Flashcards in Autoimmunity Deck (63)
What is the range of autoimmune disorders?
➝ organ specific
What are 2 examples of an organ specific autoimmune disease?
➝ Graves disease
➝ Type 1 diabetes
What is Graves disease?
➝ an antibody response to the TSH receptors in the thyroid
Why do you get bulging eyes in Graves disease?
➝ Low level of TSH receptors in the fibroblasts in the eye
➝ immune deposition of antibodies in the eye
What are the 6 types of HLA B27- associated spondyloarthropathies?
➝ Ankylosing spondylitis
➝ undifferentiated spondyloarthropathy
➝ reactive arthritis
➝ psoriatic arthritis
What is usually associated with HLA B27- associated spondyloarthropathy?
➝ bowel inflammation
What is the cause of systemic lupus erythematous (SLE)?
➝ Autoantibodies to nuclear antigens :
➝ double stranded DNA
What are the 8 signs of SLE?
➝ discoid lesions
➝ butterfly rash
➝ mucus membrane ulceration
What is autoimmunity?
➝ Failure of the regulatory controls in the immune system that prevent it attacking itself
What is central tolerance?
➝ Destroy self-reactive T or B cells before they enter the circulation
What is peripheral tolerance?
➝ Destroy or control any self reactive T or B cells which do enter the circulation
How does central tolerance of B cells occur?
➝ 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?
➝ 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?
➝ 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?
➝ T cells that don't bind to any MHC - death by neglect
➝ T cells that bind to MHC too strongly - apoptosis triggered- negative selection
➝ 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?
➝ A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissue
What is AIRE and what is its function?
➝ (autoimmune regulator)
➝ it promotes self tolerance by allowing the thymic expression of genes from other tissues
What do mutations in AIRE result in?
➝ multi organ autoimmunity
What are the three steps in peripheral tolerance?
Why does the ignorance step happen in peripheral tolerance?
➝ the antigen may be present in too low a concentration to reach the threshold for T cell receptor triggering
➝ e.g immunologically privileged sites such as the eye or the brain
➝ T cells will not come across the antigen
What is anergy?
➝ Exposure to antigen without appropriate co-stimulatory signals
How does anergy occur?
➝ Naive T cells needs co-stimulatory signals to be activated
➝ most cells lack co-stimulatory proteins and MHC class II
➝ if a naive T cell sees its MHC/peptide without appropriate co-stimulation it becomes anergic
What does anergic mean?
➝ 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?
➝ Treg cells
How do Treg cells work?
➝ 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
What two conditions cause a varying of Treg numbers?
➝ Cancer - increased Treg
➝ autoimmune - decreased Treg
What do Treg cells express?
➝ Transcription factor FOXP3
What do mutations in FOXP3 lead to?
➝ IPEX disease
➝ immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome
On what chromosome is MHC located?
➝ chromosome 6