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Imunology > T Lymohocytes > Flashcards

T Lymohocytes Flashcards

1
Q

What happens when immature T cells leave bone marrow?

A

migrate to thymus for development

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2
Q

What is the goal of development?

A

mature T cells that leave thymus have diverse receptor specificity, are tolerant to self antigen, and recognize self MHC

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3
Q

What are the 2 phases of T lymphocyte development?

A
  • early phase
  • second phase
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4
Q

What happens in the early phase?

A
  • commitment to T-cell lineage
  • gene recombination
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5
Q

What happens in the second phase?

A
  • selection for cells with receptors that recognize self MHC
  • selection against cells with receptors that recognize self antigen
  • commitment to CD4 or CD8 lineage
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6
Q

How do immature T cells know how to develop?

A

-move through different microenvironments which provide signals for the stages of development

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7
Q

What do the signals for the stages of development come from?

A

binding receptors on cells and from cytokines

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8
Q

Where do immature T cells enter the thymus?

A

at corticomedullary junction which is between the medulla and cortex

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9
Q

How do immature T cells travel through thymus?

A

travel through cortex, finish development in medulla, before leaving thymus as mature T cells

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10
Q

How long does T cell development take?

A

1-3 weeks

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11
Q

T cell precursors that enter the thymus are…

A

double negative

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12
Q

What does being double negative mean?

A

do not express CD4 or CD8

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13
Q

What are the stages of the early phase?

A
  • DN1 stage
  • DN2 stage
  • DN3 stage
  • DN4 stage
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14
Q

What is the DN1 stage characterized by?

A

cells that have CD44

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15
Q

What happens during the DN1 stage?

A
  • cells proliferate
  • begin to express CD25
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16
Q

What is the DN2 stage characterized by?

A

cells with CD25 and CD44

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17
Q

What happens during the DN2 stage?

A
  • recombination of TCR beta, gama, delta chains
  • cells fully commit to T cell lineage
  • lose expression of CD44
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18
Q

What is the DN3 stage characterized by?

A

cells with CD25

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19
Q

What happens in the DN3 stage?

A
  • Beta selection
  • lose expression of CD25
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20
Q

What is beta selection in the DN3 stage?

A
  • cells that have successfully undergone gene recombination of beta chain have become alpha beta T cells
  • remaining cells become gamma delta T cells
  • cells that are selected for express pre-alpha chain
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21
Q

What is the DN4 stage characterized by?

A

cells with no CD44 or CD25

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22
Q

What happens in the DN4 stage?

A
  • alpha chain recombination of TCR
  • cells gain expression of CD4 and CD8 (become double positives)
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23
Q

What are the stages of the second phase of development?

A
  • positive selection stage
  • negative selection stage
  • lineage commitment stage
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24
Q

What happens in the positive selection stage?

A
  • select for cells with TCRs that bind self MHC
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25
Q

What is it called when you select for cells that bind self MHC?

A

MHC restriciton

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26
Q

What happens in the negative selection stage?

A

select against cells that strongly bind to self-antigen

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27
Q

What does selecting against cells that strongly bind to self-antigen?

A

establishes self-tolerance

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28
Q

What happens during the lineage commitment stage?

A

silencing of either CD4 or CD8 gene to have either CD4+ or CD8+

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29
Q

What happens at end of second phase of T cell development?

A

mature T cells leave thymus and enter bloodstream

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30
Q

What do regulatory T cells (Tregs) express?

A

CD4, CD25, FoxP3

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31
Q

Where do regulatory T cells develop and what from?

A

in thymus from autoreactive T cell precursors

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32
Q

How do Tregs dampen immune response?

A
  • compete for cytokines with other T cells
  • secrete inhibitory cytokines
  • inhibit professional APCs
  • kill other immune cells
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33
Q

What is it called when Tregs compete for cytokines with other T cells?

A

cytokine deprivation

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34
Q

How do Tregs kill other immune cells?

A

using perforin and granzyme

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35
Q

Where does T cell activation occur?

A

lymph nodes/ secondary lymphoid tissues

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36
Q

What is required for T cell activation?

A
  • TCR complex
  • adhesion molecules
  • co-stimulatory receptors
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37
Q

What does TCR bind to? (TCR complex)

A

MHC/antigen

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38
Q

What does CD4 or CD8 on TCR complex bind to?

A

-CD4 binds MHC-II
_ CD8 binds MHC-1

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39
Q

What does CD3 on TCR complex bind to?

A

doesn’t bind to anything

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40
Q

What is the purpose of CD3 on TCR complex?

A

allows for transduction of signals in cell

41
Q

What do adhesion molecules do?

A

adhere the cell to APCsW

42
Q

What adhesion molecules do T cells express?

43
Q

What does LFA-1 bind?

A

binds to ICAM-1 and ICAM-2 on APCs

44
Q

What does CD2 bind?

A

binds to LFA-3 on APCs

45
Q

What are co-stimulatory receptors required for?

A

to complete activation signaling

46
Q

What are the co-stimulatory receptors?

A
  • CD28
  • CTLA-4
47
Q

What does CD28 bind to? What does this do?

A
  • binds to CD80 or CD86 on APCs
  • activation
48
Q

What does CTLA-4 bind to? What does this do?

A
  • CD80 or CD86
  • inhibition
49
Q

What 3 signals does T cell activation require?

A
  • TCR complex binds to MHC-antigen
  • CD28 binds to CD80 or CD86
  • IL-2 secreted by T cell, binds to IL-2 receptors on that same T-cell
50
Q

What do the 3 signals that T cell activation requires stimulate?

A

proliferation of the T cell

51
Q

What is proliferation?

A
  • activated T cells divide 2-3 times a day or 4-5 days
  • during this time, cytokines stimulate T-cells to differentiate into specialized effector cells and small subset of memory cells
52
Q

What are polarizing cytokines?

A

cytokines secreted by immune cells due to PRR signaling

53
Q

What do polarizing cytokines do?

A

act on proliferating T cells to cause differentiation

54
Q

What does each subset of effector T helper cells have?

A

distinct cytokines (polarizing cytokines) that induce expression of a master gene regulator

55
Q

What does the master gene regulator do?

A

regulates gene expression for cytokines (aka effector cytokines)

56
Q

When are effector cytokines produced?

A

when the TH cells are fully differentiated

57
Q

What are the different types of T cell differentiation?

A
  • TH 1
  • TH 2
  • TH 17
  • TFH
  • Induced TReg
58
Q

What polarizing cytokines are present in TH 1 differentiation?

A
  • IL-12
  • IFN - gamma
  • IL - 18
59
Q

What does TH1 differentiation result in?

A

expression of master gene regulator T-Bet

60
Q

What effector cytokine does TH1 cell secrete?

A

INF- gamma, TNF

61
Q

What polarizing cytokine is present in TH2 differentiation?

62
Q

What does TH2 differentiation result in?

A

expression of master gene EATA3

63
Q

What effector cytokines do TH2 cells secrete?

A
  • IL-4
  • IL-5
  • I-13
64
Q

What polarizing cytokines are present in TH17 differentiation?

A
  • IL-6
  • IL-23
  • TGF - beta
65
Q

What does TH17 differentiation result in?

A

expression of master gene regulator RORY

66
Q

What effector cytokines do TH17 cells secrete?

A
  • IL-17 A
  • IL- 17 F
  • IL - 22
67
Q

What polarizing cytokines are present in TFH differentiation?

A
  • IL-6
  • IL - 21
68
Q

What does TFH differentiation result in?

A

expression of master gene regulator BC-1-6

69
Q

What effector cells do TFH cells secrete?

A

IL-4 and I-21

70
Q

What polarizing cytokines are present in Induced TReg differentiation?

A

IL-2 and TGF- beta

71
Q

What does induced Treg differentiation result in?

A

expression of master gene regulator FoxB3

72
Q

What effector cytokines do Induced Tregs secrete?

A

IL-10, TGF-beta

73
Q

What do cytotoxic T cells’s cell mediated response?

A

CD8 T cell response

74
Q

What does the generation of effector cells require?

A
  • interaction with MHC-1 antigen complex on APC
  • help TH1 CD4+ effector cells
75
Q

What is APC liscensing?

A

TH1 cells interact with professional APCs to allow for cross presentation

76
Q

What is cross presentation?

A

expressing MHCII and MHCI

77
Q

What are the licensing steps?

A
  • TCR complex on TH1 cells binds to MHC-II antigen on professional APC
  • CD40L on TH1 cell binds to CD40 on professional APCs
  • results in cross presentation of MHC-I and MHC-II
78
Q

How does CD8+ T cell activation occur?

A
  • TCR binds to MHC-I antigen on licensed professional APC (CD* binds to MHC-I)
  • CD28 on T cell binds to CD80 or CD86 on licensed APC
  • IL-2 secreted by T cell binds to IL 2 receptor on same T cell
  • results in proliferation and differentiation into cytotoxic T cells
79
Q

Can licensing and CD8 T cell activation occur at the same time?

80
Q

What are the types of effector cytotoxic T cells?

81
Q

What does Tc1 secrete?

82
Q

What does Tc1 do?

A

kill infected cells via perforin and granzyme as well as Fas-FasL signaling

83
Q

What does Tc2 secrete?

A

IL-4 and IL-5

84
Q

What does Tc2 do?

A

kill infected cells using only perforin granzyme

85
Q

What is the Kiss of Death?

A

cytotoxic T cells bind to infected cells

86
Q

How does the kiss of death occur?

A
  • T cell receptor binds to MHC-1 antigen on infected cells
  • adhesion molecules bind surrounding TCR
  • contents of CTL (centrosomes and granules) polarize to site of interaction
  • granules of CTL exocytose and contents are released into synpase between CTL and infected cell
87
Q

What ways does CTL kill?

A
  • granzyme/perforin
  • FasL
88
Q

How does CTL kill using perforin and granzyme?

A
  • TCR engagement results in an increase in Ca^2+ in CTL
  • this results in exocytosis of perforin and granzyme
  • perforin embeds in infected cell membrane and polymerizes to form holes in membrane
  • granzyme enters cell and initiates apoptosis
89
Q

How does CTL kill using FasL?

A
  • FasL on CTL binds to Fas on infected cell
  • signaling through Fas initiates apoptosis of infected cell
90
Q

What are the types of memory T cells?

A
  • Stem cell memory T cell (Tscm)
  • Central memory T cell (Tcm)
  • effector memory T cell (Tem)
  • resident memory T cells (Trm)
91
Q

Where are stem cell memory T cells found?

A

in secondary lymphoid tissues

92
Q

What do stem cell memory T cells have the potential for?

A

becoming other types of memory T cells

93
Q

Where do central memory T cells reside and travel between?

A

secondary lymphoid tissue

94
Q

What happens when central memory T cells are activated?

A

can quickly develop into any type of effector cell based on cytokines that are present

95
Q

What do effector memory T cells travel between?

A

travel between tertiary and lymphoid tissues

96
Q

What do effector memory T cells exhibit?

A

exhibit effector function because they have undergone differentiation

97
Q

Where do resident memory T cells reside?

A

in tertiary lymphoid tissueW

98
Q

When are resident memory T cells ready to respond?

A

upon secondary infection

Imunology (12 decks)

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