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Immunology Test II > Activation of T lymphocytes > Flashcards

Activation of T lymphocytes Flashcards

1
Q

Naive T lymphocytes recirculate through what?

A

LNs

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2
Q

Activation of naive T cells occurs in LNs if what?

A

They encounter TCR-specific Ags

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3
Q

Ags are transported to LNs from the periphery by what?

A

Mature (activated) DCs

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4
Q

Naive T cells transiently interact with many DCs and stop when?

A

They find specific Ag for TCR

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5
Q

T cells are activated to differentiate into effector cells that are located where?

A

remain in the lympoid organs to help B lymphocytes

migrate to sites of infection to help activate macrophages

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6
Q

Ag recognition by T cells induces what?

A

IL-2 secretion, clonal expansion as a result of cell proliferation, and differentiation of the T cells into effector or memory cells

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7
Q

The effector CD4 T cells respond to Ags by producing what?

A

Cytokines that have several actions, such as the recruitment and activation of leukocytes and activation of B cells

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8
Q

How do the effector CD8 CTLs respond?

A

By killing infected and altered cells

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9
Q

APCs display Ags and provide co-stimulation that guide what?

A

T cell response

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10
Q

Ag recognition together with other activating stimuli induces several responses in T cells including:

A

Secretion of cytokines
Proliferation (clonal expansion)
Differentiation into effector and memory cells

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11
Q

Effector T cells are activated to perform functions that are responsible for what?

A

The elimination of microbes and, in disease states, for tissue damage

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12
Q

T cell responses decline after what?

A

Ag is eliminated

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13
Q

What are long-lived cells with an enhanced ability to react against the Ags?

A

Memory T cells

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14
Q

The proliferation of T lymphocytes and their differentiation into effector and memory cells require what three signals?

A

Signal 1 - Ag recognition
Signal 2 - Costimulation
Signal 3 - Cytokines

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15
Q

What is always the first signal that ensures that the resultant immune response is Ag-specific?

A

Ag

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16
Q

What does activation of naive T cells require?

A

Recognition of Ag presented by DCs

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17
Q

Effector T cells can recognize Ags presented by what?

A

Tissue Mo and B cells

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18
Q

LCK (SRC PTKs) is activated in T cell receptor signaling, this results in what?

A

Phosphorylation of CD3 and activation of ZAP70 (SYK PTK)

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19
Q

What does activated ZAP70 phosphorylate?

A

LAT and SLP76

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20
Q

What does LAT recruit?

A

GRB2, GADS and phospholipase CI (PLC1)

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21
Q

What does the activation of PLC1 result in?

A

The production of inositol 3, 4, 5 - triphosphate (IP3) and diacylglycerol (DAG)

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22
Q

What does IP3 production lead to?

A

Increases of cytosolic free Ca2+

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23
Q

What can DAG activate?

A

Both protein kinase C (PKC)

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24
Q

What does LAT activate?

A

Ras and MAPK

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25
Q

What do superantigens bind simultaneously?

A

MHC class II molecules (not in the peptide-binding groove) and the V region of the β subunit of the TCR

They “glue” T cells to APC and activate the T cell

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26
Q

Superantigens are not processed into what?

A

Not into peptides but are able to bind to a specific family of TCR

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27
Q

What do T cells produce when activated by superantigens?

A

Produce massive amounts of cytokines which might lead to shock

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28
Q

What cause common food poisoning and the toxic shock syndrome toxin (TSST)

A

Staphylococcal enterotoxins (SE) - bacterial superantigens

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29
Q

Resting DC expresses few or no costimulatory molecule levels which are not enough to do what?

A

Activate naive T cells

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30
Q

Ag recognition (signal 1) without costimulation may make T cells what?

A

unresponsive or anergic (tolerant)

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31
Q

Microbes and cytokines produced during innate immune responses (inflammation) activate APCs to do what?

A

Express costimulators, such as B7 molecules, which provide signal 2

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32
Q

The APCs presenting microbial Ags providing signal 2 are now capable of activating what?

A

Naive T cells

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33
Q

What do activated APCs produce that can stimulate the differentiation of naive T cells into effector cells?

A

Cytokines such as IL-12 (signal 3)

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34
Q

What does the best characterized costimulatory pathway in T cell activation involve?

A

The T cell surface receptor CD28, which binds the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) expressed on activated APCs

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35
Q

The expression of B7 costimulators is regulated and ensures what?

A

That T lymphocyte responses are initiated only when needed

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36
Q

CD28 signals work in cooperation with antigen recognition to promote what?

A

The survival, proliferation, and differentiation of the specific T cells

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37
Q

Numerous receptors homologous to CD28 and their ligands homologous to B7 have been identified. These proteins regulate what?

A

T cell responses both positively and negatively

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38
Q

What can the CD28 co-stimulatory receptor can be ligated by what?

A

CD80, CD86, and ICOS-L

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39
Q

The CTLA-4 (cytotoxic T-lymphocyte protein 4) co-inhibitor competes with CD28 for binding to what?

A

CD80 and CD86

40
Q

What can CD80 also bind to and deliver a co-inhibitory signal?

A

PD-L1 (programmed cell death 1 ligand)

41
Q

What does ICOS (inducible T-cell co-stimulator) compete with?

A

With CD28 for binding to ICOS-L?

42
Q

What are naive T cells activated by?

A

Peptide-MHC complexes on activated APCs

43
Q

What does Ag recognition induce?

A

The expression of CD40 ligand (CD40L) on the activated T cells

44
Q

What does CD40L engage on APCs?

A

CD40

45
Q

CD40L engages CD40 on APCs and may stimulate the expression of what?

A

More B7 molecules and the secretion of cytokines that activate T cells

46
Q

What is used to bind to and block B7 molecules?

A

A fusion protein of the extracellular portion of CTLA-4 and the Fc tail of an IgG molecule is used
This prevents their interaction with the activating receptor CD28 and inhibiting T cell activation

47
Q

What binds to and reduces surface expression of the sphingosine 1-phosphate receptor S1PR1?

A

CD69

48
Q

CD69 binding to S1PR1 results in what?

A

Activated T cells retained in lymphoid organs long enough to receive the signals that initiate their proliferation and differentiation into effector and memory cells

49
Q

After T cell division of activated T cells, what expression decreases?

A

CD69

50
Q

The activated T cells re-express high levels of S1PR1 and therefore do what?

A

Effector and memory cells can exit the lymphoid organs

51
Q

Describe expression of CD25 (IL-2Rα) after T cell activation

A

increased and enables activated T cells to respond to the growth-promoting IL-2

52
Q

Describe expression of CD40L (CD154) after T cell activation?

A

Expression is highly increased in activaated T cells within 24 to 48 hours after antigen recognition

53
Q

What does the expression of CD40L enables?

A

Activated T cells to help macrophages and B cells

54
Q

CD40L on the T cells activates what?

A

Dendritic cells to become better APCs, thus providing a positive feedback mechanism for amplifying T cell responses

55
Q

Describe expression of CTLA-4 (CD152) after T cell activation

A

The expression increases within 24 to 48 hours after Ag recognition

56
Q

What does CTLA-4 function as an inhibitor for?

A

T cell activation and thus as a regulator of the response

57
Q

IL-2 is an autocrine growth factor for what cells?

A

CD4 and CD8 T cells

58
Q

What does IL-2 potentiates?

A

cytotoxicity of NK cells and CD8 T cells

59
Q

What does IL-2 co-stimulates?

A

T cells to produce IL-4, IL-5, and IFN-gamma

60
Q

What does IL-2 promote?

A

The development of regulatory T cells

61
Q

What does IL-2 induce?

A

An autocrine activation-induced death in T cells

62
Q

IL-2 stimulates the survival, proliferation, and differentiation of what cells?

A

Antigen-activated T cells

63
Q

IL-2 induces what anti-apoptotic protein?

A

Bcl-2

64
Q

What stimulates cell cycle progression by degradation of the cell cycle inhibitory p27?

A

IL-2

65
Q

What is required for the survival and function of regulatory T cells ?

A

IL-2

66
Q

Knockout mice lacking what have defects in regulatory T cells?

A

IL-2 or IL-2R

67
Q

No other cytokine can replace ____ for the maintenance of functional regulatory T cells.

A

IL-2

68
Q

What has also been shows to stimulate the proliferation and differentiation of NK cells and B cells in vitro?

A

L-2

69
Q

Memory cells may develop from effector cells along a linear pathway, or effector and memory populations that follow what?

A

Divergent differentiation and are two alternative fates of lymphocyes activated by Ag

70
Q

In response to Ag and costimulation, naive T cells differentiate into what?

A

effector and memory cells

71
Q

According to the linear model of memory T cell differentiation, what happens to most effector cells?

A

They die and some survivors develop into the memory population

72
Q

According to the branched differentiation model, effector and memory cells are what?

A

alternative fates of activated T cells

73
Q

T cell-mediated immune responses to an Ags usually results in the generation of memory T cells specific for that Ag, this may persist for how long?

A

Years and even a lifetime

74
Q

The types of transcription factors that are induced during T cell activation may influence what?

A

The fate between the development of effector or memory cells, the mechanisms are unclear

75
Q

What drives differentiation towards development of effector cells in CD4 T cells?

A

T-bet

76
Q

What promotes the generation of memory cells?

A

Blimp-1

77
Q

Memory cells have the ability to survive in a quiescent state without what?

A

Ag

78
Q

What do memory cells express?

A

Increased levels of anti-apoptotic proteins, which may be responsible for their prolonged survival

79
Q

What can memory cells do better than naive cells?

A

Mount larger and enhanced responses

80
Q

Naive T cells respond to Ag in how many days?

A

5 to 7

81
Q

Memory cells respond to At in how many days?

A

1 to 3 days

82
Q

The number of memory T cells specific for any Ag is (lesser/greater) than the number of naive cells specific for the same Ag

A

greater

typically 10- to 1—fold more than the pool of naive cells

83
Q

Memory cells are able to migrate where? What do they express?

A

To peripheral tissues and respond to Ag at the sites

The expression of different adhesion molecules and chemokine receptors

84
Q

What may contribute the the long life span of the memory pool?

A

Memory cells undergo slow self-renewing

85
Q

What is the maintenance of memory cells is dependent on what?

A

cytokines but does not require Ag presence

86
Q

What induces the expression of anti-apoptotic proteins and stimulate low-level proliferation of memory cells?

A

IL-7 and IL-15

87
Q

What are the phenotypic markers for memory T cells?

A

IL-7R, CD45 and CD27 (function unknown)

88
Q

What are CD4 and CD8 memory T cells subdivided into?

A

Subsets based on their homing properties and functions

89
Q

Central memory T cells express what chemokine recepetor, selectin, and where does it mainly home?

A

CCR7 and L-selection and home mainly to LNs

90
Q

What do effector memory T cells home to?

A

mucosal tissues

91
Q

Effector memory T cells do not proliferate but produce what?

A

Cytokines IFN-γ or become cytotoxic

92
Q

Elimination of Ag leads to what?

A

contraction of the T cell response

93
Q

What is the decline of T cell response responsible for?

A

Maintaining homeostasis in the immune system

94
Q

As the level of costimulation and IL-2 decrease, what happens to the levels of anti-apoptotic proteins in the cells?

A

It drops

95
Q

IL-2 starvation triggers what?

A

The mitochondrial pathway of apoptosis

96
Q

What various regulatory mechanisms contribute to the normal contraction of immune responses?

A

Inhibitory receptors CTLA-4 and PD-1
Apoptosis induced by death receptors TNFRI and Fas
Regualtory T cells

Immunology Test II (7 decks)

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