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Immunology > Lecture 11 (Exam 2) > Flashcards

Lecture 11 (Exam 2) Flashcards

1
Q

Naive T lymphocytes recirculate through…

A

Lymph nodes (LNs)

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2
Q

Activation of naive T cells occurs in LNs if they encounter…

A

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 they find the specific _____ for their TCR.

A

Ag

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5
Q

The T cells are activated to differentiate into ________ cells. Then activated T cells may –

    • remain in the lymphoid organs to help _________
    • migrate to sites of infection to help activate _________
A

Effector
B lymphocytes
Macrophage

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6
Q

Ag recognition by T cells induces ______ secretion, clonal expansion as a result of cell proliferation and differentiation of the T cells into _______ or _______ cells.

A

IL-2
Effector
Memory

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7
Q

The effector (CD4+/CD8+) 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

CD4+

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8
Q

The effector (CD4+/CD8+) CTLs function by killing infected and altered host cells.

A

CD8+

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9
Q

T/F. APCs display Ags and provide co-stimulatory signals that guide T cell response.

A

True

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10
Q

Ag recognition accompanied by co-stimulation induces several responses in T cells, which are…

A

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

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11
Q

(MEMORY/EFFECTOR) T cells are activated to perform functions that are responsible for elimination of microbes and, in disease states, for tissue damage.

A

Effector

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12
Q

T cell responses ________ after the Ag is eliminated.

A

Decline

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13
Q

Generated (MEMORY/EFFECTOR) T cells are long-lived cells with an enhanced ability to react against the Ags.

A

Memory

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14
Q

The proliferation of T lymphocytes and their differentiation into effector and memory cells require three signals, which are…

A

Ag recognition (signal 1)
Costimulation (signal 2)
Cytokines (signal 3)

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15
Q

Ag is always the first signal that ensure that the resultant immune response is ________.

A

Ag-specific

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16
Q

Activation of naive T cells requires recognition of Ag presented by _______.

A

DCs (dendritic cells)

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17
Q

The effector T cells can recognize Ags presented by tissue ________ and _______.

A

Macrophages

B cells

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18
Q

Unactivated (immature) ______ express low levels of costimulatory molecules which are not enough to activate naive T cells.

A

DCs

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19
Q

T/F. Ag recognition (signal 1) with costimulation may make T cells unresponsive or anergic (tolerant).

A

False. WITHOUT costimulation, T cells may be unresponsive or anergic.

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20
Q

Microbes and cytokines produced during innate immune responses (inflammation) activate DCs to express costimulators, such as _______ molecules, which provide costimulatory signal 2.

A

CD80/86

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21
Q

Activated DCs also produce cytokines such as ______ (signal 3), which stimulate the differentiation of naive T cells into effector cells.

A

IL-12

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22
Q

The best characterized costimulatory pathway in T cell activation involves the T cell surface receptor ______, which binds the costimulatory molecules ______ and _____ expressed on activated APCs.

A

CD28
B7-1 (CD80)
B7-2 (CD86)

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23
Q

The expression of _____ costimulators is regulated and ensures that T lymphocyte responses are initiated only when needed.

A

B7

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24
Q

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

A

CD28

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25
Q

Numerous receptors homologous to ______ and their ligands homologous to _____ have been identified, and these proteins regulate T cell responses both positively and negatively.

A

CD28

B7

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26
Q

The outcome of T cell activation is influenced by a balance between engagement of activating and inhibitory receptors of the ______ family.

A

CD28

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27
Q

_____-mediated immune checkpoint is induced in naive T cells at the time of their initial response to Ag.

A

CTLA-4

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28
Q

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

A

CD28

CTLA-4

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29
Q

After the TCR is triggered by Ag encounter, ______ is transported to the cell surface.

A

CTLA-4

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30
Q

The stronger the stimulation through the _____ and _____, the greater the amount of CTLA-4 that is deposited on the T cell surface.

A

TCR

CD28

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31
Q

Therefore, CTLA-4 functions as a signal ________ to maintain a consistent level of T cell activation.

A

Dampener

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32
Q

The major role of the _____ pathway is not at the initial T cell activation stage but rather to regulate inflammatory responses in tissues by effector T cells recognizing Ag in peripheral tissues.

A

PD1 (Programmed cell death protein 1)

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33
Q

Activated T cells upregulate _____ and continue to express it in tissues. Inflammatory signals in the tissues induce the expression of _____ ligands.

A

PD1

PD1

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34
Q

_____ ligands down regulate the activity of T cells and thus limit collateral tissue damage in response to a microorganism infection in that tissue.

A

PD1

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35
Q

The best characterized signal for PD-L1 induction is _____ cell-derived from Th1 cells.

A

IFN-y

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36
Q

Excessive induction of _____ on T cells in the setting of chronic antigen exposure can induce an exhausted or anergic state in T cells.

A

PD1

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37
Q

Upon T cell activation, cytokines in the T cell microenvironment determine the outcome of Ag recognition with regard to ________ T cell differentiation.

A

Effector

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38
Q

IL-12 activates ______ that leads to expression of ______ which facilitates the generation of Th1 cells.

A

STAT4

T-bet

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39
Q

IL-4 activates ______ that leads to the expression of ______ which facilitates the generation of Th2 cells.

A

STAT6

GATA3

40
Q

IL-6 activates ______ that leads to the expression of ______ which facilitates the generation of Th17 cells.

A

STAT3

RORyt (Retinoic acid receptor-related orphan receptor-yt)

41
Q

TGF-B activates _______ which promotes the expression of _______ and the generation of T regulatory cells.

A

SMAD2-SMAD4

FOXP3

42
Q

_________ produced by some bacteria are the most powerful T cell mitogens ever discovered.

A

Superantigens (SAgs)

43
Q

Less than 0.1 pg/ml of a SAg are sufficient to stimulate the T cells in an uncontrolled manner resulting in fever, shock, and death. SAgs are not processed into ________.

A

Peptides

44
Q

T/F. SAgs simultaneously bind MHC class II molecules (not in the peptide-binding groove) and the V region of the Beta subunit of the TCR.

A

True

45
Q

T/F. Superantigens bind ONLY to some Beta subunits of the TCR, not all.

A

True

46
Q

SAgs prolongedly “glue” _____ to _____ and this interaction activate T cells.

A

T cells

APCs

47
Q

SAgs induce a robust proliferation of SAgs-activated T cells which produce massive amounts of pro inflammatory cytokines (_____, ______, and _____) which may lead to shock.

A

TNF
IL-1
IL-2

48
Q

______ ______ are bacterial SAgs that cause common food poisoning and the toxic shock syndrome toxin (TSST).

A

Staphylococcal enterotoxins (SE)

49
Q

Biologic actions of IL-2 —-

1) IL-2 is an ________ growth factor for CD4+ and CD8+ T cells.
2) Potentiates _________ of NK cells and CD8+ T cells.
3) Co-stimulates T cells to produce IL-4, IL-5, and IFN-y.
4) Promotes the development of T regulatory cells.
5) Induces an autocrine activation-induced death in T cells.

A

Autocrine

Cytotoxicity

50
Q

IL-2 stimulates the survival, proliferation, and differentiation of Ag-activated T cells. IL-2 induces the anti-apoptotic protein ______. It stimulates cell cycle progression by degradation of the cell cycle inhibitor ______.

A

Bcl-2

p27

51
Q

IL-2 is required for the survival and function of _____ cells. IL-2 -/- or IL-2R -/- knockout mice have selective defects in _____ cells. No other cytokine can replace IL-2 for the maintenance of these cells.

A

Treg

Treg

52
Q

IL-2 has also been shown to stimulate the proliferation and differentiation of NK cells and B cells _______.

A

In vitro

53
Q

Disruption of the IL-2 pathway results in lymphoid hyperplasia and autoimmunity rather than immune deficiency, indicating that the major physiological function of IL-2 is to (ENHANCE/LIMIT) rather than (ENHANCE/LIMIT) T cell responses.

A

Limit

Enhance

54
Q

T/F. It was discovered that IL-2 is critical for the development and peripheral expansion of CD4+ CD25+ regulatory T cells, which promote peripheral self-tolerance by suppressing T cell responses in vivo.

A

True

55
Q

T cells and B cells egress from LNs requires _______.

A

S1PR1 (Sphingosine 1-phosphate receptor)

56
Q

If T cell or B cell is activated by Ag, ______ associates with and inhibits the function of S1P(1), inhibiting egress.

A

CD69

57
Q

______ binding reduces surface expression of the receptor S1PR1.

A

CD69

58
Q

As a result of CD69 reducing S1PR1 expression, activated T cells are retained in the LNs long enough to receive the signals that initiate their proliferation and differentiation into _______ and _______ cells. After cell division, CD69 expression (INCREASES/DECREASES).

A

Effector
Memory
Decreases

59
Q

The activated T cells re-express high levels of _______, and therefore effector and memory cells can exit the lymphoid organs.

A

S1PR1

60
Q

Without Ag activation, S1PR1 is re-expressed and naive lymphocytes leave the LN by mechanism of ________ towards a high concentration of S1P in the lymph.

A

Chemotaxis

61
Q

T and B cells stay in the LNs until S1P1 receptor is re-expressed on cell membrane. Lymphocytes in the ______, which has abundant extracellular S1P, have little surface S1P1.

A

Blood

62
Q

After migration into a ______ ______, the cells begin to up-regulate S1P1, because extracellular S1P concentrations are no longer adequate to cause receptor down-modulation. Only when S1P1 is up-regulated do the cells become fully egress competent and the time required for up-regulation may help ensure that the cells dwell in the tissue for a period of hours.

A

Lymph node (LN)

63
Q

Expression of ______ occurs in Ag-activated T cells only. An increased expression enables activated T cells to respond to IL-2 by proliferation.

A

CD25 (IL-2Ra)

64
Q

Ag recognition induces the expression of ______ ligand on the activated T cells. Expression of this is highly increased in activated T cells within 24 to 48 hours after Ag recognition.

A

CD40L (CD154)

65
Q

The expression of CD40L enables activated T cells to help _____, ______, and ______ to become better APCs.

A

DCs
Macrophages
B cells

66
Q

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

A

CD40

B7

67
Q

Elimination of Ag leads to ________ of the T cell response. Decline is responsible for maintaining homeostasis in the immune system.

A

Contraction

68
Q

As the level of costimulation and IL-2 decrease, the levels of _________ proteins in the cells drop.

A

Anti-apoptotic

69
Q

IL-2 starvation triggers the mitochondrial intrinsic pathway of ________.

A

Apoptosis

70
Q

Various regulatory mechanisms contribute to the normal contraction of immune responses:

    • The inhibitory receptors ______ and ______
    • Apoptosis induced by death receptors ______ and _____
    • Inhibition by Treg cell products
A

CTLA-4
PD-1
TNFRI
Fas

71
Q

(MEMORY/EFFECTOR) cells may develop from (MEMORY/EFFECTOR) cells along a linear pathway, or effector and memory populations follow divergent differentiation and are two alternative fates of lymphocytes activated by Ag.

A

Memory

Effector

72
Q

According to the _______ model of memory T cell differentiation, most effector cells die and some survivors develop into the memory cells. Recent findings are more consistent with this model.

A

Linear

73
Q

According to the _______ differentiation model, effector and memory cells are alternative fates of activated T cells.

A

Branched

74
Q

T cell-mediated immune responses to an Ags usually result in the generation of (EFFECTOR/MEMORY) T cells specific for that Ag, which may persist for years, even a lifetime.

A

Memory

75
Q

(EFFECTOR/MEMORY) T cells constitute the most abundant lymphocyte population in the body during lifetime.

A

Memory

76
Q

The vast majority of memory T cells reside in tissue sites, including…

A

Lymphoid tissues
Intestines
Lungs
Skin

77
Q

The types of transcription factors that are induced during T cell activation may influence the fate between the development of effector or memory cells. The ______ drives differentiation of effector cells in CD4+ T cells, and ______ promotes the generation of memory cells.

A

T-bet

Blimp-1

78
Q

T/F. CD4+ and CD8+ effector T cells are subdivided into subsets based on their homing properties and functions.

A

False. CD4+ and CD8+ MEMORY cells are subdivided into subsets based on their homing properties and functions.

79
Q

The ______ memory T cells produce IFN-y and TNF and are specific for pathogens and other Ags that have been encountered previously through that barrier epithelium.

A

Resident (T-RM)

80
Q

The _______ memory T cells express the chemokine receptor CCR7 and L-selectin and home mainly to LNs, spleen, and circulate in the blood.

A

Central (T-CM)

81
Q

Upon Ag re-exposure, T-CM cells proliferate (high production of IL-2) and generate many ________ cells.

A

Effector

82
Q

The _______ memory T cells circulate in the blood. They do not proliferate but produce IFN-y and TNF or become cytotoxic.

A

Effector (T-EM)

83
Q

Upon entering the tissue, T-EM cells can become ______ cells and reside in epithelial barrier tissues at the interface between the host and the environment.

A

T-RM

84
Q

Memory cells have the ability to survive in a _______ state without the Ag.

A

Quiescent

85
Q

Memory cells express increased levels of _________ proteins, which may be responsible for their prolonged survival.

A

Anti-apoptotic

86
Q

Memory cells are able to mount larger and enhanced responses to Ag than do _______ cells.

A

Naive

87
Q

Naive T cells respond to Ag in ______ days whereas memory cells respond within ______ days.

A

5 to 7

1 to 3

88
Q

The number of (MEMORY/NAIVE) T cells specific for any Ag is greater than the number of (MEMORY/NAIVE) T cells specific for the same Ag. Typically 10- to 100-fold more.

A

Memory

Naive

89
Q

Memory T cells pass through three distinct phases, which are…

A

Memory generation
Memory homeostasis
Immunosenescence

90
Q

Memory T cells are mostly generated following Ag exposure during ______, _______, and _______ _______. (Memory generation phase)

A

Infancy
Youth
Young Adulthood

91
Q

After memory generation phase, memory T cell levels subsequently plateau and are maintained through ________ throughout adulthood (30-65 years), after which time they show senescent changes (age >65 years).

A

Homeostasis

92
Q

Memory cells are able to migrate to peripheral tissues and respond to Ag at the sites. The expression of different ________ ________ and ________ ________ navigate cell movement in the tissues.

A

Adhesion molecules

Chemokine receptors

93
Q

T/F. Memory cells undergo slow self-renewing, which may contribute to the long life span of the memory pool.

A

True

94
Q

The maintenance of memory cells is dependent on ________ but does not require Ag presence.

A

Cytokines

95
Q

Environmental ______ and ______ cytokines induce the expression of anti-apoptotic proteins and stimulate low-level proliferation.

A

IL-7

IL-15

Immunology (10 decks)

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