Lecture 12 (Exam 2)

Question 1

Although T cell numbers remain more or less constant over the human lifespan, pronounced _____-associated changes occur in T cell composition (naive vs. memory T cell subsets).

Answer 1

Age

Question 2

It is well accepted that the functional naive T cell output decreases after puberty due to _______ _______, resulting in increased homeostatic proliferation of existing naive T cells and eventually phenotypic conversion of naive T cells into virtual memory cells.

Answer 2

Thymic involution

Question 3

In contrast to the shrinking naive compartment and its impaired ability to activate and differentiate with age, the proportion of memory T cells increases during early life, remains stable throughout adulthood, but starts to show ________ changes after about 65 years.

Answer 3

Senescent

Question 4

One of the most prominent T cell changes to occur with age is the loss of _____ expression and the progressive accumulation of highly differentiated ________ cells, mainly in the CD8+ T cell population.

Answer 4

CD28

CD28- T(EM)

Question 5

In immunosenescence of T cells, the cells are characterized by what?

Answer 5

1) Decreases proliferative capacity
2) Shortened telomeres
3) Reduced TCR repertoire
4) Enhanced cytotoxic activity

Question 6

Ag-activated T cells respond by producing ______ and expressing ______ receptors leading to cell proliferation. The result is expansion of the clone of T cells that are specific for the Ag.

Answer 6

IL-2

IL-2R

Question 7

Some of the progeny differentiate into (EFFECTOR/MEMORY) cells, which serve various functions in cell-mediated immunity, and (EFFECTOR/MEMORY) cells, which survive for long periods.

Answer 7

Effector

Memory

Question 8

Activated T cells does not produce cytokines randomly. Each subset of T helper cells tends to produce a set of particular cytokines which determine the phenotype. This process is called _________ or ________ of T helper cells.

Answer 8

Differentiation

Commitment

Question 9

The outcome of Th0 cell activation is generation of various T helper subsets —

• • _____ cells activate a cell-mediated immune response
• • _____ cells activate an Ab-mediated immune response
• • _____ cells involved in inflammation and anti-bacterial response
• • _____ cells - follicular helper T cells remain in the LN and help B cells

Answer 9

Th1
Th2
Th17
Tfh

Question 10

Th1, Th2, Th17, and Tfh cells are all ______ T helper cells.

Answer 10

CD4+

Question 11

IL-23 is a pro-inflammatory cytokine composed of _____ and _____ subunits. The _____ subunit is shared with IL-12. However, IL-23 and IL-12 have different receptors and different effects.

Answer 11

p19
p40
p40

Question 12

IL-12 produced by DCs and macrophages activate the transcription factors _____ and _____, and IFN-y produced by NK cells activates ______, which together stimulate the differentiation of naive CD4+ T cells into the _____ subset.

Answer 12

STAT4
T-bet
STAT1
Th1

Question 13

Th1 cells amplifies their response by producing _____, which inhibits the development of Th2 and Th17 cells.

Answer 13

IFN-y

Question 14

Th1 cells amplifies their response by producing _____, which inhibits the development of Th2 and Th17 cells.

Answer 14

IFN-y

Question 15

Th1 cells amplifies their response by producing _____, which inhibits the development of Th2 and Th17 cells.

Answer 15

IFN-y

Question 16

IL-4 produced by activated mast cells and eosinophils activates the transcription factors ______ and ______, which stimulate the differentiation of naive CD4+ T cells to the ______ subset.

Answer 16

GATA-3
STAT6
Th2

Question 17

______ produced by the Th2 cells amplifies this response and inhibits the development of Th1 and Th17 cells.

Answer 17

IL-4

Question 18

IL-1, IL-6, and TGF-B activate the transcription factors ______ and ______, which stimulates the differentiation of ______ subset.

Answer 18

RORyt
STAT3
Th17

Question 19

______ induced by RORyt and STAT3 amplifies generation of Th17 cells in an autocrine regulatory manner.

Answer 19

IL-21

Question 20

TGF-B may promote Th17 responses by suppressing _____ and _____ cells, both of which inhibit Th17 differentiation.

Answer 20

Th1

Th2

Question 21

______ is a very important cytokine in activation of Th17 cells.

Answer 21

IL-23

Question 22

______ produced by Th17 cells protect from extracellular pathogens and is involved in tissue inflammation and autoimmunity.

Answer 22

IL-17

Question 23

This is a process that eliminates T cells which would be non-functional due to an inability to bind MHC.

Answer 23

Death by neglect

Question 24

______ induces inflammation. Inflammation occurs at a high ratio of _____/_____.

Answer 24

IL-17

IL-17/IL-22

Question 25

______ controls homeostasis. Constitutive low ratio of ______/______.

Answer 25

IL-22 | IL-17/IL-22

Question 26

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

Answer 26

IL-15

Question 27

Nontraditional _____ T cells have been termed non-conventional innate-like T cells owing to several distinguishing features that are shared with innate immune cells.

Answer 27

y/d (gamma/delta)

Question 28

Another important feature of y/d T cells is their ______ for epithelial surfaces, such as those of the liver and skin, and mucosae from respiratory, digestive and reproductive organs.

Answer 28

Tropism

Question 29

Nontraditional y/d T cells recognize conserved non-peptide antigens that are unregulated by stressed cells which resemble _______ or _______ recognized by PRRs.

Answer 29

PAMPs | DAMPs

Question 30

Upon activation, y/d T cells rapidly produce ________ that regulate pathogen clearance, inflammation, and tissue homeostasis in response to tissue stress. These cells acquire a pre-activated phenotype associated with the up regulation of memory markers early in their development. This pre-activated status allows rapid induction of effector functions following the detection of tissue stress.

Answer 30

Cytokines

Question 31

The physiological roles fulfilled by y/d T cells are varied and include: -- Protective immunity against extracellular and intracellular ________ -- _______ surveillance -- Modulation of innate and adaptive immune responses -- Tissue healing and epithelial cell maintenance -- Regulation of physiological _______ function

Answer 31

Pathogens Tumor Organ

Question 32

Similar to BCRs and aB TCRs, y/d TCRs are generated through somatic rearrangement of _______, _______, and ______ gene segments.

Answer 32

V (variable) D (diversity) J (joining)

Question 33

The detection of stress-induced molecules by y/d T cells is achieved via using both TCR and non-TCR molecules (such as ______ and ______) that act separately, synergistically, or additively to activate particular y/d T cell effector functions.

Answer 33

TLRs (Toll-like receptors) | NKRs (Natural killer receptors)

Question 34

Non-traditional y/d T cells can recognize three sets of stress-induced stimuli. The first is -- -- MHC-related and -unrelated TCR ligands (such as the weakly polymorphic MHC class I-like human ______ molecules, microbial and endogenous phospho-antigens).

Answer 34

CD1c

Question 35

Non-traditional y/d T cells can recognize three sets of stress-induced stimuli. The second is -- -- Various cells surface molecules such as MHC class I polypeptide-related sequence A (MICA) that engage the activating ______ such as NK group 2, member D (NKG2D).

Answer 35

NKRs

Question 36

Non-traditional y/d T cells can recognize three sets of stress-induced stimuli. The third is -- -- ______ and/or ______ recognized by pattern recognition receptors (PRRs) such as TLRs and dectin 1.

Answer 36

DAMPs | PAMPs

Question 37

This is a recently discovered PRR that plays an important role in anti fungal innate immunity. It is a specific receptor for Beta-glucans. Beta-glucans are glucose polymers found in the cell walls of fungi, such as zymosan.

Answer 37

Dectin-1

Question 38

Non-traditional y/d T cells have y/d TCRs and identical (with aB T cells) ______.

Answer 38

CD3

Question 39

Most y/d T cells do not express ______ or ______ co-receptors.

Answer 39

CD4 | CD8

Question 40

Non-traditional y/d T cells are present where?

Answer 40

Intestine Uterus Tongue

Question 41

The y/d T cells develop largely in the _______, generating their defining receptor via RAG-mediated V(D)J recombination.

Answer 41

Thymus

Question 42

Functions of y/d T cells: - - First line of _______ - - __________ (function as regulatory cells) - - Bridging between _______ and _______ responses

Answer 42

Defense Immunoregulation Innate Adaptive

Question 43

The y/d T cells may be considered a component of (INNATE/ADAPTIVE) immunity due to rearrangement of TCR genes that occurs to produce junctional diversity. However, the repertoire y/d TCRs is much less diverse than aB TCRs.

Answer 43

Adaptive

Question 44

The y/d T cells may be considered part of the (INNATE/ADAPTIVE) immunity because a restricted TCR may be used as a patter recognition receptor (PRR). The y/d TCRs recognize unpresented Ags. Several y/d T cell subsets have a memory phenotype as a consequence of peripheral stimulation by environmental or stress-induced ligands.

Answer 44

Innate

Question 45

It has been postulated that _____ T cells kill cells that become stressed as the result of a microbial infection.

Answer 45

y/d

Question 46

______ cells are T lineage cells that share morphological and functional characteristics with both T cells and NK cells.

Answer 46

NKT (Natural killer T cells)

Question 47

(HIGH/LOW) numbers of NKT cells are found virtually everywhere -- T and NK cells are found in peripheral blood, spleen, liver, thymus, bone marrow, and lymph nodes.

Answer 47

Low

Question 48

In the liver, 30-50 percent of hepatic T cells are ______ cells.

Answer 48

NKT

Question 49

Following their activation, NKT cells can immediately commence ________ secretion without first having to differentiate into effector cells.

Answer 49

Cytokine

Question 50

The rapidity of their response makes NKT cells important players in the very first line of (INNATE/ADAPTIVE) defense against some types of bacterial and viral infections.

Answer 50

Innate

Question 51

In addition, many of the cytokines are secreted by NKT cells have powerful effects on a/B T cell differentiation and functions, linking NKT cells to (INNATE/ADAPTIVE) defense.

Answer 51

Adaptive

Question 52

NKT cells represent a heterogenous group of ______/______ T cells.

Answer 52

CD3+/CD56+

Question 53

NKT cells constitute only 0.2 percent of all peripheral _______ T cells. They express T cell markers such as TCR, CD40L, CD3, CD4, as well as some NK cell markers such as (CD56+).

Answer 53

Blood

Question 54

NKT cells express the Ag-specific TCR that is generated after VDJ recombination, but like innate immune cells, they do not develop immunological ________.

Answer 54

Memory

Question 55

NKT cells carry what is sometimes referred to as a "______-______" aB TCR because they express an invariant T cell receptor alpha chain.

Answer 55

Semi-invariant

Question 56

NKT cells recognize self- and foreign ______ and ______.

Answer 56

Lipids | Glycolipids

Question 57

In NKT cells, lipids and glycolipids should be presented within non-polymorphic ______ molecule -- Ag presenting complex like MHC.

Answer 57

CD1d

Question 58

Upon activation, NKT cells produce a diverse array of cytokines including...

Answer 58

``` IL-10 TGF-B Th1/Th2 cytokines IFN-y IL-4 GM-CSF ```

Question 59

Dysfunction or deficiency of NKT lead to...

Answer 59

Autoimmunity (diabetes or atherosclerosis) Cancers Asthma progression

Question 60

NKT cells recognition of glycolipid Ags presented by CD1d leads to a release of cytokines and expression of ______ that results in the activation of APCs and many other bystander cells.

Answer 60

CD40L

Question 61

In NKT cells, the diversity and extent of cytokine production can have a broad range of effects, ranging form enhanced cell-mediated immunity (_____ responses) to suppressed cell-mediated immunity and enhanced Ab-mediated immunity (_____ responses).

Answer 61

Th1 | Th2

Question 62

NKT cells can function within the ______ ______ via direct or indirect interactions with tumor cells.

Answer 62

Tumor microenvironment (TME)

Question 63

In the (DIRECT/INDIRECT) activation pathway, NKT cells recognize lipid-CD1d complexes on surface of tumor cells and then directly mediate killing of tumor cells. By making inflammatory cytokines like IFN-y, this also helps TME-resident NK cells perform their anti-tumor cell effector functions.

Answer 63

Direct

Question 64

In the (DIRECT/INDIRECT) activation pathway, NKT cells recognize lipid-CD1d complexes on the surface of TME-resident APCs or tissue-associated macrophages (TAMs). This interaction leads to NKT cell-mediated killing of immunosuppressive TAMs, leading to a less immunosuppressive environment where tumor-infiltrating NK cells can better perform their functions.

Answer 64

Indirect

Question 65

Alternately, if the CD1d is on the surface of a TME-resident APC, the NKT cell an activate that APC and stimulate production of ______, helping resident effector cells like NK cells overcome the immunosuppressive state of the tumor.

Answer 65

IL-12