7: Pathogenesis of Autoimmune Disease Flashcards
Which MHC is associated with Rheumatoid arthritis?
HLA- DR4
Which MHC molecule is associated with suspectibility to SLE?
HLA-DR3
Wich MHC molecular is associated with the development of Ankylosing Spondylitis?
HLA-B27
What is Ankylosing spondolytis?
It is a type of seronegative spondyloarthropathies characterised by:
- Chronic spinal inflammation that can result in spinal fusion and deformity
- loss of curvature in lumbar spine du
- Site of inflammation is the enthesis
- site where ligaments and tendons insert the bone
- No autoantibodies (‘seronegative’)
Explain the function of MHC-Type I molecules in antigen presentation
- Present on all nucleated cells
- Present to CD8- T cells
- Portrait of normal self or abnormal self (e.g. viral proteins on surface, tumor antigens
- If abnormal: apoptosis
Explain the function of MHC-Type II molecules in antigen presentation
- only present on “professional” antigen presenting cells
- Present to CD-4 T cells
- Present exogenous antigens
- Cause antibody response if presented
Explain the role of HLA molecules in the pathogenesis of rheumatologic dieases
Possible
- an antigen binds to HLA (can be endogenous or exogenous) and triggers disease
- E.g. in ankylising spondolytis: antignes bind to HLA-B27 and cause disease etc.
What are the key antibodies in SLE?
How can they be used diagnostically and in monitoring the disease?
- Anti-Nuclear antibodies (ANA)
- always present, not very specific but can probably be seen in all patients with SLE
- Specifically: anti-dsDNA (antibodies against double stranded DNA)
- Highly specific,
- Serum levels correlate with disease activity –> can be used in monitoring of disease (e.g. high anti-dsDNA, low complement –> treatment)
What are the Key antibodies associated with Rheumatoid arthritis?
- Rheumatoid Factor
- Anti-cyclic citrullinated peptide antibody (ACPA)
- also termed antibodies to citrullinated peptide antigens (ACPA)
What kind is the Rheumatoid Factor?
It is an IgM antibody against IgG (Fc poartion of IgG),
seen in Rheumatoid arthritis
What are the key antibodies seenin
- reactive arthritis
- osteoarthritis
- gout
- Ankylosing Spondylitis
NONE
- are all serumnegative to antibodies
Explain the pathogenesis of Systemic Lupus Erythematosus
In apoptosis: translocation of nuclear antigens to the cell surface
In Lupus
- Impaired clearance of apopototic cells leads to enhanced presentation of nuclear antigens to immune cells
- B-cell auto-immunity
- Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
What are the major cytokines involved in the formation of Rheumatoid arthritis?
Mainly : TNF-alpha
- but also: IL-1, 6, 13,
What is the scinetific basis for the use of TNF-alpha inhibitors in the treatment of Rheumatoid arthritis?
Studies in rheumatoid synovial cultures showed
- TNF-a was dominant cytokine
- i.e. inhibition of TNF-a resulted in blockage of production of interleukin-1, interleukin-6, the chemokine interleukin-8 and GM-CSF
Explain the role of RANKL in Rhematoid arthritis
RANKL (receptor activator of nuclear factor kB ligand) is produces by fibroblast and T cells in inflammed joint and causes
- osteoclast activation (via binding to RANK)
