RA/SLE Flashcards
What is SLE
Type III hypersensitivity. Skin rash caused by complexes of DNA and anti-DNA antibodies localised in the skin to cause inflammation due to triggering of complement. Capillaires of face near to surface which cause butterfly rash.
Gender bias - 10:1 female to male
What are the clinical features of SLE
Any organ/tissue
Skin (diverse patterns, photosensitivity, alopecia)
Joints (non-erosive arthritis and tendinitis)
Sicca symptoms (salivary, lacrimal, genital tract)
Glomerulonephritis (several patterns: mesangial, membranous and peripheral)
Neurological: CNS, eye, PNS
What is rheumatoid factor
non-specific and non-pathogenic. Antibody against the Fc portion of IgG. Present in sera many months before disease is apparent. Diagnostic factors of SLE.
What is the mechanism of antibody injury
Direct cytotoxicity (and clearance) e.g. autoimmune haemolytic anaemia, thrombocytopenia
Immune complex formation and deposition e.g. skin rashes and glomerulonephritis
Trigger pro-inflammatory response in cells carrying Fc gamma receptors (any cells that have receptors for tail end of IgG, e.g. neutrophils and macrophages)
Promote NK cell activation and/or cytotoxicity
What is RA
Type II, III and IV hypersensitivity reactions
Mediated by antibodies and immune cells
Swollen inflamed synovial membrane
Affects 1-2% of population Female: male 3:1 Crippling disease Killing disease High social costs: divorce and loss work Costs £3-4 billion annually to UK
What happens to synoviocytes in RA
Synoviocytes proliferate rapidly and thickens. Similar to tumour, uncontrolled growth. This is a pannus.
What do osteoclasts do in RA
Secrete enzymes to destroy underlying bone
What happens to the immune system in SLE
Very low circulating levels of complement. Excess production of alpha-IFN: a state of pseudo-viral infection. DNA/RNA not packaged and disposed of correctly activates TLRs (7/9). Activation of neutrophils.
What do B cells do in SLE
B cell turns into plasma cell to produce autoantibodies. Nuclear antigens form complexes. Tail end of IgG activates neutrophils and macrophages. B cell needs T cell help to make antibodies.
What are the genetic components of RA
HLA-DR1/HLA-DR4 (HLA-DR4 positively associated with more severe disease )
Common epitope QKRAA
Single nucleotide polymorphisms e.g. PTPN22
What happens to the synovial membrane in RA
Thickening of the synovial lining layer
Proliferation of fibroblast-like synoviocytes
Angiogenesis (physiological process through which new blood vessels from pre-existing vessels)
Influx of mononuclear cells ( T and B cells and monocytes)
Production of cytokines, chemokines and matrix metalloproteinases
