immunology : rheumatoid arthritis and SLE Flashcards
(28 cards)
what type of hypersensitivity is SLE
type 3 , complexes of dna and anti dna antibodies becoming localised causing inflammation in skin and can be all organs and tissues!
what is the prevalence of sle Europeans to afro carib, gender and age
more common in afro-carrib, gender bias females 10 times more likely and in females normally in 30s/40s
Name some clinical features of sle
• Any organ/tissue
• Common patterns
– 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, peripheral nervous system
what is the main issue that triggers off sle
abnormal apoptosis which exposes nuclear antigens, which act as damps activate innate response
list the antibodies formed when abnormal apoptosis occurs
Antinuclear autoantibodies – (ANA): multiple components • Anti-dsDNA • Anti-histone • Antibodies to extractable nuclear antigens (ENA) – Anti-Ro/Anti-La (RNA processing) – Anti-RNP/Anti-Sm (spliceosome) • Rheumatoid factor • Anti-cardiolipin antibodies
how do the antibodies cause injury in sle
direct cytoxicity e.g autoimmune haemolytic anemia and thrombocytopenia,
immune complex forms and deposits in the skin or the kidney tissues
Trigger pro-inflammatory response in cells carrying Fc
gamma receptors
• Promote NK cell activation and/or cytotoxicity
why in SLE is there an excess alpha IFN production
because the complexes fool the immune system into thinking there is a viral infection. (psuedo viral) a ifn is response to this
Immune system in sle
neutrophil activate, alpha ifn increase and complement consumption increases
what does abatacept do in sle
blocks cd86 and cd 26 by acting as ctla-4. so no second signal no activation
what hypersensitivities does RA involve
2,3,4
What is diff between ra and osteoarthritis
RA is inflammation around joint with bone erosion, osteoarthritis is wear and tear.
who does ra affect more men or women
females more 3 to one
what’s the aetiology of RA
Systemic autoimmune disease of unknown aetiology
describe why RA is a chronic inflammatory condition and what you can observe in inflamed joint
extensive angiogenisis, b and t cells (type iv), hyperplasic synovial lining, macrophages, dendrites, osteoblasts and fibroblasts
what do fibroblast and macrophages produce
chemokines to attract more cells to joints ccl2 ccl5 il8
cytokine tnf, il1,il6
MMP-1, -3 and -9(enzymes metalloproteinases eats collagen etc)
comment on gene predisposal to RA
hla dr1/hladr4, responsible for antigen presentation to t cell, genetic risk no more than 15%
What are risk factors(enviromental) for RA
smoking, infections such as ebv
what is a marker for RA not rheumatoid factor, that also has a great specificity for RA
Anti-citrullinated protein antibody
cyclic citrullinated peptide (CCP)
May predict erosive disease
what evidence supports involvement of t cells in RA pathogenisis
associations of RA with HLA DR1/4, ra and hiv together makes ra better because less cd4 t cells. il2 activates RA, synovial histology and synovial t cells activation and cytokines
In RA what happens to synovial membrane
Thickening of the synovial lining layer – proliferation of fibroblast-like synoviocytes • Angiogenesis • Influx of mononuclear cells (T and B cells and monocytes) • Production of cytokines, chemokines and matrix metalloproteinases
Direct cell contact between activated T cells and
monocytes induces
IL-1β production
Direct cell contact between T cells and FLS induces
MMP
production
• Direct cell contact between T cells and FLS induces
MCP1 production
• Main autoantibody associated with RA
rheumatoid factor-Non-specific and non-pathogenic
• Diagnosis
• 80% RA patients are RF+
• Present in sera many months before disease is
apparent
