T Cell-Mediated Immunity

Question 1

1st phase of T cell response: Ag recognition

Answer 1

Ag recognition of T cells induces IL-2 secretions followed by clonal expansion of T cells, and differentiation into effector and memory cells.

Question 2

How do effector CD4+ cells respond to binding Ags?

Answer 2

They produce cytokines that regulate the recruitment and activation of leukocytes and activation of B cells.

Question 3

How do effector CD8+ cells respond to binding Ags?

Answer 3

They kill infected host cells.

Question 4

How does the number of effector T cells change once the Ag is eliminated?

Answer 4

The number of effector T cells is greatly reduced, but the memory cells remain in high quantity.

Question 5

3 required signals for proliferation and differentiation of T cells:

Answer 5

Ag recognition
Costimulation
Cytokines

Question 6

Activation of T cells requires recognition of Ag by:

Answer 6

Only DCs.

Question 7

Effector T cells can recognize Ags presented by:

Answer 7

Tissue macrophages and B cells.

Question 8

CD28:CTLA4

Answer 8

Inhibitory signal. Costimulation.

Question 9

CD28:CD80/86

Answer 9

Activating signal. Costimulation.

Question 10

LFA1:ICAM1

Answer 10

Adhesion w/ APCs.

Question 11

ITAMs

Answer 11

The region of signaling proteins that are phosphorylated on Tyr residues and become docking sites for tyrosine kinases.

Question 12

ITIMs

Answer 12

The region of signaling proteins that are sites for tyrosine phosphatases that counteract the action of ITAMs.

Question 13

Superantigens

Answer 13

Bind to MHC II molecules and the V region of beta subunit of the TCR. This causes the T cell and APC to stick together and continuously produce TNF, IL-1, and IL-2, which can lead to shock.

Question 14

Staphylococcus enterotoxins are:

Answer 14

Bacterial SAgs that cause food poisoning and TSS.

Question 15

DCs’ costimulation mechanism

Answer 15

Usually DCs do not express a high enough quantity of costimulation molecules. However, once the T cell binds the Ag on an APC, it releases cytokines which activate DCs to express the costimulatory molecules.

Question 16

CD28 binds to:

Answer 16

B7-1 (CD80) and B7-2 (CD86) on activated APCs.

Question 17

CTLA4 regulation

Answer 17

Naive and memory T cells have high levels of CD28, but little CTLA4. After the TCR is triggered by the Ag, CTLA4 is transported to the cell surface.

Question 18

The stronger the stimulation through the TCR (and CD28):

Answer 18

The greater the amount of CTLA4 deposited on the T cell surface. Therefore, CTLA4 functions as a signal dampener.

Question 19

Programmed cell death protein 1 (PD1) function

Answer 19

Regulate inflammatory responses in tissues by effector T cells recognizing Ag in peripheral tissues.

Question 20

PD1L

Answer 20

Downregulates activity of T cells and limits collateral damage in response to infection.
The best signal for PDL1 induction is INF-gamma.

Question 21

Excessive induction of PD1 causes:

Answer 21

An anergic state in T cells.

Question 22

IL-12 causes:

Answer 22

Activation of signaling molecule STAT4 that leads to expression of T-bet, which facilitates the generation of Th1.

Question 23

IL-4 causes:

Answer 23

Activation of STAT6 that leads to expression of GATA3 which facilitates the generation of Th2.

Question 24

IL-6 causes:

Answer 24

Activation of STAT3 that leads to expression of RORyt which facilitates the generation of Th17 cells.

Question 25

IGF-beta causes:

Answer 25

Activation of signaling molecule SMAD2-SMAD4 that promotes expression of FOXP3 and generation of T regulatory cells.

Question 26

Costimulatory molecules in CTLs

Answer 26

CD28-CD80

Question 27

T-bet regulates:

Answer 27

Transcription of genes coding for perforin, granzymes, annd IFN-gamma.

Question 28

Initiation of TCR signaling

Answer 28

ITAMs on zeta chains are phosphorylated.
Phosphorylated ITAMs bind ZAP-70 via the SH2 domains.
ZAP-70 is phosphorylated by Lck and activates ZAP-70 catalytic activity.
Activated ZAP-70 phosphorylates LAT and SLP-76, which functions as a scaffold to recruit other signaling molecules.
Phosphorylated LAT recuits GADS and GRB2, which phosporylates PLC1.

Question 29

PLC1 mechanism

Answer 29

PLC1 produces IP3 and DAG.
IP3 leads to increase in cytosolic Ca2+ and NFAT activation.
DAG activates both PKC which activates NF-kB.
DAG also actiavtes Ras that activates MAPK pathways and AP-1.

Question 30

IL-2 induces the:

Answer 30

Anti-apoptotic protein Bcl-2.

Question 31

IL-2 stimulates the cell cycle by:

Answer 31

Degredation of p27 (cell cycle inhibitor).

Question 32

IL-2 is required for the survival and function of what cells?

Answer 32

Treg cells.

Question 33

Changes in CD69 expression after T cell activation:

Answer 33

CD69 binds CD69L and reduces surface expression of S1PR1. This causes activated T cells to remain in the LNs long enough to receive signals that initiate the proliferation/differentiation into effector and memory cells.
After cells division, CD69 expression decreases.

Question 34

Actvated T cells express how much S1PR1?

Answer 34

High levels, so they can leave the LN.

Question 35

Expression of CD40L in activated T cells

Answer 35

T cells recognize Ag causing expresion of CD40L.
CD40L binds to CD40 on DCs, which leads to DC expression of B7, which causes secretion of cytokines,
Activated DCs stimulate T cell proliferation and differentiation.

Question 36

IL-2 starvation triggers:

Answer 36

The mitochondrial intrinsic pathway of apoptosis.

Question 37

Regulatory mechanisms contributing to normal contraction of immune responses (3):

Answer 37

CTLA4 and PD-1 (inhibitory receptors)
Apoptosis induced by TNFRI and Fas
Inhibition by Treg cell products

Question 38

T-bet drives differentiation of:

Blimp-1 drives proliferation of:

Answer 38

CD4+ T cells.

Memory cells.

Question 39

Memory T cells are generated from effector T cells via:

Answer 39

Epigenetic modifications.

Question 40

Naive T cells respond in __________, while memory T cells respond in __________.

Answer 40

5-7 days

1-3 days

Question 41

IL-7 and IL-15 induce the expression of:

Answer 41

Anti-apoptotic proteins and stimulate low-level proliferation.

Question 42

Central memory T cells

Answer 42

Home mainly to spleen and LNs and circulate in the blood.

They are capable of proliferation.

Question 43

Effector memory T cells

Answer 43

Circulate in blood.

Cannot proliferate, but secrete IFN-gamma and TNF or become cytotoxic.

Question 44

Resident tissue memory T cells

Answer 44

Reside in the epithelial barrier.
Produce IFN-gamma and TNF and are specific for Ags that have been previously encountered through that barrier epithelium.