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92 Cards in this Set
- Front
- Back
describe the two different TCR's expressed by T-cells?
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1. alpha/beta receptors
2. gamma/delta receptors |
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T cells that leave the thymus are restricted to those that express what?
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Self MCH (the MCH I and II that are expressed by that person)
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what is the first selection process through which the primary T-cell repertoire must undergo?
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positive selection for those that can bind self MCH I and II isoforms
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what is positive selection for T cells followed by?
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negative selection in which those T cells which bind too tightly to MCH are killed
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the majority of T cells have which receptor type?
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alpha/beta
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what are the immature T cells located in the thymus called?
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thymocytes
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where are the thymocytes located?
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in a network of epithelial cells called the thymic stroma
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the epithelial cells of the cortex are derived from?
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ectoderm
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the epithelial cells of the medulla are derived from?
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endoderm
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the epithelial cells from the cortex and medulla together form the?
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thymic anlage
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the progenitor cells from the bone marrow that infiltrate the thymic anlage give rise to what two cell types?
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1. thymocytes
2. dendritic cells |
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what other cell besides the progenitor cells comes to the thymus from the bone marrow?
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macrophages
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where are the macrophages primarily located in the thymus?
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the medulla
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As the thymocytes mature describe their direction of migration?
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from cortex to medulla
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what is the phrase that refers to the degeneration of the thymus after puberty?
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involution of the thymus
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What is the effect of removing the thymus in an adult?
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Nothing really happens becuase peripheral T cells are long lived and can self renew
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where do the progenitor cells from the bone marrow go to once the enter the thymus?
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in the subcapsular region of the outer cortex
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what signals the progenitor cells to proliferate in the thymus?
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interaction with the stromal cells (epithelial cell network)
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what do the resulting cells of progenitor proliferation display on their cell surface?
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CD2
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the cells expressing only CD2 and neither CD4 or CD8 are called?
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double negative thymocytes
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as the double negative thymocytes mature, describe the series of cell surface molecules they express?
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first CD44 (adhesion molecule) then CD25 (component of IL2 receptor)
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what determines whether a T cell will be a alpha/beta or gamma/delta?
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whichever can make a productive rearrangement first wins
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what is the major difference between the determination of the order of TCR loci rearrangement and BCR rearrangement?
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TCR gene loci all begin rearrangement at the same time while BCR gene loci proceed in a series
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what must happen for the a T cell to choose to have alpha/beta receptors?
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the beta-chain rearrangement must by productive before both gamma and delta chains
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which usually has a faster productive rearrangement, beta chains or the gamma/delta chains?
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the beta chains
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once a productive beta chain is assembled, how is a pre-T cell receptor made?
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beta chain is joined with a surrogate alpha chain
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the presence of the pre-T cell receptor on the T cell surface causes what to happen with chain rearrangement?
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it stops all chain rearrangment and the cells begin to proliferate
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after proliferation of T cells expressing pre-T cell receptors, what occurs?
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recombination machinery is expressed again and alpha, gamme, and delta chains all begin rearrangement
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what occurs if gamma/delta chains make a productive rearrangement before the alpha chain does?
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the T cell will express gamma/delta receptors instead of alpha/beta
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what does the rearrangement of the alpha chain locus mean for delta chain rearrangement?
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the delta chain gene loci is in the alpha chain so rearrangement of the alpha chain deletes delta gene loci from the chromosome
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how many thymocytes fail to make productive rearrangements?
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98%
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what happens to the thymocytes which have not made a productive rearrangement?
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they are all phagocytized by macrophages in the outer cortex
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which immunoglobulin gene loci is most similar to beta chain loci?
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the B cell heavy chain gene loci (VJD regions)
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which immunoglobulin gene loci is most similar to alpha chain loci?
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the B cell light chain gene loci (VJ regions)
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what are the recombination activation genes that are activated before alpha/beta gene loci rearrangement?
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RAG-1 and RAG-2 just like B cells
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describe all of the components of the pre-T cell receptor? (4)
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1. beta chain
2. surrogate alpha chain called the preTalpha 3. CD3 protiens 4. zeta chain |
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describe the two ways in which an unproductive rearrangement on the beta chain locus can be saved?
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1. a productive rearrangement on the beta chain locus on the second chromosome
2. a second, productive rearrangement on the same beta chain locus |
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how is it possible for a second rearrangement on the same beta chain locus to occur?
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two copies of the DJC regions exist in tandem with the V region thus if one is messed up it can be skipped an the other used
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what percent of T cells have a productive rearrangement of the beta chain?
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80%
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succesful rearrangement of the beta chain causes the expression of what two co-receptors on the cell surface?
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CD4 and CD8
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once the thymocyte expresses CD4 and CD8 it is called what?
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a double-positive thymocyte
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where are a double-positive thymocyte primarily found?
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inner cortex
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why does no rearrangement occur during cell proliferation initiated by pre-T cell receptor expression?
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RAG-1 and RAG-2 genes are shut down
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which has a greater chance of productive rearrangement, beta chains or alpha chains?
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alpha chains because like light chains of B cells, alpha chains can have several succesive gene rearrangments
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why can alpha chains undergo more gene rearrangements that beta chains?
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alpha chains have more V and J (over 50) gene segments which can be combined
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how is it possible for a T cell to express two different receptors?
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each T cell has two copies of alpha chain genes thus two productive rearrangements are possible and can be displayed simultaneously
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receptors do the first T cells in embryonic development display?
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gamma/delta receptors
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what is the first phase of T cell production?
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to make productive rearrangements leading to functioning TCR's regardless of antigenic specificity
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what is the second phase of T cell development?
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determination if a TCR, that has been produced in the first phase, has the ability to recognize self-MCH presenting self-peptides and MCH presenting pathogen-derived peptides
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how many of the TCR's made in phase one are able to recognize self-MCH?
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2%
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what is the name given to the process by which only a small population of T cells are able to bind self-MCH and thus survive?
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positive selection
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what happens to the T cells which fail positive selection?
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the die and are phagocytized by mcarophages in the thmyic cortex
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where does positive selection take place?
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thymic cortex
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what present the self-MCH with peptide from normal healthy cells to the double positive T lymphocytes?
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cortical epithelial cells
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what are the cortical epithelial cells derived from?
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ectoderm
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describe the time frame in which double positive T lymphocytes must bind self-MCH with self-peptides before apoptosis is initiated?
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3-4 days
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describe what a bone marrow donor and a bone marrow recipient must share in common for a bone marrow graft to be succesful
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the must share AT LEAST 1 HLA class I MCH and 1 HLA class II MCH
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other than selecting T cells which can interact the self-MCH, what else does positive selection do for T cells?
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selects whether they will express CD4 or CD8
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at the end of positive selection, what are thymocytes called?
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single-positive thymocytes
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which MCH class does CD4 react with?
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MCH II
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which MCH class doe CD8 react with?
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MCH I
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how does a CD4 or CD8 get to be the only co-receptor expressed?
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positive selection brings the thymocytes into contact with MCH class I or II. Whichever class it contacts determines the co-receptor displayed (CD4 or CD8)
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what is the name of the disorder in which either MCH class I or class II is not expressed?
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bare lymphocyte syndrome
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If a patient with bare lymphocyte syndrome is missing MCH class II what co-receptor will all the T cells express?
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CD8
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what is the process called by which T cells which bind too tightly to self-MCH and self-peptide are destroyed?
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negative selection
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which cells are most important in facilitating negative selection for T cells?
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bone marrow derived macrophages and dendritic cells
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how do the macrophages and dendritic cells help in negative selection?
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present thymic antigen to T cells and those T cells that bind too tightly are induced to undergo apoptosis
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the negative selection mediated in the thymus can only select for T cells not overly reactive to what?
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thymic self-peptides
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what process ensures that T cells reactive to self-peptides other than thymic self-peptides do not stay in circulation?
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a mechanism very similar to that of B cells in that T cells which bind soluble self-antigens become anergic
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what does HLA (as in HLA MCH II) stand for?
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human leukocyte antigen
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in the absence of antigen, how long to naive T cells circulate through the body?
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years
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describe the circulation pathway of both B cells and T cells?
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blood -> secondary lympoid tissue -> lymph -> blood
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what provokes the final phases of developmen and differentiation in naive T cells?
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binding of their specific antigen in T cell rich areas of lymphoid tissue
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once activated by antigen CD8 T cells become?
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cytotoxic T cells
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once activated by antigen CD4 T cells become?
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TH1 or TH2 cells
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what is the aproximate ratio of CD4 T cells to CD8 T cells in the peripheral circulation?
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2:1
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patients which aids see a drop in what kind of T cells in peripheral circulation?
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CD4 T cells
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additional MCH molecules expressed by an individual results in deletion of T cells equal to the ___ of the additional MCH molecules expressed?
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square
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what is the maximum of different MHC molecules that humans express?
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12 (3 per MHC Class = 6) (6 times 2 chromosomes = 12)
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how many stages are there for T cell development?
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4
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what is the first T cell developmental stage?
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proliferation and differentiation to double-positive CD3 thymocytes
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what is the second T cell developmental stage?
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positive selection
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what is the third T cell developmental stage?
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negative selection
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what is the fourth T cell developmental stage?
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entry to the circulation
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what are the thymocytes entering the first stage of T cell development called?
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double-negative thymocytes
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where are the thymocytes entering stage 1 located?
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subcapsulary zone
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what are the thymocytes entering the second stage of T cell development called?
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double-positive thymocytes
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where are the thymocytes entering stage 2 located?
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thymic cortex
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what are the thymocytes entering the third stage of T cell development called?
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double-positive thymocytes
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where are the thymocytes entering stage 2 located?
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throughout the cortex, but concentrated mostly at the cortico-medullary junction
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what are the thymocytes leaving the fourth stage of T cell development called?
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Mature single-positive CD4 or CD8 T cells
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where do cells which have passed stage 4 leave the thymus?
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blood venules
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