21.7: Immunology, Self, non-self discrimination Flashcards
What are the central (2) and peripheral (3) B cell tolerance mechanisms?
Central:
Deletion, anergy
Peripheral:
Ignorance/anergy/death
Is B or T cell tolerance more efficient?
T cell tolerance
What signals do we need for a mature B cell to respond/survive?
- Surface Ig-Ag interaction
2. T cell help (CD40L and CKs)
What happens if you lack CD40L?
Hyper IgM pathology
Where does T cell development occur?
Thymus:
Cortex (immature thyrocytes)
–>corticomedullary junction (tolerance)
–>medulla
What are the 2 T-cell checkpoints?
DP thymocytes: Positive selection (keeping the good)
Negative selection (getting rid of the bad, if TCR for self pMHC is high affinity)
What is AIRE and what is it important for?
AIRE (autoimmune regulator of expression): a transcription factor
Important to tolerise against antigens not normally expressed in the thymus.
What do defects in AIRE lead to?
Failure of negative selection, autoimmunity
What are the 2 signals needed for T-cell activation?
- TCR, MHC+peptide
2. Co-stimulation
What happens to T cells without co-stimulation?
Anergy and tolerance
Why is Treg important and what does it express?
Immunosupression and antiinflammatory cell, expresses TGFb and IL-10
What are the 2 types of Tregs? When do they occur?
nTregs (straight from thymus)
iTregs (naive CD4–>supressant)
What do iTregs express? What does this inhibit?
Express: CTLA4 inhibiting co-stimulation
What defects occur in a loss of:
central tolerance
peripheral tolerance
Central: AIRE defect
Peripheral: Foxp3 defect (loss of Treg)
What type of AID is Type 1 diabetes?
What HLA types does it occur more frequently in?
Organ specific, T cell mediated
HLA: DR3-DQ2, DR4-DQ8
