Autoimmunity Flashcards
List some examples of Organ-specific autoimmune diseases
- Graves disease - TSH receptors in the thyroid
- Type 1 diabetes - insulin-producing cells of the pancreas
What is HLA B27-associated spondyloarthropathes
- Ankylosing spondylitis, undifferentiated spondyloarthropathy, reactive arthritis, psoriatic arthritis, urethritis, iritis
- Spectrum of severity and HLA B27 association
- Associated with bowel inflammation
Describe Systemic lupus erythematosus (SLE)
- Multi-system disease
- characterised by autoantibodies to nuclear antigens eg double stranded DNA
- Relapse and remission
What is autoimmunity
- The immune system has various regulatory controls to prevent it from attacking self proteins and cells
- Failure of these controls will result in immune attack of host components – known as autoimmunity.
What is the idea of immune tolerance
The immune system does not attack self proteins or cell - It is just tolerant to them
What are the 2 types of tolerance
- Central tolerance – destroy self-reactive T or B cells before they enter the circulation
- Peripheral tolerance – destroy or control any self reactive T or B cells which do enter the circulation
How are T cells selected for MHC binding
- Need to select for T cell receptors which are capable of binding
self MHC - If binding to self MHC is too weak, may not be enough to allow signalling when binding to MHC with foreign peptides bound in groove
- If binding to self MHC is too strong, may allow signalling irrespective of whether self or foreign peptide is bound in groove
- Undergoes negative selection in thymus gland
How does a T cell encounter MHC from all over the body
A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissues (AIRE)
How does Autoimmune Regulator work
- Promotes self tolerance by allowing
the thymic expression of genes from
other tissues - Mutations in AIRE result in multi-organ
autoimmunity
What are the 3 areas of peripheral tolerance
- Ignorance
- Anergy
- Regulation
What is the Ignorance phase of peripheral tolerance
- Antigen may be present in too low a concentration to reach
the threshold for T cell receptor triggering - Immunologically privileged sites e.g. eye, brain
What is the Anergy phase of peripheral tolerance
- Naive T cells need costimulatory signals in order to become activated
- Most cells lack costimulatory proteins and MHC class II
- If a naive T cell sees it’s MHC/peptide ligand without appropriate costimulatory protein it becomes anergic
What is the tolerance phase of peripheral tolerance
- A subset of helper T cells known as Treg (T regulatory cells) inhibit other T cells
- Defective Treg observed in multiple sclerosis
How can endocrine factors also be cause for autoimmune diseases
- SLE is >10 times more common in females than males
- MS is approximately 10 times more common in females than males
- Diabetes is equally common in females and males
- Ankylosing spondylitis is approximately 3 times more common in males than females
How can environmental factors be a cause for autoimmunity
- Hygiene hypothesis: NOD mice and
SPF conditions. Migration and T1D, MS and SLE - Smoking and rheumatoid arthritis
- 13 pairs of identical twins where 1 of each pair smoked and 1 of each pair had RA
- In 12/13 cases the twin with RA was the smoker
