thymic selection
· Only 2% to 5% of DP thymocytes actually exit the thymus as mature T cells. - ANS-·
The vast majority of DP thymocytes (~98%) never meet the selection criteria and die by
apoptosis within the thymus
· Pre-TCR signaling results in commitment to the TCR-αβ lineage - ANS-o another burst
of proliferation, maturation to the DP stage of development, and initiation of TCR-α
rearrangement.
DN1 stage - ANS-· DN1 includes c-Kit (CD117)++, CD44++, and CD25-
a. still multipotent, they receive Notch signals immediately on entering the thymic
environment and begin to restrict themselves to the T-cell lineage.
They travel to the cortex, where they proliferate and gain expression of CD25
DN2 stage - ANS-DN2 includes c-Kit (CD117)++, CD44+, and CD25+
a. the genes for the TCR γ, δ, and β chains rearrange (Takes place in the subcapsular
cortex)
b. The TCR α-chain locus does not yet rearrange.
c. At the late DN2 stage, T-cell precursors fully commit to the T-cell lineage and reduce
expression of both c-Kit and CD44.
DN3 stage - ANS-a. continue to rearrange their TCR γ, TCR δ, and TCR β chains and
make the first major decision in T-cell development: whether to join the TCR-γδ or
TCR-αβ T-cell lineage.
, Those DN3 T cells that successfully rearrange their β chain typically commit to the
TCR-αβ T-cell lineage.
b. They lose expression of CD25, halt proliferation
DN4 stage - ANS-a. matures directly into CD4 CD8 DP thymocytes.
b. a-chain rearrangement begins at the DN4 stage
c. Allelic exclusion of beta chain locus+
Double negative (DN) T cell - ANS-a. The earliest T cells lack detectable CD4 and CD8
and are therefore referred to as double negative (DN) cells.
How are DN T cell stages categorized? - ANS-DN T cells can be divided into four
subsets based on the presence or absence of other cell surface molecules (c-kit CD117,
the receptor for stem cell growth factor, CD44, an adhesion molecule, and CD25, the a
chain of the interleukin (IL)-2 receptor):
How are TCR genes generated? - ANS-· TCR genes are generated by shuffling
(rearranging) V and J (and sometimes D) segments.
How are TCR-γδ cells unique? - ANS-· Most do not go through the DP stage of
thymocyte development and, instead, leave the thymus as mature DN (CD4 CD8 ) T
cells
emerge from the thymus with the ability to secrete cytokines
o a capacity gained by most TCR-αβ cells only after they encounter antigen in
secondary lymphoid tissues.
expresses receptors that are not as diverse as TCR-αβ T cells.
· Many take up long-term residence in mucosal tissues and skin and join innate immune
cells in providing a first line of attack against invading microbes, as well as the response
to cellular stress.
· TCRγδ are more common in fetal development
o Fetal developmental environment may provide different signal cues
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