Define immune tolerance
The failure of the adaptive immune system to respond to an antigen
(it is essential in the prevention of autoimmunity where the immune system attacks its own cells)
Describe the 2 forms of tolerance
- Central: selection of T/B cells which only react to non-self antigens. Occurs in thymus and bone marrow.
- Peripheral: occurs in secondary lymphoid tissue. T/ B cells undergo further education/ regulation
What are the types of immune tolerance?
- Self tolerance (central)
- Neonatal (central)
- Adult (peripheral)
- Oral (peripheral)
What is meant by positive/ negative T cell selection?
- Occurs in thymus
- Positive: Selects T cells that bind to self MHC molecules
- Negative: deletes T cells that react STRONGLY with self peptide/ antigen or self MHC
- Means most of the T ells that survive only activate if a non-self peptide is presented by a self MHC molecule.
How are B cells educated in the bone marrow?
- BCR+ cells thats interact with self antigens are deleted by apoptosis
- Mature B lymphocytes then move onto secondary lymphoid organs
Are most antigens T or B cell dependant?
T cell
- induction of T cell tolerance will lead to B cell tolerance
Why is peripheral tolerance important?
- Many antigens are not presented to T cells whilst in the thymus, these cells may activate and immune response to the novel antigens if not controlled.
- Some T cells that react to self peptide escape the thymus and so must be controlled during peripheral tolerance to prevent autoimmune responses.
What are the mechanisms by which T cells become tolerant/ unresponsive in periphery?
- Anergy
- Immunological ignorance
- Antigen presenting cell failure
- T regulatory cells (Tregs)
Explain the process of anergy
- The failure to react to specific antigens
- TCR engages MHC and antigen
- Cytokines that upregulated co-stimulatory molecules are absent
- T cell isn’t activated and cannot undergo clonal expansion so becomes apoptotic and dies.
Describe regulatory T cells
- Inhibit Th1 and Th2 cell function via production of inhibitory cytokines (TGF-B and IL-10) or direct cell-cell contact
- 3 types:
Natural Tregs
T regulatory cells (Treg1)
T helper 3 cells (Th3)
What is the role of nTreg cells?
- Inhibit immune responses
- Their activation causes large concentration of IL-10 to be produced
- IL-10 is immunosuppressant on the activity of both Th1 and 2.
- Inhibition of Th2 leads to inhibition of B cell activity/ AB production
What happens if immune tolerance fails?
- Allergic (abnormal) IR to environmental antigens
- Autoimmunity develops
What is hyposensitisation/ immunotherapy?
- Administration of selected allergens and low dose with alum adjuvant
- Intradermnal injection
- Sublingual administration
Describe adult peripheral tolerance during pregnancy
- Local immunosuppresion- evidence for Tregs and split immunlogical tolerance
