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