T-Cell Mediated Immunity

Question 1

What are the locations of immature dendritic cells and mature dendritic cells?

Answer 1

• Immature: peripheral tissue looking for pathogen
• Mature: lymph nodes presenting antigen via MHC

Question 2

Why are dendritic cells confined to the cortex of lymph nodes after migrating from the periphery?

Answer 2

Because that is where naive T-cells congregate

Question 3

Are macrophages or dendritic cells the primary APNs?

Answer 3

Dendritic

Question 4

Dendritic cells are only capable of activating ______ cells

Answer 4

Naive CD8 T-cells

Question 5

What is the difference between receptor-mediated endocytosis and macropinocytosis?

Answer 5

• RME: Pathogen binds to receptor which triggers endocytosis
• MPC: endocytosis for pathogens too large to bind to receptor

Question 6

Why are there more restrictions on CD8 activation compared to CD4?

Answer 6

CD8 cells are the killer cells

Question 7

Identify where the dendritic cells are located based on their morphology

(MHCII = Green ; Lysosomal protein = Red)

Answer 7

Question 8

What dendritic cell surface receptor binds pathogen to activate said cell?

Answer 8

TLR

Question 9

What is the function of CCR7 on the surface of dendritic cells?

Answer 9

• Binds to chemokine CCL21
• Causes dendritic cells to exit the lymph and make their way toward the periphery

Question 10

Which lymphocyte is the most abundant in blood vessels?

Answer 10

Naive T cells

Question 11

Describe the two modes of entry for T-cells into lymph nodes.

Answer 11

1. From the blood via high endothelial venules (HEVs)
2. From the lymphatics via afferent lymphatic vessels

Question 12

Each naive T cell recirculates from blood through a lymph node and back to blood every ______.

Answer 12

12-24 hours

Question 13

What are quiescent T-cells?

Answer 13

• Small, undividing, unactivated T-cells
• Have condensed chromatin, little cytoplasm, and little RNA/protein synthesis

Question 14

What is “homing” in regard to T-cell migration?

Answer 14

Process by which T-cells leave the bloodstream and enter the T-cell zone of lymph nodes

Question 15

Which cytokines secreted by stromal cells and dendritic cells guide T-cell homing? (2)

Answer 15

• CCL21
• CCL19

Question 16

Which cell surface protein of T-cells binds CD34 and GlyCAM-1 on HEVs to facilitate attachment to endothelial cells.

Answer 16

L-selectin

Question 17

LFA-1 on T-cells binds to _______ on HEVs to strengthen attachment to endothelial cells.

Answer 17

ICAM-1 and ICAM2

Question 18

ICAM-1 and ICAM-2 on dendritic cells bind to _____ on T-cells

Answer 18

LFA-1

Question 19

ICAM3 on the surface of T-cells binds to _____ on dendritic cells.

Answer 19

DC-SIGN

Question 20

CD2 on the surface of T-cells binds _____ on dendritic cells to increase adhesion

Answer 20

LFA-3

Question 21

What is the function of sphingosine 1-phosphate (S1P)?

Answer 21

• Guide T-cells out of the lymph node if they don’t encounter antigen
• Via gradient in the medulla

Question 22

Activated T-cells express _____ to sequester S1P receptors back into themselves

Answer 22

CD69

Question 23

Explain the events that IMMEDIATELY occur when a naive T-cell recognizes a peptide:MHC complex? (not an enzymatic cascade)

Answer 23

• LFA-1 / ICAM interactions are strengthened by conformational changes
• T-cells proliferate (clonal expansion)
• Dendritic cells maintain contact with clones as a “nursery” for propagation of T-cells

Question 24

What is the function of CD28 on the T-cell surface?

Answer 24

Bind to B7 on dendritic cell to act as a co-stimulator when TCR binds MHC.

Question 25

What are the two complexes that form the synapse between T-cells and dendritic cells?

Answer 25

* c-SMAC - central supramolecular activation complex * P-SMAC - peripheral supramolecular activation complex

Question 26

TCR/MHC activation induces phosphorylation of _____ and \_\_\_\_\_.

Answer 26

* CD3 cytoplasmic tails * ζ chain

Question 27

What are ITAMs?

Answer 27

* Immunoreceptor tyrosine-based activation motifs * tyrosine residues that allow for phosphorylation (specifically for CD3 and the ζ chain)

Question 28

What is the function of Lck in T-cell activation?

Answer 28

* Tyrosine kinase * Phosphorylates CD3 and ζ chain ITAMs, as well as ZAP-70

Question 29

What is the function of ZAP-70?

Answer 29

* Binds phosphorylated tyrosines of the ζ chain * Necessary for initiating the major T-cell signaling pathway

Question 30

ZAP70 initiates activation of various transcription factors that induce T-cell proliferation, differentiation, and effector function. Which transcription factors are they? (3)

Answer 30

1. NFAT 2. NF-κB 3. AP-1

Question 31

NFAT, NF-κB, and AP-1 activation ultimately lead to the activation of \_\_\_\_\_, a growth cytokine critical for T-cell activation.

Answer 31

IL-2

Question 32

Name the immunosuppressive drugs that target IL-2 (3).

Answer 32

1. Cyclosporin A 2. Tacrolimus (FK506) 3. Rapamycin

Question 33

True or false. Self-antigen is not expressed in the thymus.

Answer 33

True

Question 34

Absence of CD28 in T-cells results in \_\_\_\_\_

Answer 34

* Anergy * Will not respond to external stimuli

Question 35

What happens to a T-cell that recognizes self-antigen?

Answer 35

Anergy

Question 36

What are the functions of the following helper T-cells? 1. T_H1 2. T_H17 3. T_H2 4. T_FH 5. T_reg

Answer 36

1. T_H1 - activation of macrophages 2. T_H17 - enhance neutrophil response 3. T_H2 - Activate cellular antibody response to parasites 4. T_FH - Activate B cells; maturation of antibody response 5. T_reg - Supppress other effector T cells

Question 37

What are the master regulators (or defining transcription factors) of the following helper T cells? 1. T_H1 2. T_H17 3. T_H2 4. T_FH 5. T_reg

Answer 37

1. T_H1 - T-bet 2. T_H17 - RORγT 3. T_H2 - GATA3 4. T_FH - Bcl6 5. T_reg - FoxP3

Question 38

Which of the following types of helper T cells remains in the secondary lymph tissue? 1. T_H1 2. T_H17 3. T_H2 4. T_FH 5. T_reg

Answer 38

T_FH

Question 39

Activated T-cells no longer express L-selectin. What is the consequence of this?

Answer 39

They can no longer enter secondary lymph tissue

Question 40

VLA-4 is only expressed by activated T-cells, allowing them to leave blood and enter tissues by binding to _____ expressed on endothelial cells of infected tissue.

Answer 40

VCAM-1

Question 41

True or false. Only CD4 T-cells can produce cytotoxins.

Answer 41

False. Only CD8 T-cells can

Question 42

What is the function of IFN-γ produced by CD8 T-cells?

Answer 42

* Inhibition of viral replication in infected cells * Increases processing of viral antigen and presentation * Activation of local macrophages

Question 43

What is the function of perforin, granulysin, and serglycin?

Answer 43

* Make a pore on target cell * Deliver granzymes

Question 44

What is the function of granzymes?

Answer 44

It is a serine protease that initiates cascade of proteolytic cleavage and activation of nucleases to induce apoptosis of infected cells

Question 45

What proteins are present in the p-SMAC region of the dendritic-T cell synapse?

Answer 45

1. LFA-1 2. ICAM-1 3. Talin

Question 46

What proteins are present in the c-SMAC region of the dendritic-T cell synapse?

Answer 46

1. TCR 2. CD2 3. CD4 4. CD8 5. CD28 6. PKC-θ