T Lymphocyte Activation and Differentiation

Question 1

What is the initiating event of adaptive immunity?

Answer 1

The interaction between naive T cells and APCs

Question 2

List the 4 events of the innate immune system that occurs before adaptive immunity is initiated.

Answer 2

1. APCs activated via PRRs
2. APCs engulf pathogen
3. APCs process and present antigen-derived peptide bound to MHC class molecule
4. APCs are activated and migrate to secondary lymphoid organs

Question 3

In the thymus, T-cells underwent which types of selection?

Answer 3

Positive selection - MHC restriction
Negative selection - self tolerance

Question 4

In order to activate T-cells and commit them to a lineage what 3 signals are needed?

Answer 4

1. TCR rearrangement
2. Costimulatory molecule interaction
3. Cytokine production

Question 5

Activation of naive T-cells results in…

Answer 5

generation of effector and memory T-cells

Question 6

Explain TCR engagement.

Answer 6

1. Begins with activation of tyrosine kinase Lck
2. TCR engages MHC-peptide, coreceptor CD4 or CD8 stabilizes it
3. Lck phosphorylates ITAMs on CD3
4. becomes docking site and signals cascades

Question 7

Explain Costimulation.

Answer 7

• costimulatory receptor CD28 binds to CD80/CD86 ligand to activate naive T cells
• costimulatory receptor CTLA-4 binds to CD80/CD86 for negative regulation of the immune response

Question 8

What happens in positive costimulation?

Answer 8

1. CD28 expressed on surface of T cells
   - enhances TCR engagement
   - binds CD80/CD86
2. ICOS is expressed on memory and effector T cells
   - binds ICOSL on activated APCs

Question 9

What happens in negative costimulation?

Answer 9

1. CTLA-4 induced after a day of activation
   - binds CD80/CD86
   - shuts down signaling pathway
2. PD-1
   - binds PD-L1/PD-L2
   - mediate T-cell tolerance, program death

Question 10

T/F. In APCs, the expression of costimulatory molecules is activated.

Answer 10

True

Question 11

Explain IL-2 function.

Answer 11

Autocrine cytokine
- transcription of IL-2 binds to CD25 (IL-2R)
- causes T cell proliferation

Question 12

What is the function of polarizing cytokines?

Answer 12

• differentiate T helper (CD4+) subsets
• APCs bind to PAMPs and induce cytokine secretion

Question 13

Cytokine signaling is activated by? phosphorylated by?

Answer 13

Activated by: JAK
Phosphorylated by: JAK on STAT transcription factors

Question 14

Effector T helper subsets are distinguished by?

Answer 14

1. Polarizing cytokines from APCs recognizing PAMPs via PRRs ….turn on
2. A master gene regulator that activates …. a transcription factor
3. Signature set of effector cytokines (differentiation)

Question 15

List the effector T helper subset Th1 effector cytokines and the function.

Answer 15

Th1: regulate immunity to intracellular bacteria and viruses
- IFNγ, TNF
- activates macrophages for apoptosis, inflammation

Question 16

List the effector T helper subset Th2 effector cytokines and the function.

Answer 16

Th2: regulate immunity to extracellular parasitic infections
- IL-4, IL-5, IL-13
- activates eosinophils, allergy

Question 17

List the effector T helper subset Th17 effector cytokines and the function.

Answer 17

Th17: regulate immunity to extracellular bacteria and fungi
- IL-17A/F, IL-22
- autoimmunity, inflammation

Question 18

List the effector T helper subset Treg effector cytokines and the function.

Answer 18

Treg: inhibits immune response and autoimmunity
- IL-10
- inhibitory

Question 19

List the effector T helper subset Tfh effector cytokines and the function.

Answer 19

Tfh: regulates humoral immunity
- IL-4, IL-21
- in spleen, B cells

Question 20

List all the effector T cell subsets.

Answer 20