Flashcards in W21-L6: Self, Non-self discrimination Deck (23):
What is B cell Central Tolerance?
What is B cell Peripheral Tolerance?
Need 2 signals for the mature B cell to respond and survive
• Ignorance/Anergy/death (Lack of co-stimulation/T cell help)
B cell tolerance is more efficient than T cell tolerance
Where does T cell development occur?
Double positive (DP) thymocytes undergo which selection processes following the expression of a TCR?
1. Positive selection-thymocytes that express TCRs capable of recognising self-MHC are selected to survive
2. Negative selection–removal of immature lymphocytes that have strong reactivity to self peptide
What controls expression of tissue specific antigens?
What do defects in AIRE lead to?
failure of negative selection for some antigens, and result in autoimmunity
What is T cell central tolerance?
Involves immature/developing lymphocytes and occurs in primary lymphoid organs
• Selection of Tregs
What is T peripheral central tolerance?
Involves mature lymphocytes and occurs in secondary lymphoid organs, and peripheral tissues
What two signals are required for activating naive T cells?
1. TCR-peptide MHC interactions
Without co-stimulation, T cells become...
What are iTregs?
derived following activation of naïve CD4 T cells in the presence of TGF ß
What do iTregs secrete and express?
Secrete immunosuppressive cytokines - IL-10 and TGF ß, Express CTLA4 and inhibit co-stimulation
How does CTALA4 work?
Binds B7 on APC more avidly than CD 28 on niave T cells and delivers inhibitory signals to activated T cells
What are 3 key components of autoimmunity?
1. Genetic susceptibility
3. Loss of self-tolerance
What are the two types of autoimmune disease?
1. Organ-specific: Confined to particular organs or cell types and the
antigens recognized are organ specific
2. Systemic: Multiple tissues of the body are targeted and the antigens recognized are more ubiquitous
What are some diseases related to B cell autoimmunity?
1. Graves disease (stimulating Ab)
2. Myasthenia Gravis (inhibitory Ab)
3. SLE (immune complex deposition)
What are some diseases related to T cell autoimmunity?
1. Insulin dependent diabetes mellitus (IDDM)
2. Multiple sclerosis (MS)
Type 1 insulin dependent diabetes mellitus is characterised by?
autoimmune destruction of pancreatic β-cells, characterised by infiltration of lymphocytes, weak autoantibody response, T cell reactivity to islet proteins
What genes are more frequently found in Type 1 insulin dependent diabetes mellitus?
HLA DR3-DQ2 and DR4-DQ8
Multiple Sclerosis is characterised by?
CD4 T cells specific for myelin antigens promote an inflammatory response and degrade the myelin sheaths covering nerve axons
Which genes are associated with multiple sclerosis?
HLA-DR15 and HLA-DQ6