Lecture 13 (Exam 2)

Question 1

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

Answer 1

CD8+

Question 2

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

Answer 2

DCs

Question 3

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

Answer 3

CTLs (Cytotoxic T lymphocytes)

Question 4

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.

Answer 4

CTLs

Question 5

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

Answer 5

CD28-CD80

Question 6

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

Answer 6

Lysosomes
Perforin
Granzymes

Question 7

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

Answer 7

IFN-y

Question 8

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

Answer 8

T-bet

Question 9

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

Answer 9

Perforin
Granzymes
IFN-y

Question 10

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

Answer 10

DCs

Question 11

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

Answer 11

class II MHC
class I MHC

Question 12

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.

Answer 12

CD4+ helper

Question 13

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).

Answer 13

Precedes
Education
Licensing

Question 14

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.

Answer 14

CD40L/CD40

IFN-y

Question 15

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

Answer 15

CD40L

CD40

Question 16

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.

Answer 16

CD80/CD86

Question 17

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

Answer 17

IL-15

Question 18

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

Answer 18

APCs

CTL

Question 19

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 ______.

Answer 19

IL-15R

IL-21R

Question 20

_____ 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.

Answer 20

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

Question 21

_____ 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.

Answer 21

IL-15

Question 22

_____ 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.

Answer 22

IL-21

Question 23

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

Answer 23

IL-2

Question 24

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

Answer 24

Autocrine loop

Question 25

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.

Answer 25

Alpha subunit

Question 26

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

Answer 26

Paracrine

Question 27

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.

Answer 27

IFN-y

Question 28

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

Answer 28

Macrophages

Question 29

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.

Answer 29

Class I MHC | Class II MHC

Question 30

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

Answer 30

IgG | IgE

Question 31

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.

Answer 31

IL-12

Question 32

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

Answer 32

IFN-y | TNF-B

Question 33

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.

Answer 33

True

Question 34

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

Answer 34

IL-12

Question 35

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.

Answer 35

IL-15

Question 36

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

Answer 36

CTLs

Question 37

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

Answer 37

Th1

Question 38

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

Answer 38

Chemoattractant

Question 39

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

Answer 39

True

Question 40

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

Answer 40

IFN-y

Question 41

______ 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.

Answer 41

IL-21

Question 42

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

Answer 42

Plasma | T follicular

Question 43

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

Answer 43

IL-21

Question 44

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

Answer 44

Th17

Question 45

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

Answer 45

Tumors

Question 46

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.

Answer 46

Inhibitors

Question 47

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

Answer 47

CD8+ | CTLs

Question 48

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.

Answer 48

TNF-B IFN-y Perforin Granzymes

Question 49

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

Answer 49

Effector

Question 50

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.

Answer 50

Exhaustion

Question 51

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

Answer 51

IFN-y | PD-1

Question 52

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

Answer 52

CTLs

Question 53

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

Answer 53

HIV | Hep C

Question 54

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

Answer 54

Tumors

Question 55

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.

Answer 55

FasL | Fas

Question 56

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.

Answer 56

CTL

Question 57

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

Answer 57

Procaspase-8 FADD Caspase-8 ***Study Lecture 13 Slide 35***

Question 58

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

Answer 58

Type-I Caspase-3 Mitochondria

Question 59

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.

Answer 59

Type-II Bid Cytochrome c

Question 60

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

Answer 60

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

Question 61

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

Answer 61

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

Question 62

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 _______ _______.

Answer 62

Class I MHC | Immunologic synapse

Question 63

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.

Answer 63

Perforin | Granzymes

Question 64

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

Answer 64

A B C Serine proteases

Question 65

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

Answer 65

B

Question 66

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

Answer 66

Perforin

Question 67

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 ________.

Answer 67

Endosomes

Question 68

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

Answer 68

Caspase-3

Question 69

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.

Answer 69

Macrophages

Question 70

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

Answer 70

IFN-y | IL-2

Question 71

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

Answer 71

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