Lecture 13 (Exam 2) Flashcards

1
Q

(CD4/CD8) T cells are class I MHC-restricted.

A

CD8+

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2
Q

Naive CD8+ T cells recognize peptide Ags presented by _____ in the lymph nodes.

A

DCs

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3
Q

CD8+ T cells are stimulated to proliferate and differentiate into _____ (and memory cells).

A

CTLs (Cytotoxic T lymphocytes)

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4
Q

CD8+ ______ enter the circulation and migrate to the site of Ag acquisition. They recognize the Ag in the tissues and respond by killing the target cells where the Ag is produced.

A

CTLs

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5
Q

Naive CD8+ cells recognize Ags (signal 1) and proliferate and differentiate into effector CTLs upon _____-_____ costimulation (signal 2).

A

CD28-CD80

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6
Q

Activated CTLs contain numerous granules called ________ that contain _______ and _______ used by the cells to kill other cells.

A

Lysosomes
Perforin
Granzymes

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7
Q

Activated CTLs secrete cytokines, mostly ______, that potently activate macrophages.

A

IFN-y

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8
Q

Similar to activation of Th1 cells, the molecular events of CTL differentiation involve transcriptional factor ______.

A

T-bet

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9
Q

For CTLs, T-bet regulated transcription of genes encoding…

A

Perforin
Granzymes
IFN-y

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10
Q

Cells infected with intracellular microbes, such as viruses, are ingested by ______.

A

DCs

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11
Q

Extracellular Ags are processed and presented within _______, but they are also presented in association with _______ by the mechanism called Ag cross-presentation.

A
class II MHC
class I MHC
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12
Q

Some viral Ags are released from phagosome in the cytoplasm of DC and then presented within class I MHC. The same cross-presenting APC also display microbial peptides within class II MHC for _______ T cells.

A

CD4+ helper

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13
Q

Generation of CD4+ effector T cells ________ the appearance of CD8+ T cells. It happens this way because DCs need “________” or “________” (done by CD4+ T cells).

A

Precedes
Education
Licensing

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14
Q

Licensing of the APC occurs when the CD4+ T cell delivers activating signals through (1) _____/_____ signaling and (2) cytokines (____) to DC after it recognizes Ag presented by an MHC class II APC.

A

CD40L/CD40

IFN-y

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15
Q

Activated CD4+ Th cells increase expression of ______, which may bind to ______ on Ag-loaded DCs.

A

CD40L

CD40

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16
Q

The CD40-CD40L and IFN-y interaction up regulates expression of ______/______ on and stimulates Ag cross-presentation which makes them more efficient at inducing differentiation of CD8+ T cells.

A

CD80/CD86

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17
Q

______ stimulates T cell proliferation because its receptor shares the common gamma-chain with IL-2.

A

IL-15

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18
Q

DC licensing occurs when CD4+ helper T cells enhance the ability of _____ to stimulate _____ differentiation.

A

APCs

CTL

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19
Q

IL-2 promotes proliferation and differentiation of CD8+ T cells into CTLs and memory cells. Activated CD8+ T cells express high levels of the alpha subunit of IL-2R. IL-2R shares the y (gamma) chain with ______ and ______.

A

IL-15R

IL-21R

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20
Q

_____ and _____ stimulate the differentiation of naive CD8+ T cells into effector CTLs. Naive CD8 T cells proliferate in response to TCR and CD28 signals, but require _____ or _____ for survival and development of optimal effector functions.

A

IL-12
IFN-y
IL-12
IFN-y

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21
Q

_____ may be produced by DCs and tissue macrophages. It is important for the survival of memory CD8+ T cells. Mice lacking this show a significant loss of memory CD8+ T cells.

A

IL-15

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22
Q

_____ produced by activated CD4+ T cells play a role in the induction of CD8+ T cell memory and the prevention of CD8+ T cell exhaustion.

A

IL-21

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23
Q

CD4+ T cell-derived ______ is originally known as T cell growth factor due to its effects on lymphocyte activation and proliferation.

A

IL-2

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24
Q

The key feature of IL-2 is the ______ ______ through which it operates.

A

Autocrine loop

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25
Q

Local release of IL-2 can lead to clonal expansion of T cells which upon recognition of Ag presented by APC express _____ _____ of IL-2R.

A

Alpha subunit

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26
Q

Local release of IL-2 by activated CD4+ T cells leads to activation of nearby Ag-activated CD8+ T cells in a ________ fashion.

A

Paracrine

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27
Q

T cell-derived ______ is a homodimer composed of subunits of approximately 25 kDa. It is released by Th1 cells and CTLs, as well as by activated NK cells.

A

IFN-y

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28
Q

IFN-y is a potent activator of ________ inducing an increase in metabolic, phagocytic, and killing activity.

A

Macrophages

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29
Q

IFN-y has the ability to increase ________ molecule expression on a range of cell types and induce expression of _______ molecules on professional APCs. This may be an important component of antiviral protection, since it up-regulates Ag presentation of viral targets by infected cells.

A

Class I MHC

Class II MHC

30
Q

IFN-y favors the development of Th1 cells and B cell differentiation biasing the production of immunoglobulin in favor of _____ and away from _____.

A

IgG

IgE

31
Q

Professional APC-derived ______ is a key cytokine produced by activated DCs and macrophages. It has the profound effect of inducing differentiation of naive CD4 T cells into Th1 effector cells.

A

IL-12

32
Q

IL-12 thus promotes production of the pro-inflammatory cytokines _____ and _____ by CD4+ T and CD8+ T cells.

A

IFN-y

TNF-B

33
Q

T/F. IL-12 stimulated CD8+ T cells are more effective in controlling tumor and they maintain high numbers and function as compared to IFN-y stimulated cells.

A

True

34
Q

_____ assists in prevention of CD8+ T cells exhaustion and also activates NK cells.

A

IL-12

35
Q

Professional APC-derived ______ is from activated macrophages and mature DCs. It has similar biologic properties with IL-2 which is consistent with their shared receptor (R) signaling components.

A

IL-15

36
Q

IL-15 was first identified as a T-cell growth factor through its ability to promote the proliferation of ______.

A

CTLs

37
Q

Exogenous IL-15 favors human _____ T-cell differentiation in vitro.

A

Th1

38
Q

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

A

Chemoattractant

39
Q

T/F. IL-15 promotes proliferation of memory CD4+ and CD8+ and naive CD8+ T cells.

A

True

40
Q

IL-15 has been shown to costimulate innate immune _____ production.

A

IFN-y

41
Q

______ is a pleiotropic cytokine with actions on a broad range of lymphoid, myeloid, and epithelial cells. These actions include effects on proliferation, survival, differentiation, and function.

A

IL-21

42
Q

IL-21 has a key role in B cell differentiation into ______ cells and in the development of ________ helper cells.

A

Plasma

T follicular

43
Q

______ induces a functional program in CD8+ T cells that leads to enhanced survival, antiviral activity, and anti tumor activity.

A

IL-21

44
Q

IL-21 has a key role in the development of _____ cells, which contribute to pathogenesis in a range of inflammatory diseases.

A

Th17

45
Q

Clinical trials with IL-21 alone or in combination with other agents have yielded favorable results in the treatment of solid _______.

A

Tumors

46
Q

IL-21 promotes a range of autoimmune diseases, including systemic lupus erythematosus, type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and psoriasis. Clinical trials using IL-21 _______ are in progress.

A

Inhibitors

47
Q

In acute infections, _____ T cells differentiate into _____ that eliminate the infected cells.

A

CD8+

CTLs

48
Q

1) DCs present viral Ags to CD8+ T cells.
2) This initiates clonal expansion and differentiation into CTLs.
3) Activated CTLs secrete pro-inflammatory _____, _____, and cytotoxic ______ and ______.
4) After viral clearance, the CD8+ T cells undergo an extensive contraction phase, mediated by apoptosis.
5) The memory CD8+ T cells (T-CM, T-EM, T-RM) and generated and can persist in the host for years.

A

TNF-B
IFN-y
Perforin
Granzymes

49
Q

In the event of a secondary exposure to the same virus, memory CD8+ T cells can rapidly expand acquire _______ functions.

A

Effector

50
Q

In some chronic viral infections, the responses of CD8+ T cells may be initiated but gradually extinguished, a phenomenon that is called ________. This is an active suppression of immune responses first described in a chronic viral infection.

A

Exhaustion

51
Q

Exhausted CD8+ T cells show reduced production of ______ and increased expression of ______ inhibitory receptor.

A

IFN-y

PD-1

52
Q

Inhibitory signals from PD-1 and CTLA-4 block activation of ______.

A

CTLs

53
Q

PD-1 mediated T cell exhaustion may contribute to the chronicity of ______ and ______ virus.

A

HIV

Hep C

54
Q

Anti-PD-1 and anti-CTLA-4 Abs are effective in the immuno-therapy of _______.

A

Tumors

55
Q

In Fas-FasL-mediated apoptosis, the (FAS/FASL) is expressed on activated CTLs, engages (FAS/FASL) on the surface of target cells, and induces apoptosis.

A

FasL

Fas

56
Q

In granzyme-mediated apoptosis, complexes of perforin and granzymes are released from the _____ by granule exocytosis and enter target cells. The granzymes are delivered into the cytoplasm of the target cells by a perforin-dependent mechanism, and they induce apoptosis.

A

CTL

57
Q

In Fas-FasL mediated apoptosis, the binding of FasL to Fas recruits _________ through the _______ adaptor converts it into the active enzyme ________.

A

Procaspase-8
FADD
Caspase-8

Study Lecture 13 Slide 35

58
Q

In Fas-FasL mediated apoptosis, in _______ cells such as thymocytes, caspase-8 can directly cleave _______ – independent of ________.

A

Type-I
Caspase-3
Mitochondria

59
Q

In Fas-FasL mediated apoptosis, in _______ cells such as virus-infected hepatocytes, caspase-8 cleaves ______ and this goes on to stimulate the release of ________ from mitochondria – mitochondria dependent.

A

Type-II
Bid
Cytochrome c

60
Q

In Fas-FasL mediated apoptosis, cytochrome c, together with ______ and ATP then activates ________ which in turn then activates _______.

A

Apaf-1 (apoptotic peptidase activating factor 1)
Caspase-9
Caspase-3

61
Q

In Fas-FasL mediated apoptosis, caspase-3 activates _____ via degradation of _____. Then, activated _____ causes DNA degradation in the nuclei.

A

CAD (caspase-activated DNase)
ICAD (inhibitor of CAD)
CAD

62
Q

In granzyme-mediated apoptosis, it involves specific TCR-dependent recognition and induction of apoptosis in target cells. TCR recognizes specific Ag within _______ molecules. This interaction brings CTL and target cell in close contact which results in the formation of the _______ _______.

A

Class I MHC

Immunologic synapse

63
Q

In granzyme-mediated apoptosis, the immunologic synapse ensures that normal bystander cells are not injured by CTLs reacting against infected cells. _______ and _______ are secreted into the synapse and perform the killing and cannot diffuse to other nearby cells. CTLs are not injured during the killing of targets.

A

Perforin

Granzymes

64
Q

There are granzymes ____, ____, and ____, which are _______ _______.

A

A
B
C
Serine proteases

65
Q

Granzyme ____ is the only one shown to be required for CTL cytotoxicity in vivo.

A

B

66
Q

In granzyme-mediated apoptosis, this is a membrane-perturbing molecule that is homologous to the C9 complement protein.

A

Perforin

67
Q

Perforin insertion into the target cell membrane elicits a compensatory membrane repair process in the target cell that leads to internalization of both the perforin and granzymes into ________.

A

Endosomes

68
Q

When in the target cells, granzyme B activates _______ which triggers apoptosis.

A

Caspase-3

69
Q

CD8+ T cells cooperate with CD4+ T cells and in defense against intracellular microbes. Intracellular bacteria such as L. monocytogenes are phagocytized by _________ and may survive in phagosomes and escape into the cytoplasm.

A

Macrophages

70
Q

CD4+ T cells respond to class II MHC-associated peptide Ag derived from bacteria and produce ______ and _____.

A

IFN-y

IL-2

71
Q

T/F. CD4+ T cells respond to class I MHC-associated peptides derived from cytosolic Ags and kill the infected cells.

A

False. CD8+ T cells respond to class I MHC-associated peptides derived from cytosolic Ags and kill the infected cells.