Self/Non-Self Discrimination

Question 1

Where is central tolerance generated for T and B cells?

Answer 1

T cells: thymus

B cells: bone marrow

Question 2

Where is peripheral tolerance generated?

Answer 2

Secondary lymphoid organs

Peripheral tissue

Question 3

List the 4 mechanisms used to induce tolerance

Answer 3

Deletion
Anergy
Ignorance
Regulation

Question 4

How is peripheral tolerance achieved for B cells?

Answer 4

Via ignorance/anergy/death due to lack of co-stimulation/T cell help

Question 5

Which is more efficient: B or T cell tolerance?

Answer 5

T cell

Question 6

What happens to a B cell that reacts with a multivalent self molecule in the bone marrow?

Answer 6

Undergoes clonal deletion or receptor editing, resulting in apoptosis

Question 7

What happens to a B cell that reacts with soluble self molecule in the bone marrow?

Answer 7

Migrates to the periphery where it becomes anergic due to low numbers of IgM receptors and high IgD

Question 8

What happens to a B cell that reacts with low-affinity non-cross-linking self molecule in the bone marrow?

Answer 8

Migrates to the periphery where it becomes a mature but clonally ignorant B cell (does not receive T cell help or Ag stimulation)

Question 9

What are the 3 signals required for a mature B cell to respond and survive?

Answer 9

Ig-Ag interaction
CD40-CD40L (T cell help)
Cytokines

Question 10

Does peripheral B cell tolerance occur pre- or post-somatic hypermutation?

Answer 10

Both

Question 11

How do the outcomes of B cell activation differ based on whether there is a low or high affinity interaction with the CD4 T cell?

Answer 11

Low affinity: short lived plasma cell (B cell eventually dies)
High affinity: transit to germinal centre, proliferation, isotype switching and affinity maturation to produce a memory B cell or plasma cell

Question 12

List the 5 stages of aB T cell development in the thymus

Answer 12

Early T-lineage precursor
Pro-T cell
Double negative thymocytes
Double positive thymocytes
Single positive T cell (either CD3+CD4+CD8- or CD3+CD4-CD8+)

Question 13

What are the 2 selection processes double positive thymocytes undergo following the expression of TCRs?

Answer 13

Positive selection

Negative selection

Question 14

What is positive selection in the context of T cell development?

Answer 14

Thymocytes that express TCRs capable of recognising self-MHC are selected to survive (others undergo death by neglect)

Question 15

What is negative selection in the context of T cell development?

Answer 15

Immature lymphocytes with strong reactivity to self-pMHC undergo apoptosis

Question 16

How is tolerance to tissue specific self Ags achieved?

Answer 16

Some tissue specific self Ags are expressed by thymic epithelial cells under the control of AIRE (autoimmune regulator of expression) transcription factor

Question 17

What is the result of mutations in AIRE?

Answer 17

Failure of negative selection for some Ags causing autoimmunity

Question 18

What are the 3 signals required for T cell activation?

Answer 18

TCR-pMHC
CD28-CD80/86
Cytokines

Question 19

What is the result if T cells do not receive co-stimulation via CD28-CD80/86 interactions?

Answer 19

Anergy (characterised by failure to proliferate, inactivation and tolerance)