Production of Effector T-cells

What is the immunological synapse?

Contact between T-cells and antigen presenting cells or target cells

Involves co-stimulators, adhesion receptors

APC-T-cell initial scanning involves multiple of which molecule?

Adhesion molecules

T-cells initially bind APC through low-affinity LFA and ICAM interactions. What makes this a high-affinity binding?

TCR binding to MHC-peptides. Which induces LFA-1 to under a conformational change to have higher affinity

Which two signals are required for initial activation of naive T-cells?

1. TCR peptide MHC/CD4 or CD8

2. Co-stimulatory binding of CD28 on T-cell to B7 ligand on APC

What is signal 3?

Differentiation signals from APCs for the naive T-cells. They are CYTOKINES

Why is it important that both signals are given to the naive T-cell?

Avoiding autoimmunity

Which signal is more important?

TCR-peptide/MHC

Will there be an effect if you only get the CD28-B7 signal?

Nope

What induces expression of B7 ligands?

TLR signals. But they also increase adhesion molecules on T-cells, and induce chemokine/cytokine production

What kinds of antigens do dendritic cells present?

Peptides

Viral antigens

Allergens

What kinds of antigens do macrophages present?

Particulate antigens

Intracellular and extracellular pathogens

What kinds of antigens do B cells present?

Soluble antigens

Toxins

Viruses

What does IL-2 do?

Trigger T-cell proliferation

Acts as a growth regulator

Which signal helps produce IL-2 as a co-stimulator?

CD28-B7

Stabilizes mRNA for IL-2 and increases its transcription

What happens to its IL-2 receptor when a T-cell is activated?

Becomes high-affinity, and secretes IL-2

Signals itself to induce T-cell proliferation

Do resting and naive T-cells have CTLA-4?

No

After T-cell proliferation, what is induced?

Negative regulators of co-stimulation

What does CTLA-4 do?

It’s a competitive inhibitor of CD28, which binds with a higher affinity to B7 ligands

Limits proliferation and makes T-cell go from proliferative stage → effector stage

What’s the difference between a naive and effector T-cell?

Effectors license cells to kill or help to activate immunity quickly

Do effector T-cells need co-stimulation to act?

No. Only signal 1