Tolerance, autoimmunity and autoimmune disease Flashcards
Define tolerance?
failure of the immune system to respond to a particular antigen
How do dizygotic cattle twins become tolerant to each other?
- share placental circulation
- exposed to each other’s alloantigens in utero
- become tolerant to these alloantigens
- do not reject tissue grafts from one another
Bovine viral diarrhoea virus tolerance?
- calves exposed to viral antigens in utero become tolerised to the virus
- so in life there is no immune response to it
- are born with the infection and become persistently infected
What is High zone adult tolerance?
A single high dose of antigen can induce tolerance in both T and B cells
What is Low zone adult tolerance?
- repeated injections of low dose antigen
- induces T-cell tolerance
- T cells more readily tolerised than B cells
- if antigen is T-dependent, B cells are effectively tolerant anyway
- remember that a lot of B cell activity is T cell dependent, and so by tolerating the T cells you also tolerise B cells
How is oral tolerance induced?
- foreign antigen is fed to a human or animal
- when the same antigen is injected systemically then the individual will fail to respond
How can oral tolerance be of advantage?
- can use as a therapy to switch off autoimmune reactive responses
- systemic immune responses are suppressed by feeding the antigen
- oral delivery of autoantigens or allergens may have therapeutic application
What is Self tolerance?
- failure of the immune system to recognise self antigens (A GOOD THING)
- T and B cells are ‘educated’ to render them tolerant to self
- breakdown of self tolerance = autoimmunity = bad
What is Central tolerance?
- cells that bind to “self” cells are deleted in thymus
- Treg cells monitor autoreactive cells to have them destroyed
How do T cells become autoreactive?
- A small number of self reactive T cells can escape and hence are self intolerant
- Various mechanisms that prevent these self reactive T cells from doing any damage
- Called peripheral tolerance
- Recognition of self peptide by autoreactive T cells is done in absence of signal 2 and 3
Peripheral tolerance maintained by - Treg cells which suppress these autoimmune responses
How may B cells come to be self tolerant?
- immature B cells encounter self antigen in bone marrow
- negative selection process
- apoptosis of autoreactive clones
- cannot activate without T-cell help
What is Autoimmunity?
failure of self tolerance resulting in activation of autoreactive cells which may produce pathology and disease
Name some autoimmune diseases in companion animals
- IMHA
- IMTP
- IMNP
- pemphigus
- polyarthiritis
- myasthenia gravis
- thyroiditis
- diabetes mellitus
- systemic lupus
What 5 factors are associated with autoimmunity?
- immunological abnormalities
- genetic background
- age
- gender
- environmental triggers
What can a loss of self tolerance be caused by?
lack of regulatory cells
