Autoimmunity Flashcards
What is the range of autoimmune disorders?
β systemic
β organ specific
What are 2 examples of an organ specific autoimmune disease?
β Graves disease
β Type 1 diabetes
What is Graves disease?
β an antibody response to the TSH receptors in the thyroid
Why do you get bulging eyes in Graves disease?
β Low level of TSH receptors in the fibroblasts in the eye
β immune deposition of antibodies in the eye
What are the 6 types of HLA B27- associated spondyloarthropathies?
β Ankylosing spondylitis β undifferentiated spondyloarthropathy β reactive arthritis β psoriatic arthritis β urethritis β iritis
What is usually associated with HLA B27- associated spondyloarthropathy?
β bowel inflammation
What is the cause of systemic lupus erythematous (SLE)?
β Autoantibodies to nuclear antigens :
β double stranded DNA
What are the 8 signs of SLE?
β discoid lesions β alopecia β butterfly rash β pericarditis β arthritis β proteinuria βRaynauds β mucus membrane ulceration
What is autoimmunity?
β Failure of the regulatory controls in the immune system that prevent it attacking itself
What is central tolerance?
β Destroy self-reactive T or B cells before they enter the circulation
What is peripheral tolerance?
β Destroy or control any self reactive T or B cells which do enter the circulation
How does central tolerance of B cells occur?
β Immature B cells in bone marrow encounter an antigen in a form which can cross-link their IgM then apoptosis is triggered
What happens if a T cell binds to MHC too weakly?
β it may not be enough to allow signalling when foreign peptides are in the groove
What happens if a T cell binds to MHC too strongly?
β it may allow signalling irrespective of whether self or foreign peptide is in the groove
What types of T cells get selected in the thymus and which get destroyed?
β T cells that donβt bind to any MHC - death by neglect
β T cells that bind to MHC too strongly - apoptosis triggered- negative selection
β T cells that bind self MHC weakly - signal to survive
How do T cells in the thymus encounter MHC bearing peptides from other parts of the body?
β A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissue
What is AIRE and what is its function?
β (autoimmune regulator)
β it promotes self tolerance by allowing the thymic expression of genes from other tissues
What do mutations in AIRE result in?
β multi organ autoimmunity
What are the three steps in peripheral tolerance?
β Ignorance
β anergy
β regulation
Why does the ignorance step happen in peripheral tolerance?
β the antigen may be present in too low a concentration to reach the threshold for T cell receptor triggering
β e.g immunologically privileged sites such as the eye or the brain
β T cells will not come across the antigen
What is anergy?
β Exposure to antigen without appropriate co-stimulatory signals
How does anergy occur?
β Naive T cells needs co-stimulatory signals to be activated
β most cells lack co-stimulatory proteins and MHC class II
β if a naive T cell sees its MHC/peptide without appropriate co-stimulation it becomes anergic
What does anergic mean?
β less likely to be stimulated in the future even if co-stimulation is present
What cells are involved in the regulation step in peripheral tolerance?
β Treg cells
How do Treg cells work?
β The Treg cells bind to an antigen on an APC they can send a negative signal to any other cells that are recognising antigens on that cell via TGF beta and IL-10
