Lecture 28 Flashcards
Define self tolerance
A state in which an individuals immune system does ot attack the normal tissues of the body
How is self tolerance built?
During lymphocyte development, potentially self-reactive T and B cells are identified and deleted (central tolerance)
Some self reactive cells escape elimination
Tolerance induced in mature lymphocytes that have left the central lymphoid organs is peripheral tolerance
What does ‘rescue by receptor editing’ mean? When does it occur?
Rescue by receptor editing is the continued expression of recombinase activating genes (RAG) which can allow cells to continue light chain rearrangement leading to alteration of specificity.
Occurs when a B cell is self reacting
What is the function of autoimmune regulator protein in the thymus?
AIRE creates a peripheral shadow in the thymus. This means it reflects any protein thats expressed in the body within the thymus.
What are 4 methods of peripheral tolerance?
- anergy- no secondary signal, not enough stimulus to get the T cell going
- Tregs- can be induced in the periphery due to specific cytokines from T cells to get rid of self-recognising Tcells
- Functional deviation (autoreactive T cells-> induced T regs)
- Activation induced cell death
What are 3 ways to induce tolerance?
- very large doses of antigen
- regulatory t cells
- oral antigen (tolerance towards food)
What is an example of a disease caused by the breakdown of central tolerance?
Autoimmune polyendocrinopathy-candidiases-ectodermal dysrophy (APECED)
What is an example of a disease caused by the breakdown of peripheral tolerance?
Multiple sclerosis
What are the symptoms of APECED?
Failure of multiple endocrine glands
Chronic mucocutaneous candadiasis
Ectodermal symptoms e.g. pitted nails, alopecia, vitiligo
What is the cause of APECED?
A deficiency in the AIRE protein. This means that the ‘peripheral shadow’ is not working in the thymus. So tissue reactive T cells aren’t getting screened for tissue specific proteins. This means that they escape central tolerance and are able to run wild in the body.
Why do people with APECED have chronic mucucutaneous candidasis?
Because it is associated with autoimmunity against the cytokine IL-17. Th17 cells are important for protection against fungi at epithelial surfaces. Therefore APECED can lead to immunodeficiency through autoimmunity to IL-17.
What causes multiple sclerosis?
An immune response against brain antigens such as myelin basic protein. Means that neurons can’t fire properly so signals dont get to the body properly.
What are symptoms of multiple sclerosis?
Muscle weakness, blindless, paralysis
How does the MS treatment Fingolimod work?
It prevents the movement of T and B cells from secondary lymphoid organs, preventing cells from entering the blood and tissues (including the CNS). This seems like it would cause heaps of other infections but there are tissue specific memory T cells to get rid of infections.
How does Type I interferon work as a therapeutic for multiple schlerosis?
Type 1 IFN binds to the APC which causes the activation of T reg cells. Tregs release IL-10 which downregulates Th17 cells. Th17 cells are the cells causing damage to the CNS.
