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61 Cards in this Set

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Thymus-dependent lymphocytes?
1) aka T lymphocytes, Tcells
2) originate from bone marrow stem cells
3) migrate to mature in the thymus
2 lineages of T cells develop in the thymus?
1) a:B T cells
2) y:d T cells
a) thes lineages dev. In parallel from common precursor
Developing thymocytes?
1) Express other cell surface proteins
a) CD4 and CD8 gp.
(i) Which are essential for T cell response to cells presenting An.
Once T cells leave thymus >?
1) Secondary lymph tiss > return to lymph
the thymus?
1) Is a lymphoid organ in the upper anterior thorax (above heart)
a) Contains thymocytes embedded in the thymic stroma
thymocytes?
1) immature T cells
thymic stroma?
1) network of epithelial cells
thymocytes + thymic stroma = ?
1) outer close-packed cortex
2) inner, less dense, medulla
Cortex?
1) Epithelial cells arise form ectodermal cells
a) Consists of
(i) Immature thymphocytes
(ii) Branched cortical epithelial cells
(iii) A few macrophages
Medulla?
1) Epithelial cells derived from endodermal cells
a) Consists of
(i) Mature thymphocytes
(ii) Medullary epithelial cells
(iii) Dendritic cells
(iv) Macrophages.
One fnx of the macrophages in both cortex & medulla?
1) Is to remove the many thymocytes > fail to mature properly
Hassall’s corpuscles?
1) Char. Feature of medulla
2) Sites of cell destruction
thymic anlage?
1) ectodermal cells + endodermal cells
a) form rudimentary thymus
2) subsequently b/c colonized by cells from bone marrow
DiGeorge’s Syndrome?
1) Genetic disease
2) Thymus fails to develop,
a) T cells are absent,
b) Results in susceptibility to wide range of opportunistic infec.
3) Resembles SCID (severe combined immunodef disease.
thymus activity?
1) Most active – young
2) Atrophies w/ age
a) Degeneration complet by 30 years old.
impairment of T cell immunity is not effected by?
1) Reduced production of new T cells by thymus
2) Thymectomy (removal of thymus)
maturation of thymocytes into mature T cells occurs?
1) in distinct stages
a) marked by changes
Stages marked by distinct changes?
status of Tcell receptor genes
2) expression of the T cell receptor genes,
3) expression of the t cell receptor protein
4) production of the tcell surface fp essential for the receptors full fnx
a) such as CD4 & CD8 and CD3 complex
“double-negative” thymocytes?
1) immature thymocytes expressing neither CD4 nor CD8
as double neg. thymocytes mature?
1) 1st express the adhesion molecule CD44 then CD25
CD44 and CD25?
1) Component of the receptor for the cytokine interleukin-2 (IL-2).
After expression of CD 44 decreases ?
1) T cell receptor gene rearrangements commence.
T cells have two lineages?
1) expression of a:B receptor
2) expression of y:d receptor
commitment to lineage?
1) occurs as consequence of a race b/t the diff loci > productive rearrang.
What is the first major difference b/t Bcells and Tcells?
1) T cells stat to rearrange their B-, y-, and d-chain genes at about the same time.
2) B cells each type of Ig gene is rearranged in turn in a set order.
Lineage commitment to a:B or y:d t cells is consequence of ?
1) The order of successful gene rearangements
T cell progenitors express?
1) no t cell specific markers
2) they 1st express CD44 and CD25 cell surface gp.
after expression of CD44 and CD 25?
1) B-, y- and d- chain loci begin rearrangements.
if the y- and d- genes are rearranged productively before the B gene?
1) Appearance of y:d receptor on cell surface signals to Stop B-chain rearrang.
2) Cell commits to the y:d lineage
what is the more common outcome?
1) the B-chain gene rearrange productively before a fnx y:d receptor is made
If B-chain gene rearrange productively before fnx y:d receptor?
1) Pre-T-cell receptor
a) Signals to stop B-, y- and d- chain genes rearrang
b) And enter phase of proliferation
after proliferation ?
1) recom. Machinery is reactivated targeted to the a-chain locus (and the unproductive y-and d-chain genes.)
What if y- and d-chain genes are rearranged before a-chain genes?
1) Forms a y:d Tcell lineage.
2) This is minority
If a-chain gene occurs first ?
1) Leads to a:B cell receptor
a) Signals for a a:B T cell
Production of a T-cell receptor B-chain leads to cessation of ?
1) B-chain gne rearrangement
2) and to expression of CD4 & CD8
similarity between T cell rearrangements and Ig rearrangements?
1) rearrangements of a- & B- chain loci vs. Ig loci
a) Ig H-chain VS. Tcell B-chain
b) Ig L-chain VS. Tcell a-chain
c) RAG-1 and RAG-2 in both
d) Pre-Tcell receptor VS pre-Bcell receptor
Ig H-chain VS. Tcell B-chain?
1) contain V, D and J gene segments
2) rearranged first
Ig L-chain VS. Tcell a-chain?
1) No D segments
2) Rearranged second
RAG-1 and RAG-2 in both?
1) Gene rearrangement is preceded by small amounts of transcription from the gene segments to be recombined by expression of RAG genes
Pre-Tcell receptor VS pre-Bcell receptor?
1) Same function for both
a) Its appearance triggers the thymocyte to proliferate
(i) And to halt B-gene rearrangement.
the T cell receptor B-chain genes rearrange first in?
1) CD4- CD8- thymocytes (double negative)
a) That express CD25+ and CD44 low. On cell surface p.
what genes are rearranged first? And produces?
1) B-chain D to J
a) Then a V gene rearranges to DJ
2) B-chain protein
B chain protein?
1) Expressed w.in the cell and then
a) Appears in low levels on cell surface with surrogate a-chain (pTa) and CD3 chains ->Pre T cell preceptor
Expression of pre-T cell receptor signals?
1) stop B- rearrangement
2) cell proliferates
after cell proliferation?
1) CD4 and CD8 are expressed on cell surface
expression of CD4 and CD8 on cell surface signals?
1) a chain to rearrange
when a fnxal a chain is produced?
1) It pairs w/ the B-chain to form a a:B Tcell receptor.
2) Appears on surface with CD3 complex
when Tcell receptor appears w/ CD3 complex?
1) it is a double-positive thymocyte
double positive thymocyte?
1) expresses CD4, CD8 and the a:B Tcell receptor in assoc w/ CD3
2) it is ready to undergo selection
what is a major difference between Ig Hchain and Tcell B-chain?
1) Unproductively rearranged B-chain gene can be rescued by a second rearrangement
a) Because 2 sets of D(B)J(B) and C(B) gene segments are tandemly assoc w/ the V(B) gene segments.
what do Ig L-chains have in common with T cell a-chains?
1) They can undergo several successive gene rearrangements
a) Therefore has a greater chance of a successful rearrangement than the B locus
How does the a-chain have a greater chance of success?
1) The presence of many V(a) and over 50 J(a) gene segments,
a) Allows successive VJ(a) rearrangements to be tried
successful rearrangement of one copy of the a-chain gene and cell surface expression of a fnxal a:B receptor does NOT?
1) Prevent other copy of a-chain gene
2) Many T cells express 2 a-chains and have 2 diff. t cell receptors
a) Will be +/- selected later.
Cells expressing particular y:d receptors arise first in?
1) Embryonic development.
the 1st T cells to emerger during embryonic development carry?
1) y:d receptors
1st wave of y:d T cells ?
1) migrate specifically to the skin
a) called dendritic epidermal T cells (dETC)
2nd wave of y:d T cells?
1) Migrate to the epithelial layers of the reproductive tract.
each wave is characterized by ?
1) a distinctive y:d receptor that is carried by all the cells in a wave.
How are early y:d T cells analogous to the B-1 cells that emerge from the bone marrow before birth?
1) Timing of their emergence
2) Restricted use of particular gene segments
3) Lack of N nucleotides
4) Represent older, more primitive, and less specific components of the adaptive immune system
later on in embryonic development T cells?
1) Are produced continuously VS in waves
2) a:B cells now dominate (95%)
3) within y:d subpop.
later on in embryonic development T cells within y:d subpop.?
1) Receptors are more diverse
a) In number of alternative gene segments used
b) And in abundance of N-nucleotides additions
2) Found in peripheral lymphoid tissues VS solely in the epithelium of non.