Pathogenesis of Autoimmune Disease Flashcards
(44 cards)
what is rheumatoid arthritis (RA)?
synovitis
chronic joint inflammation and therefore joint damage, pain and stiffness
SYMMETRICAL
what are the associated anti-antibodies in RA?
o Rheumatoid factor.
o Anti-cyclic citrullinated peptide (CCP) antibodies
what is ankylosing spondylitis?
enthesis
chronic spinal inflammation causing spinal fusion and deformity.
what are the associated auto-antibodies in anky.spond?
none
seronegative disease
what are some examples of seronegative spondyloarthropathies?
spondyloarthropathies are seronegative by definition (shown by the absence of rheumatoid factor)
o Ankylosing spondylitis. o Reiter’s syndrome (reactive arthritis) o Psoriatic arthritis – arthritis associated with psoriasis. o Enteropathic synovitis – arthritis associated with GI inflammation.
what is systemic lupus erythematosus (SLE)?
immune complexes mediated
Chronic tissue inflammation from antibodies directed against self-antigens.
usually involves skin, joints, kidneys and other organs
which site does SLE commonly inflame?
joints
skin
kidneys
what are the associated auto-antibodies in SLE?
o Anti-nuclear antibodies.
o Anti-double-stranded DNA antibodies.
what are some examples of connective tissue disorders?
- SLE
- Inflammatory muscle disease (polymyositis, dermatomyositis)
- Systemic sclerosis
- Sjogren’s syndrome
- “Overlap” syndromes (mixtures)
what HLA is associated with RA?
HLA-DR4
what HLA is associated with SLE?
HLA-DR3
what HLA is associated with anky.spond?
HLA-B27
what do HLA encode for?
MHC class I and II
which chromosome do HLA class I and II come from?
Chr 6
which chromosome does the beta 2 microglobulin of HLA class I come from?
Chr 15
what do HLA molecules do?
present to T cells
o Class 1 –> CD8+ T-cells (cell killing).
o Class 2 –>CD4+ T-cells (helper T-cells).
T cells are MHC restricted i.e. only method of seeing an antigen
describe the structure of the peptide binding site for HLA molecule to T cells?
o Walls - alpha-helical structures.
o Floor - beta-pleated sheet.
what are peptide antigens bind to HLA molecules to trigger disease?
Arthritogenic antigens (these can be exogenous or self) o E.G. Antigen-HLA-B27 --> (MHC class 1)--> triggers CD8+ T-cell response in Ankylosing Spondylitis.
o E.G. Antigen-HLA-DR4–> (MHC class 2)–> triggers CD4+ T-cell response in RA (therefore involves antibodies)
what class HLA is associated with RA?
MCH Class 2
HLA DR4
what class HLA is associated with SLE?
MHC Class 2
HLA DR3
what class HLA is associated with anky.spond?
Class 1
however studies in rats show that anky.spond can be triggered independent of T cells (CD8+) when they express HLA-B27 and T cells were removed
what does the updated theory on anky.spond describe is the genetic abnormality?
abnormalities in both HLA-B27 AND IL-23 pathway
HLA-B27 has a propensity to miss-fold to cause cellular stress and triggers IL-23 pathway to trigger IL-17 production
how is IL-17 product triggered by the IL-23 pathway?
• Adaptive immune cells
– CD4+ Th17 Cells.
• Innate immune cells
– CD4-, CD8- (‘double negative’) T-cells.
The “double negative” T-cells have been detected in enthesis and could be the reason for enthesopathy in AS.
what are anti-nuclear ABs directed against in SLE?
the nucleus
there are auto antigens in the nucleus but <100 react to ANAs
of those, only a few react in SLE
