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Immunology test III > Lecture 14 - Differentiation and Functions of CD8+ T cells > Flashcards

Lecture 14 - Differentiation and Functions of CD8+ T cells Flashcards

1
Q

All T lymphocytes have what marker?

A

CD3 (TCR)

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2
Q

All T cells are derived from what?

A

Thymus

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3
Q

Helper T cells have what marker?

A

CD4

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4
Q

CTLs have what marker?

A

CD8

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5
Q

What is the typical percentage of Th and CTLs in blood?

A

Th - 66%

CTLs - 33%

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6
Q

T cells make up what percentage of all lymphocytes in the blood?

A

70%

B cells comprise the remaining 30%

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7
Q

CD8+ T cells are activated where and by what cells?

A

In the LN and by dendritic cells loaded with Ags exactly as CD4+ T cells are.

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8
Q

What do CTLs recognize?

A

Class I MHC-associated peptides

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9
Q

Once CTLs are activated, what follows?

A

They proliferate and leave the LN

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10
Q

CD8+ T cells are activated by mechanisms that involves what?

A

Cross-presentation of antigens to CD8+ T cells

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11
Q

Cells infected with intracellular microbes, such as viruses, are ingested by what?

A

DCs

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12
Q

CD8+ T cells are class ___ MHC- restricted

A

I

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13
Q

Naive CD8+ T cells recognize what?

A

Peptide Ags presented by DCs in the lymph nodes

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14
Q

CD*+ T cells are stimulated to do what?

A

Proliferate and differentiate into CTLs (and memory cells)

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15
Q

Once CTLs are activated the enter what?

A

The circulation and migrate to the site of Ag

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16
Q

CD8+ CTLs recognize the Ag at the site of Ag in the tissues and respond how?

A

By killing the target cells where the Ag is produced

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17
Q

The naive CD8+ T cells, like all naive T cells, are activated by what?

A

Ags presented by DCs

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18
Q

Ags recognized by CD8+ T cells may be from what?

A

Viruses or tumors derived from a variety of cell types

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19
Q

The process of cross-presentation is critically important for what?

A

Ag presentation by professional APCs within class I MHC

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20
Q

Exogenous Ags derived from ingested infected cells, tumor cells, or their proteins are transferred into the cytosol for processing, loading and presentation on what?

A

Class I MHC molecules

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21
Q

What is the first signal for the activation of naive CD8+ cell?

A

Recognition of Ags

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22
Q

What is the second signal for the proliferation and differentiation of CD8+ cells into effector CTLs?

A

CD28-CD80 costimulation

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23
Q

Activated CTLs contain numerous amounts of what?

A

Granules called lysosomes

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24
Q

What do granules contain?

A

Perforin and granzymes used by the cells to kill other cells

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25
Q

What do activated CTLs secrete?

A

Cytokines, mostly IFN-γ, that potently activate macrophages

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26
Q

Similar to the activation of Th1 cells, the molecular events in CTL differentiation involve what TF?

A

T-bet

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27
Q

What does T-bet regulate?

A

Transcription of genes encoding perforin, granzymes, and IFN-γ

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28
Q

What provides signal 3 in the form of cytokines which enhance activation of CTLs?

A

CD4+ helper T cells

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29
Q

Of particular importance, CD4+ helper T cells are required for CD8+ T cells responses when?

A

Relatively weak innate immune reactions are evoked by laten viral infections, organ transplants, and tumors

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30
Q

Evidence suggests that CD4+ helper T cells are more important for the generation of what ?

A

CD8+ memory T cells than for the differentiation of naive CD8+ T cells into effector CTLs

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31
Q

Licensing of the APC occurs when?

A

The CD4+ T cell recognizes Ag presented by an MHC class II+ APC

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32
Q

Licensing of APC delivers activating signals through what?

A

CD80/CD86 and CD40

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33
Q

Activated CD4+ Th cells express what?

A

CD40L

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34
Q

What does CD40L bind to?

A

To CD40 on Ag-loaded DCs

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35
Q

What does the CD40-CD40L interaction upregulates?

A

Expression of CD80/CD86 on professional APCs which makes them more efficient at sitmulating the differentiation of CD8+ T cells

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36
Q

True or False?

IT is required for CD4+ and CD8+ T cells should come in contact with APC at the same time?

A

FALSE

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37
Q

What role does IL-2 play in the activation of CD8+ T cells into CTLs and memory cells?

A

It promotes the proliferation and differentiation

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38
Q

What may CD8+ T cells express at high levels after activation?

A

α subunit of IL-2R

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39
Q

The IL-2 shares a common receptor component (the γ chain) with what?

A

IL-15 and IL-21

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40
Q

IL-12 and Type I IFNs stimulate what?

A

The differentiation of naive CD8+ T cells into effector CTLs

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41
Q

Naive CD8 T cells proliferate in response to what? What is needed for survival and development for optinal effector functions?

A

TCR and CD28 signals, but require IL-12 or type I IFN for survival and development of optinal effector functions

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42
Q

IL-15 may be produced by what cells?

A

DCs and tissue Mo

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43
Q

What is IL-15 important for?

A

The survival of memory CD8+ T cells

44
Q

Mice laking IL-15 showed what?

A

Significant loss of memory CD8 T cells

45
Q

IL-21 produced by activated CD4 T cells play a role in what?

A

Induction of CD8 T cell memory and the prevention of CD8 T cell exhaustion

46
Q

What was IL-2 originally known as?

A

T cell growth factor due to its effects on T lymphocyte activation and proliferation

47
Q

What is a major feature of IL-2?

A

Autocrine loop through which it operates

*15 kDa polypeptide

48
Q

Local release of IL-2 can lead to what?

A

Activation of T cells which results in massive upregulation of production of both the cytokine and its receptors
And the activation of nearby CD8 T cells in a paracrine fashion

49
Q

IL-2 shares a common receptor component with what other cytokines?

A

IL-4, 7, 9, 15, 21

50
Q

What is a key cytokine produced by activated DCs and Mo?

51
Q

IL-12 has a profound effect on what?

A

Inducing naive CD4 T cells to differentiate into Th1 effector cells

52
Q

The balance of IL-12 and IL-4 during naive CD4 T cell activation thus determines what?

A

Whether these cells become Th1 or Th2

53
Q

IL-12 promotes the production of what cytokines?

A

Pro-inflammatory cytokines IFN-γ and TNF-β by CD4 and CD8 T cells

54
Q

IL-12-stimulated CD8 T cells are more effective in what?

What do they maintain?

A

Controlling tumor

Maintain high numbers and function as compared to type I IFNs-stimulated cells

55
Q

IL-12 assists in prevention of what?

A

CD8 T cell exhaustion

56
Q

IL-12 also activates ___ cells

57
Q

The primary source of IL-15 is what?

A

Activated tissue Mo and Mature DCs

58
Q

IL-15 has similar biologic properties with what cytokine?

A

IL-2, which is consistent with their shared receptor (R) signaling componets

59
Q

IL-15 was first identified as what?

A

T-cell growth factor through its ability to promote the proliferation of CTL cells

60
Q

Exogenous IL-15 favors what?

A

Human Th1 T-cell differentiation in vitro

61
Q

IL-15 acts as a potent _________ for T cells isolated from human blood.

A

Chemoattractant

62
Q

IL-15 stimulates proliferation of what?

A

memory CD4 and CD8 and naive CD8 T cells

63
Q

IL-15 has been shown to costimulate what?

A

Innate immune IFN-γ production

64
Q

IFN-γ is a homodimer composed of subunits of approximately ___ kDa

65
Q

IFN-γ is released by what cells?

A

Th1, CTLs, activated NK cells

66
Q

INF-γ is a potent activator of what?

A

Mo

inducing an increase in metabolic, phagocytic and killing activity

67
Q

INF-γ has the ability to increase expression of what?

A 
MHC class I on a range of cell types 
MHC class II on professional APCs
68
Q

IFN-γ may be an important component of antiviral protection, since it does what?

A

Up-regulates Ag presentation of viral targets by infected cells

69
Q

IFN-γ favors the development of what cells?

A

Th1 cells and B cell differentiation biasing the production of immunoglobulin in favor of IgG and away from IgE

70
Q

In acute infections, CD8 T cells differentiate into what?

A

CTLs that eliminate the infected cells

71
Q

Activated CTLs secrete what?

A

Pro-inflammatory TNF-β, IFN-γ, and cytotoxic perforin and granzymes

72
Q

After viral clearance, the CD8 T cells undergo what?

A

Extensive contraction phase, mediated by apoptosis

73
Q

In some chronic viral infections, the responses of CD8 T cells may be initiated but gradually extinguished. This phenomenon is called what?

A

Exhuastion

74
Q

Exhaustion is an active ______ of immune responses first described in a chronic viral infection

A

suppression

75
Q

Exhausted CD8 T cells show reduced production of what? What has its expression increased?

A

IFN-γ - reduced

PD-1 inhibitory receptor - increased

76
Q

Inhibitory signals from PD-1 block what?

A

The activation of CTLs

77
Q

PD-1-mediated T cell exhaustion may contribute to what?

A

Chronicity of HIV and hep C virus

78
Q

Anti-PD-1 Abs are effective in what?

A

immuno-therapy of tumors

79
Q

CTL-mediated cytotoxicity involves what?

A

Specific TCR-dependent recognition and induction of apoptosis in target cells

80
Q

Interaction of TCR with Class I MHC brings CTL and the target cell in close contact which results in what?

A

The formation of the immunologic synapse

81
Q

The immunologic synapse ensure what?

A

That normal bystander cells are not injured by CTLs reacting against infected cells

82
Q

What is secreted from CTLs into the synapse that performs the killing and cannot diffuse to other nearby cells?

A

Perforin and granzymes

83
Q

True or False

CTLs themselves are not injured during the killing of targets

84
Q

How are target cells killed involving perforin and granzymes?

A

Complex of perforin and granzymes are released form the CTL by granule exocytosis and enter target cells
The granzymes are delievered into the cytoplasm of the target cells by a perforin-dependent mechanism, and they induce apoptosis

85
Q

How are target cells killed by FasL?

A

FasL is exdpressed on activated CTLs, engages Fas on the surface of target cells, and induces apoptosis

86
Q

Granzymes A, B and C are what?

A

Serine proteases

87
Q

Which Granzyme is the only one shown to be required for CTL cytoctoxicity in vivo?

88
Q

Describe perforin?

A

A membrane-perturbing molecule that is homologous to the C9 complement protein

89
Q

The granules also contain a sulfated proteoglycan serglycin which serves to do what?

A

Assemble a complex containing granzymes and perforin

90
Q

Perforin insertion into target cell membrane elicits what?

A

Membrane repair process, which leads to internalization of both the perforin and granzymes into endosomes

91
Q

When in target cell, what does granzyme B do?

A

Activates caspase-3 that triggers apoptosis

92
Q

Binding of FasL to Fas recruits what?

A

procaspase-8 .

93
Q

What converts the procaspase-8 into caspase-8?

A

FADD adaptor

94
Q

In type-I cells such as thymocytes, caspase-8 can directly cleave what?

95
Q

In type-II cells such as virus-infected hepatocytes, caspase-8 cleaved what? What results from this?

A

Cleaves Bid

The truncated Bid stimulates the release of cytochrome c from mitochondria

96
Q

Macrophage activation by Th1 cells is an important immune mechanisms for eliminating what?

A

Bacteria which can resist lysosomal degradation

97
Q

Cytochrome c, togehter with apoptotic peptidase activating factor 1 (Apaf-1) and ATP goes on to activate what?

A

Caspase -9

98
Q

What does caspase - 9 activate?

A

Caspase -3

99
Q

What is one of the substrates of caspase-3?

A

ICAD (inhibitor of caspase-activated DNase)

100
Q

Th1 cells make Il-3 and GM-CSF, which does what?

A

Stimulate macrophage production in the bone marrow

101
Q

Cleavage of ICAD by caspase-3 activates what?

A

CAD, which causes DNA degradation in nuclei

102
Q

HIV specific CD8+ effector T cells produce chemokines and cytokines in order to do what?

A

eliminate infected cells

103
Q

CD4+ T helper cells help to stimulate both dendritic cells and CD8+ T cells to maintain what?

A

CD8 T cell memory response

104
Q

CD8 T cells cooperate with what in the defense against intracellular microbes?

A

CD4 T cells

105
Q

Intracellular bacteria such a L. monocytogenes are phagocytized by Mo but what may happen?

A

They may survive in phagosomes and escape into the cytoplasm

106
Q

CD4 T cells respond to class II MHC-associated peptide Ag derived from the intravesicular bacteria produce what cytokines?

A

IFN-γ and IL-2

107
Q

CD8 T cells respond to what?

A

Class I - associated peptides derived from cytosolic Ags and kill the infected cells

Immunology test III (7 decks)

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