Flashcards in Self/Non-Self Discrimination Deck (19):
Where is central tolerance generated for T and B cells?
T cells: thymus
B cells: bone marrow
Where is peripheral tolerance generated?
Secondary lymphoid organs
List the 4 mechanisms used to induce tolerance
How is peripheral tolerance achieved for B cells?
Via ignorance/anergy/death due to lack of co-stimulation/T cell help
Which is more efficient: B or T cell tolerance?
What happens to a B cell that reacts with a multivalent self molecule in the bone marrow?
Undergoes clonal deletion or receptor editing, resulting in apoptosis
What happens to a B cell that reacts with soluble self molecule in the bone marrow?
Migrates to the periphery where it becomes anergic due to low numbers of IgM receptors and high IgD
What happens to a B cell that reacts with low-affinity non-cross-linking self molecule in the bone marrow?
Migrates to the periphery where it becomes a mature but clonally ignorant B cell (does not receive T cell help or Ag stimulation)
What are the 3 signals required for a mature B cell to respond and survive?
CD40-CD40L (T cell help)
Does peripheral B cell tolerance occur pre- or post-somatic hypermutation?
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?
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
List the 5 stages of aB T cell development in the thymus
Early T-lineage precursor
Double negative thymocytes
Double positive thymocytes
Single positive T cell (either CD3+CD4+CD8- or CD3+CD4-CD8+)
What are the 2 selection processes double positive thymocytes undergo following the expression of TCRs?
What is positive selection in the context of T cell development?
Thymocytes that express TCRs capable of recognising self-MHC are selected to survive (others undergo death by neglect)
What is negative selection in the context of T cell development?
Immature lymphocytes with strong reactivity to self-pMHC undergo apoptosis
How is tolerance to tissue specific self Ags achieved?
Some tissue specific self Ags are expressed by thymic epithelial cells under the control of AIRE (autoimmune regulator of expression) transcription factor
What is the result of mutations in AIRE?
Failure of negative selection for some Ags causing autoimmunity
What are the 3 signals required for T cell activation?