Autoimmune Disease Flashcards
Outline autoimmunity
- Against self-antigen
- Caused by loss of tolerance and may or may not cause disease
- Can be organ-specific (Type I diabetes targets pancreas β cells which produce insulin) or systemic (RA)
Outline the importance of Tregs in autoimmunity
Carry FOXP3 receptors
• Treg deficient humans develop IPEX syndrome- mutations in Foxp3 gene
-> aggressive autoimmunity and early death
-> onset within first months of birth
-> ~80% IPEX patients have Type I diabetes
Which genes are linked to autoimmune disease?
• Ankylosing spondylitis: HLA-B27- risk of developing is 90 times higher
• certain polymorphism increase risk:
PTPN22- RA, others- T/B cell receptor signal strength control
CTLA4- RA,T1D- impaired Treg function
CD25- MS,T1D- abnormal Treg function
C2,C4- systemic lupus erythematosus SLE
What can cause autoimmunity?
Genes
Environment
Failed regulation
How can infection cause autoimmunity?
When a peptide from a microbe resembles a self antigen (molecular mimicry)
Why is autoimmunity more common in women?
Immune genes on X chromosome-> gene dosage effects
- females have more CD4 T cells and higher levels of circulating antibody
- sex hormones impact microbiome
Outline autoantibodies
- blocking of receptor (Myasthenia gravis- Ab blocks AChR) Type II HS
- stimulating receptor (Graves’ disease- Ab stimulates TSHR- release of thyroid hormones) Type V HS
- act as opsonins- facilitate phagocytosis as Fc bound by phagocytes (autoimmune cytopenias- haemolytic anaemia (RBCs))
Outline T cell mediated autoimmunity
- MS- T cell driven attack of CNS: CD4 T cells infiltrate CNS, activate macrophages, B cells-> demyelination
- T1D- T cell driven attack of insulin-producing beta cells in Islets of Langerhans in pancreas
- SLE- multifactorial systemic autoimmune disease: autoantibodies against nuclear components, immune complex deposition
What are the mechanisms of autoimmunity?
Autoantibodies
T cell mediated
