Immunology: Central and peripheral tolerance Flashcards
What is tolerance?
Tolerance is the failure of the adaptive immune system to respond to an antigen
Tolerance is essential in prevention of autoimmunity where the immune system attacks its own cells (“self”)
What is central tolerance?
selection of T and B cells which only react with “non-self” antigens in the thymus and bone marrow respectively
What is peripheral tolerance?
T and B cells in the secondary lymphoid tissues (peripheral lymphoid tissues) require further education and regulation
Where does central tolerance occur?
Central tolerance occurs in the thymus (T cells) and bone marrow (B cells). These areas are viewed as central in immunological terms.
What is neonatal tolerance?
Occurs in fetus or neonate
If fetal thymus is exposed to non-self antigens before it’s mature / immunocompetant, then the animal becomes tolerant to those antigens
Fetal calf infection with BVDV results in a persistently (silently) infected animal, which then infects other cattle
What is oral tolerance?
Prevents response to dietary proteins / gut microflora (while preserving protective immune responses to GI pathogens!)
Failure results in hypersensitivity disease (food allergy, IBD)
How does central tolerance in bone marrow (B cells)?
BCR+ cells that interact with self antigens on stromal cells are deleted by apoptosis).
Mature “educated” B lymphocytes move to populate secondary lymphoid organs (adaptive immune response repertoire)
How do T cells use anergy to become tolerant in the periphery?
Anergy (failure to react to specific antigen)
T cells fail to receive appropriate co-stimulatory signals for activation
Failure of T cell activation leads to cytokine deficiency, so B cells also become anergic
How else can T cells become tolerant in the periphery?
Immunological ignorance: Immune privileged sites (testis, brain, eye, kidney etc)
Antigen presenting cell failure: Processes “self” antigen but fails to present
How do Tregs aid in peripheral tolerance?
Dampen down the immune response
Regulatory T cells (Treg) inhibit Th1 and Th2 cell function via production of inhibitory cytokines (TGF-β and or IL-10) or direct cell / cell contact
What are the three subtypes of Treg?
Three types known (all are CD4+ cells which express CD25 to a greater or lesser extent):
• Natural Tregs cells (nTreg)
• T regulatory cells, subset 1 (Treg1)
• T helper 3 cells (Th3)
Activation of nTregs causes large amounts of IL-10 to be produced, what does this do?
It has immunosuppressant properties on the activity of both Th1 and Th2 cells. Inhibition of Th2 cells then inhibits B cell activity and antibody production
What does cell to cell contact between APC and nTreg cause?
upregulating CTLA-4 which ligates B7 but does not cause activation (inhibitory receptor)
How can we induce tolerance in practice?
Administration of selected allergens at a low dose (with alum adjuvant)
• Intradermal injection
• Sublingual administration
How does the mare not react to her foal and become tolerant to it?
Local immunosuppression …. Evidence for Tregs and split immunological tolerance (local immune tolerance / suppression vs peripheral activity)
