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Immunology - Unit 2 - Zach H. > Activation of T Lymphocytes > Flashcards

Activation of T Lymphocytes Flashcards

1
Q

Where does activation of naive T cells occur if they encounter TCR-specific Ags?

A

LNs

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2
Q

What cell presents Ags to naive T cells in LNs?

A

Ags that are transported to LNs from the periphery by mature (activated) DCs.

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3
Q

What are the two possible functions of activated T cells that differentiate into effector cells?

A
  • remain in the lymphoid organs to help B lymphocytes

- migrate to sites of infection to help activate macrophages

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4
Q

What cytokine is secreted by T cells that recognize an Ag?

A

IL-2

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5
Q

What is clonal expansion a result of?

A

Result of cell proliferation and differentiation of the T cells into effector or memory cells.

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6
Q

True or False:

The effector CD4+ T cells respond to Ags by producing cytokines that have several actions, such as the recruitment and activation of leukocytes and activation of B cells.

A

True

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7
Q

How do effector CD8+ CTLs respond?

A

By killing infected and altered host cells.

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8
Q

List the phases of T cell responses.

A

> APCs display Ags and provide co-stimulation that guide T cell response.

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

 - secretion of cytokines
 - proliferation (clonal expansion)
 - differentiation into effector and memory cells

> Effector T cells are activated to perform functions that are responsible for the elimination of microbes andd, in disease states, for tissue damage.

> T cell responses decline after the Ag is eliminated.

> Generated memory T cells are long-lived cells with an enhanced ability to react against the Ags.

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9
Q

What are the 3 signals that are required for proliferation of T lymphocytes and their differentiation into effector and memory cells?

A

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

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10
Q

What APCs can effector T cells recognize Ags from?

A

> macrophages

> B cells

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11
Q

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

A

Ag is always the FIRST SIGNAL.

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12
Q

Look over T-cell Receptor Signaling pathway.

A

Slide 11

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13
Q

What do superantigens bind to simultaneously?

A
  • MHC class II molecules (not in the peptide-binding groove)

- V region of the beta subunit of the TCR

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14
Q

Are superantigens processed into peptides?

A

No

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15
Q

What do superantigens do to activate T cells?

A

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

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16
Q

Give an example of a bacterial superantigen.

A

Staphylococcal enterotoxins (SE) are bacterial superantigens that cause common food poisoning and the toxic shock syndrome toxin (TSST).

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17
Q

How can superantigens cause shock?

A

They “glue” T cells to APC and activate the T cell. Thus, causing T cells to produce massive amounts of cytokines which may lead to shock.

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18
Q

What does an Ag recognition (signal 1) without costimulation for T cells result in?

A

May make T cells unresponsive or anergic (tolerant).

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19
Q

What are the most powerful T cell mitogens ever discovered?

A

Superantigen (SAgs)

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20
Q

How do SAgs interact with T cells?

A

SAgs bind, as intact molecules to the class II MHC expressed on professional APCs outside the peptide-binding groove then sequentially bind the TCR via the variable region of the beta-chain.

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21
Q

Which pro-inflammatory cytokines are massively systemically released in response to SAgs and can lead to fever and shock?

A
  • TNF-alpha
  • IL-1 beta
  • IL-2
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22
Q

True or False:

Resting DCs express few or no costimulatory molecules levels of which are not enough to activate naive T cells.

A

True

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23
Q

What provides signal 2 needed for T cell activation?

A

microbes and cytokines produced during innate immune responses (inflammation) activate APCs to express costimulators, such as B7 molecules, which provide signal 2.

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24
Q

What costimulatory molecules expressed on activated APCs bind to T cell surface receptor CD28?

A

> B7-1 (CD80)

> B7-2 (CD86)

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25
Q

Fill in the Blank:

CD28 signals work in _____ with Ag recognition to promote the survival, proliferation, and differentiation of the specific T cells.

A

cooperation

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26
Q

True or False:
The outcome of T cell activation is influenced by a BALANCE between engagement of activating and inhibitory receptors of the CD28 family.

A

True

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27
Q

What immune checkpoint is induced in naive T cells at the time of their initial response to Ag?

A

CTLA4-mediated immune checkpoint

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28
Q

Naive and memory T cells express high levels of what cell surface protein, and do not express what protein that is stored in intracellular vesicles?

A

Naive and memory T cells express high levels of cell surface CD28 but do not express CTLA4 which is stored in intracellular vesicles.

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29
Q

What causes the transport of CTLA4 to the cell surface?

A

TCR being triggered by Ag encounter.

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30
Q

What does CTLA4 function to do?

A

Functions as a signal dampener to maintain a consistent level of T cell activation.

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31
Q

True or False:

The stronger the stimulation through the TCR (and CD28), the greater the amount of CTLA4 that is deposited on the T cell surface.

A

True

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32
Q

What is the major role of the programmed cell death protein 1 (PD1)?

A

Regulate inflammatory responses in tissues by effector T cells recognizing Ag in peripheral tissues.

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33
Q

Fill in the Blank:

Activated T cells _____ _____ and continue to express it in tissues.

A

upregulate PD1

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34
Q

What signals induce the expression of PD1 ligands?

A

Inflammatory Signals

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35
Q

What control does PD1L regulate in the activity of T cells?

A

PD1L downregulate the activity of T cells and thus limit collateral tissue damage in response to a microorganism infection in that tissue.

36
Q

The best characterized signals for PD1L induction is ______ cell-derived from Th1 cells.

A

IFN-gamma

37
Q

What can excessive induction of PD1 on T cells in the setting of chronic antigen exposure do?

A

Can induce an exhausted or anergic state in T cells.

38
Q

True or False:

PD-1 is a rheostat for immune responses.

A

True

39
Q

What is the autocrine IL-2 a growth factor for?

A

> CD4+

> CD8+

40
Q

Which two cell types does IL-2 potentiate cytotoxicity in?

A

> NK cells

> CD8+ T cells

41
Q

What does IL-2 co-stimulate T cells to produce?

A

> IL-4
IL-5
IFN-gamma

42
Q

Which cytokine promotes the development of regulatory T cells?

A

IL-2

43
Q

Can IL-2 induce an autocrine activation-induced death in T cells?

A

Yes (see CTLA-4)

44
Q

What anti-apoptotic protein is induced by IL-2?

A

Bcl-2

45
Q

Which cytokine stimulates cell cycle progression by degradation of the cell cycle inhibitor p27?

A

IL-2

46
Q

True or False:

IL-2 is required for the survival and function of Treg cells.

A

True

** NO other cytokine can replace IL-2 for the maintenance of functional Treg cells **

47
Q

True or False:

IL-5 stimulates the survival, proliferation, and differentiation of Ag-activated T cells.

A

False - IL-2 does.

48
Q

In vitro, which cytokine has been shown to simulate the proliferation and differentiation of NK cells and B cells?

A

IL-2

49
Q

What is the function of newly-expressed CD69 on T cells?

A

retention in lymph node

50
Q

What is the function of newly-expressed IL-2R alpha (CD25) on T cells?

A

proliferation

51
Q

What is the function of newly-expressed CD40L on T cells?

A

Activation of DCs, Macrophages, and B cells

52
Q

What is the function of newly-expressed CTLA-4 on T cells?

A

control of response

53
Q

What is the result of CD69 binding to and reducing surface expression of the sphingosine 1-phophate receptor S1PR1 in T cell activation?

A

Activated T cells are RETAINED in the LNs long enough to receive the signalsthat initiate their proliferation and differentiation into effector and memory cells.

54
Q

When does CD69 expression decrease on T cells?

A

after cell division

55
Q

The re-expression to high levels of which receptor allows activated T cells (effector and memory cells) to exit the lymphoid organ?

A

S1PR1

56
Q

The expression of which protein enables activated T cells to respond to growth-promoting IL-2?

A

CD25 (IL-2Ralpha)

57
Q

What causes the expression of CD40L on activated T cells?

A

Ag recognition induces expression of CD40L on activated T cells (can be with or without B7 co-stimulators).

58
Q

The expression of CD40L (CD154) is highly increased in ctivated T cells within how many hours after Ag recognition?

A

24 - 48 hours

** CTLA-4 (CD152) also increases within 24 - 48 hours after Ag recognition **

59
Q

The expression of which ligand on activated T cells enables activated T cells to help DCs, macrophages, and B cells to become better APCs?

A

CD40L

60
Q

True or False:

The CD40L engages CD40 on APCs and may stimulate the expression of more B7 molecules and the secretion of cytokines that activate T cells.

A

True

61
Q

What does CTLA-4 do?

A

Functions as an inhibitor of T cell activation and thus as a regulator of the response.

62
Q

What part of the T cell response is responsible for maintaining homeostasis in the immune system?

A

Decline of T cell response.

63
Q

What happens as the level of co-stimulation and IL-2 decrease?

A

Levels of anti-apoptotic proteins in the cells drop.

64
Q

What triggers the mitochondrial pathway of apoptosis in the decline of T cell response?

A

IL-2 Starvation

65
Q

In addition to IL-2 starvation griggering the mitochondrial pathway of apoptosis, the addition of whay other regulatory mechanisms contribute to the normal contraction of immune responses?

A

> inhibitory receptors CTLA4 and PD-1
apoptosis induced by death receptors TNFRI and Fas
Treg cells

66
Q

True or False:

Memory cells may develop from effector cells along a linear pathway, or effector and memroy populations follow divergent differentiation and are two alternative fates of lymphocytes activated by Ag.

A

True

67
Q

In the development of memory T cells, what are the two outcomes according to the linear model of memory T cell differentiation?

A

> most effector cells die

> some survivors develop into the memory cells

68
Q

In the development of memory T cells, what is the outcome according to the branched differentiation model?

A

Effector and memory cells are alternative fates of activated T cells.

69
Q

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

A

> effector T cells

> memory T cells

70
Q

What cell type constitutes the most abundant lymphocyte population in the body for the majority of a person’s lifetime?

A

memory T cells

71
Q

Where do the vast majority of memory T cells reside?

A

Tissue sites, including lymphoid tissues, intestines, lungs and skin.

72
Q

What drives differentiation of effector cells in CD4+ T cells?

A

T-bet

73
Q

What protein promotes the generation of memory T cells?

A

Blimp-1

74
Q

What is responsible for the prolonged survival of memory T cells?

A

They express increased levels of anti-apoptotic proteins.

75
Q

How quickly do memory T cells respond to Ags compared to naive T cells?

A

Naive T cells respond to Ag in 5 -7 days.

Memory T cells respond to Ag in 1 - 3 days.

76
Q

True or False:

The number of memory T cells specific for any Ag is greater than the number of naive cells specific for the same Ag.

A

True

typically 10- to 100-fold more than the pool of naive cells

77
Q

What does the maintenance of memory T cells depend on? Also, what does it not require that naive T cells do?

A

Dependent on -> cytokines

Does not require -> Ag presence

78
Q

Which cytokines induce the expression of anti-apoptotic proteins and stimulate low-level proliferation in memory T cells?

A

IL-7

IL-15

79
Q

True or False:

Memory cells are able to migrate to peripheral tissues and respond to Ag at the sites.

A

True

80
Q

What are the 3 distinct phases that memory T cells pass through?

A

1) memory generation
2) memory homeostasis
3) immunosenescence

81
Q

During which portion of a lifespan does memory T cells mostly generate following Ag exposure?

A
  • during infancy
  • during youth
  • during young adulthood (0-20 years)
82
Q

When do memory T cells typically show sensescent changes?

A

> 65 years

**memory T cell levels subsequently plateau and are maintained through homeostasis throughout audlthood (30-65 years), after which time they show senescent changes (age >65 years).

83
Q

What are the 3 phenotypic markers for memory T cells?

A
  • IL-7R
  • CD45
  • CD27 (function is unknown)
84
Q

What are the two subsets that CD4+ and CD8+ memory T cells are divided into based on their homing properties and functions?

A

> CENTRAL memory T cells (Tcm cells) express the chemokine receptor CCR7 and L-selectin and home mainly to LNs, spleen and circulate in the blood.
- Proliferate (high production of IL-2) and generate many effector cells on Ag challenge.

> EFFECTOR memory T cells (Tem cells) circulate in the blood.
- DO NOT proliferate but produce IFN-gamma and TNF or become cytotoxic.

85
Q

Do effector memory T cells (Tem cells) proliferate?

A

NO - but produce IFN-gamma and TNF or become cytotoxic.

86
Q

What are resident tissue memory T cells (Trm cells) and what do they produce?

A

RESIDENT tissue memory T cells (Trm cells) reside in epithelial barrier tissues at the interface between the host and the environment.
- Trm cells produce IFN-gamma and TNF and are specific for pathogens and other Ags that have been encountered previously through that barrier epithelium.

87
Q

Review Slide 44

A

role of Trm cells in tissue-specific autoimmune and inflammatory disease

Immunology - Unit 2 - Zach H. (3 decks)

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