activation of T lymphocytes

Question 1

naive T cells transiently ___ with many DCs and stop when they find ___ Ag for their TCR

Answer 1

interact

specific

Question 2

The T cells are activated to differeneitate into effector cells. Then activated T cells may:

1. remain in the lymphoid organs to help:
2. migrate to sites of infection to help:

Answer 2

1. B lymphocytes
2. activate macrophages

Question 3

phases of T cell responses:

1. Ag recognition by T cells induces ___ secretion resulting in clonal expansion as a result of cell proliferation and differentiation of the T cells into effector or memory cells
2. the effector CD4 T cells response to Ags by producing cytokines that have several actions, such as the recruitment and activation of leukocytes and ____ of B cells
3. the effecotor CD8 CTLs function by ____ infected and altered host cells

Answer 3

1. IL-2
2. activation
3. killing

Question 4

generally, T cells only recognize ____ ____ ____ Ag presented via ____

Answer 4

linear protein peptide

MHC

Question 5

naive T cells are only activated by _____

effector T cells can respond to Ag presented by ____ and ____

Answer 5

DCs

B cells and macrophages

Question 6

the proliferation of T lymphocytes and their differentation into effector and memory cells requires 3 signals

1.

2.

3.

Answer 6

1. Ag recognition
2. costimulation
3. cytokines

Question 7

superantigens:

1. activates ____ T cells without the presence of Ag or other stimulatory factors
2. bind MCH II on APC variable ___ subunit of the TCR; NOT the ___ ___ ___
3. casuses massive proliferation and production of ____ cytokines

Answer 7

1. CD4
2. beta subunit of the TCR; NOT the peptide binding groove
3. proinflammatory

Question 8

mitogen

Answer 8

peptide or small protein that induces a cell to being cell division: mitosis

e.x. - superantigen

Question 9

proliferation and differentation of T cells - Signal 1 (Ag recognition):

1. TCR recognizing and binds to MHC complex on ____
2. CD4/CD8 complex containing ____ phosphorylate ____ on ____ chains
3. ____ binds to p-ITAMs and LCK activates ZAP-70 via phosphorylation
4. ZAP-70 phosphorylates ____ and ____ which act as scaffolding for proteins
5. actives the MAPK, RAS, and PLC-gamma pathway

(not a strong enough stimulation)

Answer 9

1. DCs
2. LCK ITAMs zeta
3. ZAP-70
4. LAT and SLP-76

Question 10

proliferation and differenation of T cells - Signal 2 - Costimulation:

1. ____ on naive cells wil bind to the ____ on the DC
2. activation of the pathways that lead to ____ , ____ , cyclins, and differentiation factors
3. upregulation of ____ and other CD28-like receptors (these are inhibitory receptors that will compete for binding with the CD80/86) to regulate the immune response

(unactivated DCs express low levels of these costimulatory molecules, while activated DCs express high levels)

Answer 10

1. CD28 CD80/86 (B7)
2. survival factors (Bcl-2) , proliferation factors (IL-2)
3. CTLA-4

Question 11

microbes and cytokines produced during innate immune responses (inflammation) activate DCs to express ____ , such as CD80/86 molecules

Answer 11

costimulators

Question 12

activated DCs produce cytokines such as ____ which stimulate the ____ of naive T cells into effector cells

Answer 12

IL-12

differentiation

Question 13

TCR-signaling alone produces a strong activation of ____ but only weak activation of ____ and ____

Answer 13

NFAT

NF-kB and AP-1

Question 14

costimulation induces ____ and ____

Answer 14

NFkB and AP-1

Question 15

the expression of ____ co stimulators is regulated and ensures that T lymphocyte responses are initiated only when needed

Answer 15

B7 (CD80/86)

Question 16

CTLA-4 will bind to ____ on activated cells to prevent the further overativation of T cells

Answer 16

CD80/86 (B7)

Question 17

CTLA-4 is not expressed on the surface of

Answer 17

naive and memory cells

(is stored in intracellular vesicles

Question 18

major function of PD-1 is

Answer 18

the programmed cell death of T cells following inflammaotry immune responses

Question 19

the stronger the stimulation through the TCR (and CD28) the ____ the amount of CTLA-4 that is dposited on the T cell surface

Answer 19

greater

Question 20

PD-1 downregulates the activity of T cells and thus limits ____ ____ damage in response to a microorganism infection in that tissue

Answer 20

collateral tissue

Question 21

PD-1 is upregulated by

Answer 21

IFN-gamma

Question 22

excessive induction of PD-1 on T cells can induce an ____ state in T cells

Answer 22

anergic

Question 23

proliferation and differentation of T cells - Signal 3 (cytokines-differentiation):

cytokines in the environment will determine what effector T cell is produced

1. IL-12 → ____ → ____ → ____
2. IL-4 → ____ → ____ → ____
3. IL-6 → ____ → ____ → ____
4. TFG-beta → ____ → ____ → ____

Answer 23

1. IL-12 → STAT4 → T-bet → Th1 cell
2. IL-4 → STAT6 → GATA3 → Th2
3. IL-6 → STAT3 → RORgammat → Th17
4. TFG-beta → SMAD2-SMAD4 → FOXP3 → Treg

Question 24

changes in protein expression:

1. recognition of the ____ to its antigen
2. upreguation of the ____ transcription product
3. ____ production and release
4. ____ expression (reduces surface expression of S1PR1)
5. ____ expression
6. ____ expression
7. cell division (growth and ____)

Answer 24

1. TCR
2. c-Fos
3. IL-2
4. CD69 (retention in lymph nodes)
5. IL-2Ralpha (proliferation)(increases affinity of IL-2 receptors)
6. CD40L (activation of DCs, macrophages, T/B cells)
7. proliferation

Question 25

IL-2 stimulates the ____ , ____ , ____ of Ag-activated T cells

Answer 25

survival, proliferation, and differentiation

Question 26

_characteristics of IL-2:_ 1. IL-2 induces the anti-apoptotic protein \_\_\_\_ 2. stimulates cell cycle progression by degrdation of the cell cyle inhibitor \_\_\_\_ 3. is required for the survival and function of ____ cells

Answer 26

1. Bcl-2 2. p27 3. Treg

Question 27

_decline and resolution of the T cell response:_ 1. elimination of Ag leads to ____ of the T cell response 2. this leads to decrease in ____ produced 3. lack of IL-2 leads to decrease in ____ which leads to intrinsic apoptosis 4. inhibitory receptors ____ and ____ lead to cell death 5. ____ cells can regulate the survival of the remaining T cells

Answer 27

1. contraction 2. IL-2 3. Bcl-2 4. CTLA-4 and PD-1 5. Treg

Question 28

linear model of T cell differentiation

Answer 28

T cells differentiate → most effector cells die → a few survive and become memory cells (most accepted)

Question 29

branched theory of memory T cell differentiation

Answer 29

effector and memory cells are alternative fates of activated T cells (T cells differentiate into either memory cells or effector cells)

Question 30

\_\_\_\_ TF promotes the generation of memory cells

Answer 30

Blimp-1

Question 31

memory T cells constitute the most ____ lymphocyte population in the body during the lifetime

Answer 31

abundant

Question 32

the vast majority of memory T cells reside in ____ site

Answer 32

tissue (including lymphoid tissue, intestine, lungs, and skin)

Question 33

the ____ TF drives differentation of effector cells in CD4 T cells

Answer 33

T-bet

Question 34

_resident memory T cells_ (T_RM) 1. produce ____ and \_\_\_\_ 2. are specific for pathogens and other Ags that have been encountered previously through that ____ epithelium 3. remain at ____ sites

Answer 34

1. IFN-gamma and TNF 2. barrier 3. tissue

Question 35

_central memory T cells_ (T_CM): 1. express ____ and \_\_\_\_ 2. home mainly to ____ , ____ and circulate in the blood

Answer 35

1. CCR7 and L-selectin 2. LNs, spleen

Question 36

_effector memory T cells_ (T_EM) : 1. do not ____ but produce IFN-gamma and TNF or become \_\_\_\_ 2. upon entering the tissue can become ____ cells and reside in epithelial barrier tissues at the interface between the host and the environment 3. circulate in \_\_\_\_

Answer 36

1. proliferate cytotoxic 2. T_RM 3. blood

Question 37

_properties of memory cells:_ 1. can survive in a quiescent state without \_\_\_\_ 2. respond to repeated exposure ____ and with a great response (naive T cells: 5-7 days ; memory T cells: 1-3 days) 3. the number of memory T cells specific for any Ag is ____ than the number of niave T cells specific for the same Ag 4. undergo slow ____ process leading to longer life span 5. maintenance requires ____ but not antigens 6. environmental ____ and ____ cytokines induce the expression of anti-apoptotic proteins and stimulate low-level proliferation

Answer 37

1. Ag 2. faster 3. greater 4. self-renewing 5. cytokines 5. IL-7 and IL-15

Question 38

markers of memory T cells

Answer 38

IL-7R, CD45, and CD27

Question 39

functional naive T cell output decreases after puberty due to thymic ____ , resulting in increased homeostatic proliferation of existing naive T cells and eventually phenotypic conversion of naive T cells into virtual memory cells

Answer 39

involution

Question 40

in contrast to the shrinking naive compartment and its impaired ability to activate and differenetiate with age, the proportion of memory T cells increases during early life, remains stable throughout adulthood, but starts to show senescent changes after about ____ years

Answer 40

65

Question 41

one of the most prominent T cell changes to occur with age is the loss of ____ expression and the progressive accumulation of hightly differentiated CD28^- T_EM cells, mainly in the CD8 T cell population

Answer 41

CD28