T cells

Question 1

What are CCR7 and L-selectin receptors for?

Answer 1

They are attracted to lymph nodes and lead naïve T cells to lymph nodes

Question 2

What is the S1P gradient for?

Answer 2

Leads activated T cells to traffic out of the lymph nodes (to infection site)

*Downregulation of CCR7 and L-selectin also play a role in this

Question 3

What is LFA-1?

Answer 3

A cell adhesion molecule.
As T cell bind with APC,
TCR signals LFA-1. Initially low-affinity LFA-1:ICAM-1 interactions.
Conformational change in LFA-1 increases affinity and prolongs cell-cell contact.

Question 4

What are the 3 signals required for the activation of naive T cells?

Answer 4

Signal 1: TCR binding to peptide-MHC
Signal 2: Co-stimulation (B7 molecule one APC bind to CD28 T-cell protein)
Signal 3: Cytokines (regulate the differentiation of CD4+ T cells)

Question 5

What are the effects of T cell activation?

Answer 5

Increased expression of CTLA-4, an inhibitory receptor for B7 molecules.
Increased expression of IL-2 receptor and secrete IL-2, IL-2 binds to its own receptor. IL-2 induces T cell proliferation, which allows clonal expansion.

Question 6

What are the similarities and differences between CTLA-4 and CD28?

Answer 6

Similarities
- Expressed by T cells
- Binds to B7 on ap sites

Differences
- Not constitutively expressed on T cells, expression is induced 2-3 days following T cell activation
- CTLA-4 much higher affinity for B7 than CD28
- CTLA-4 delivers negative signalling to T cells

CTLA-4 competes with CD28 for binding to B7 → Decreased IL-2 production, reduced T cell proliferation

Question 7

What does the T cell receptor CD3 complex do?

Answer 7

Able to transduce intracellular signal which the TCR is unable to

Question 8

What do CD8+ T cells do?

Answer 8

Cytotoxic effector proteins that trigger apoptosis are contained in the granules of CD8+ cytotoxic T cells which are released at site of cell contact.
Cytotoxic T cells kill target cells bearing specific antigen while sparing neighbouring uninfected cells.

Question 9

What cytokines do Th1 and Th2 cells release respectively?

Answer 9

Th1: IFN-gamma
Th2: IL-4, IL-13

Question 10

What do CD4+ Th1 cells do?

Answer 10

They activate macrophages to become highly microbicidal.

Question 11

What do CD4+ Th2 cells do?

Answer 11

They act on B cells to
stimulate production
mainly of IgE
antibodies.

Question 12

How do CD4+ T cells help CD8+ T cells?

Answer 12

CD4+ T cells produce IL-2 to promote CD8+ T cell proliferation (direct)
CD4+ T cells can further activate APCs to better activate CD8+ T cell (indirect)

Question 13

What do Th17 cells do?

Answer 13

Th17 cells produce the cytokine IL-17, which induces production of
chemokines and other cytokines from various cells, and these recruit
neutrophils (and monocytes) into the site of inflammation

Question 14

How are T cells selected in the thymus?

Answer 14

Based on the strength of TCR interaction with self peptide-self MHC. Both TCR-peptide and TCR-MHC contacts are required to stabilise interaction.

Absent or minimal -> ignorance
Low to moderate -> positive selection
Strong -> negative selection

Question 15

What are the mechanisms of peripheral tolerance?

Answer 15

Ignorance, anergy, deletion, Treg cell

Question 16

Are anergised T cells able to respond when they receive adequate costimulatory signals?

Answer 16

No

Question 17

What do Treg cells do?

Answer 17

Tregs are IL-2-dependent T cells, which possess TCRs that recognise self peptide-self MHC strongly, and act on self-reactive immune cells to suppress their activity
Treg cells constitutively express CTLA-4 to inhibit T cell activation.

Question 18

What is PD-1?

Answer 18

Expression: Induced after T cell activation; strongly expressed in chronically activated T cells
Effect: Inhibits activation signals from the TCR complex and CD28
Negatively regulates effector T cell function during chronic antigen stimulation, “immune checkpoint”
- Limits T cell mediated tissue damage during chronic / persistent infections
- Inhibits autoreactive T cells

Question 19

What is the autoimmune regulator (AIRE)?

Answer 19

Causes transient expression in the thymus of extra-thymic tissue-specific antigens
Allows for negative selection of TCRs specific for self antigens that are normally not expressed in the thymus
Autoimmune diseases are associated with a mutation in AIRE.