Chapter 7: Development Of T Lymphocytes Flashcards

1
Q

T cell precursor migrate from the…

A
  • bone marrow to the thymus to mature
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2
Q

Mature T cells leave…

A
  • the thymus in the blood, from where they enter secondary lymphod tissues and then return to the blood and the lymph
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3
Q

The cortex consists of…

A
  • immature thymocytes
  • branched cortical epithelial cells
  • few macrophages
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4
Q

The medulla consists of…

A
  • mature thymocytes
  • medullary epithelial cells
  • dendritic cells
  • macrophages
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5
Q

One functions of the macrophages in both the cortex and medulla is to…

A
  • remove the thymocytes that fail to mature properly
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6
Q

The human thymus is fully developed before birth and as a person ages…

A
  • the thymus begins to degenerate and replace with fatty tissue
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7
Q

Thymocytes commit to the T-cell lineage before rearranging their T-cell receptor genes. When entering the thymus they become…

A
  • CD34+
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8
Q

After a week of interaction with the ____________ ______________ cell, these stem cells differentiate and lose their stem cell markers.

A
  • thymus stromal
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9
Q

Commitment to the T-cell lineage involves changes in ______ _____________ and in cell-surface markers

A
  • gene expression
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10
Q

Cells are called ________ _________ thermocytes do not express CD4 nor CD8

A
  • double negative
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11
Q

IL-7 first critical cytokine important in…

A
  • development of T cells
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12
Q

What is Notch 1?

A
  • major regulator of T cell development

- helps in transcription of gene necessary for T cell development

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13
Q

T-cell development is driven by the receptor…

A
  • Notch 1
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14
Q

Activity of Notch 1

A
  • Notch 1 on the thermocyte binds to its ligand on thymic epithelial
  • this induces a protease to cleave the intracellular domain from the PM
  • the soluble intracellular domain is translocated to the nucleus, where is turns on the expression of genes essential for T-cell development
  • removal of repressive transcription factors and recruiting co-activating transcription factors
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15
Q

Two lineages of T cells arise from a…

A
  • common thymocyte progenitor
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16
Q

ALPHA:BETA and GAMMA:DELTA develop from a…

A
  • common double-negative T-cells progenitor
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17
Q

T-cell precursor that enter the thymus express the hematopoietic stem cell marker ______ but none of the characteristic markers of mature T cells

A
  • CD34
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18
Q

Proliferation of these common progenitors followed by ______________ of the delta-, gamma- and beta-chain genes, which leads to early commitment of some cells to the gamma:delta T-cell linage, whereas others rearrange the _________ chain gene first and temporarily halt _____ ________ at this point.

A
  • rearrangement
  • beta
  • gene rearrangement
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19
Q

Once a complete gamma:delta receptor is created the T cells…

A
  • leave the thymus and travel to other tissues via the blood
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20
Q

The beta-chain-positive cells in the thymus, rearrangement of the alpha-, gamma-, and delta chain genes resumes productive alpha-chain gene rearrangements in these cells producing a ___________-___________ __________ __________ alpha:beta cells

A
  • double-positive
  • CD4
  • CD8
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21
Q

Minority of double-positive thymocytes give rise additional gamma:delta T-cells. This ends…

A
  • the early stage of alpha:beta T-cell development
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22
Q

Alpha:Beta and Gamma:Delta T-cells develop from a common ___________-____________ T-cell ________________.

A
  • double-negative

- progenitor

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23
Q

Gene rearrangement…

A
  • in double-negative thymocytes leads to assembly of either a gamma:delta receptor or a pre-T-cell receptor
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24
Q

T cells can can also make productive and nonproductive gene rearrangent

A
  • like immunoglobulins
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25
Q

There are _____ chromosomes for each of the _____ locus

A
  • two

- two

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26
Q

Beta and Delta chains are like _______________ heavy chain and contain _______ segments, where as alpha and gamma are like the immunoglobulin LC containing ________ segments.

A
  • immunoglobulin
  • VDJ
  • VJ
27
Q

For beta and delta:

A
  • first rearrangement joins the DJ

- second rearrangement joins the V to the DJ

28
Q

For alpha and gamma…

A
  • single rearrangement joins V to J
29
Q

Alpha (alpha) chain gene rearrangement occurs…

A
  • last
30
Q

By the way, alpha chain which is like an Ig LC has surrogate (pT-alpha) to test the productive beta chain protein in the…

A
  • Endoplasmic Reticulum
31
Q

If the beta chain bind pT-alpha, the heterodimer assembles with the CD3 complex. This assembly is called the…

A
  • pre-T-cell receptor
32
Q

Thermocytes can make _________ attempts to rearrange a beta-chain gene

A
  • four
33
Q

What is the successive rate of producing a beta chain gene rearrangement?

A
  • 80%
34
Q

Non-productive gene rearrangement can be rescued __________ in the same loci, thus up to 4 chances. There are only 2 chromosomes.

A
  • once
35
Q

Rearrangement of the alpha-chain gene occurs in pre-T cells. No pre-T cell, ____ ______________ of the alpha chain gene

A
  • No rearrangement
36
Q

Once a successfull B chain is made (gotta get checked with the surrogate alpha chain, pT-alpha), then the pre-T cell stops the RAG1 and RAG2

A
  • no further rearrangement goes on with beta

- proliferation then occurs (takes place)

37
Q

The first two molecules made are double positive cells are…

A
  • CD4 and CD8
38
Q

Alpha chain gene rearrangement can start when?

A
  • when the the first CD4 and/or CD8 molecules are made
39
Q

What happens to delta chain gene?

A
  • gets deleted in the process cause within alpha chain DNA
40
Q

Rescue of unproductive rearrangements of the beta-chain locus only if…

A
  • that rearrangement involves D and J gene segments associated with the C-beta-1 gene segment
  • then the second rearrangement is then possible where the V-beta gene segment rearranges to a DJ segment associated w/ the C-beta-2 gene segment, deleting C-beta-1 and the unproductively rearranged gene segments
41
Q

Successive gene rearrangements allow the replacement of one T-cell receptor alpha chain by another.

A
  • multiplicity of V and J gene segments allow successive rearrangement events to jump over unproductively rearranged VJ segments, deleting the intervening gene segments
  • this process continues until either a productive rearrangement occurs or the supply of V and J gene segments is exhausted, where the cell will die
42
Q

Stages in T-cell development are marked by changes in _____________ expression

A
  • gene
43
Q

Once a developing thymocyte expresses an alpha:beta receptor and CD4 and CD8 on its surface, it undergoes two types of selection:

A
  • positive and negative
44
Q

Both types of selection involve testing the receptor’s interaction with the complexes of self peptides bound by self-MHC molecules on the surfaces of thymic cells. We focus on the _______:_________

A
  • alpha:beta
45
Q

T cells that recognize ______-______ are positively selected in the _____________ (cortex)

A
  • self-MHC

- thymus

46
Q

Positive selection

A
  • process whereby a small subpopulation (2%) is selected and signaled to mature further
  • the vast majority of double positive (CD4, CD8) T cells (98%) die by apoptosis in the thymic cortex
47
Q

Mechanism of positive selection

A
  • T-cells w/ a T-cell receptor (TCR) that binds to a self-MHC class 1 molecule on thymic cortical epithelial cells, macrophages, and other cells in the thymus are signaled to survive and proceed to negative selection
  • T-cells w/ a TCR that binds to no self-MHC class 1 molecules are signaled to die (APOPTOSIS)
  • same is true for self-MHC class 2
48
Q

Continuing alpha-chain gene rearrangement increases the chance for ________________ selection

A
  • positive
  • first alpha chain gene rearrangement that a pre-T cell makes is productive and leads to the assembly of an alpha:beta TCR that interacts w/ a self self-MHC molecule positive selection will occur within a few hours
49
Q

The T cells is then signaled to turn off the RAG genes and ____________________ machinery.

A
  • recombination

- cell then enters a phase of proliferation

50
Q

If the TCR does not bind a self-MHC molecule, _____________ of the alpha chain continues until 3-4 days to improve its chances of having a binding site that bind MHC molecules.

A
  • rearrangement

- there is no allelic exclusion in alpha chain rearrangement, unlike the beta chain

51
Q

Positive selection determines expression of either the _______ or the ________ co-receptor

A
  • CD4

- CD8

52
Q

Double positive becomes a…

A
  • single-positive thymocyte
53
Q

During positive selection, the double positive will interact through its ______:______ receptor with a particular peptide: ________ complex

A
  • alpha:beta
  • MHC
  • when interacting MHC molecule is class 1, CD8 molecules are recruited into the interaction (CD4 is excluded)
  • when interacting MHC molecule is class 2, CD4 molecules are recruited and CD8 are excluded
54
Q

Negative selection of the T cell repertoire can be also called…

A
  • central tolerance
55
Q

T cells specific for self antigens are…

A
  • removed in the thymus by negative selection
56
Q

Negative selection deletes by ______________ T cells whose antigen receptors _________ __________ __________ to the complexes of self peptides and self MHC molecules presented by cells in the thymus.

A
  • apoptosis

- bind too strongly

57
Q

T cells are autoreactive and if allowed to enter the peripheral circulation they could cause damage and autoimmune disease describes…

A
  • negative selection
58
Q

Positive selection is mediated exclusively by epithelial cells in the cortex of the thymus, negative selection can be mediated by several cell types which are…

A
  • dendritic
  • macrophages
  • thymocytes
59
Q

Where do these self antigen come from in order to participate in negative selection?

A
  • tissue-specific proteins are expressed in the thymus
60
Q

Autoimmune Regulator (AIRE)

A
  • caused several hundred of these self antigen to be expressed by epithelial cells in the medulla of the thymus
61
Q

Peripheral Tolerance

A
  • like autoreactive B-cells that barely graduate the bone marrow, T cells undergo anergy
62
Q

Autoreactive T-cells are suppressed by _________ T regulatory cells

A
  • CD4
  • regulatory CD4 T cells comprise a distinct lineage of CD4 T cells
  • suppression of an autoreactive CD4 T cells by a regulatory T cell is dependent on the interaction of both T cells with the same APC
63
Q

Treg cells are specific for…

A
  • self antigens
64
Q

T reg cells have ________ on its surface, unlike other CD4 T cells

A
  • CD25