Pathogenesis of Autoimmune Disease Flashcards
What happens in rheumatoid arthiritis?
- Chronic joint inflammation that can result in joint damage
- If untreated -> pain, discomfort and destruction of the joint
- Site of inflammation is the synovium (lining of synovial joints) - chronic sinovitis
Which antibodies are associated with rheumatoid arthritis?
Rheumatoid factor
Anti-cyclic citrullinated peptide (CCP) antibodies
What is an enthesis?
where the tendon inserts into the bone
What happens in ankylosing spondylitis?
- Chronic spinal inflammation that can result in spinal fusion and deformity
- Untreated -> pain and inflammation of the spine, bony fusion of the vertebrae
- Patients have an exaggerated thoracic kyphosis
- Site of inflammation is the enthesis (joints vertebrae together)
- ENTHESITIS -> calcium deposition and BONY FUSION
- No autoantibodies (‘seronegative’)
What are examples of seronegative spondyloarthropathies?
- Ankylosing spondylitis
- Reiters syndrome and reactive arthritis
- Arthritis associated with psoriasis (psoriatic arthritis)
- Arthritis associated with gastrointestinal inflammation (enteropathic synovitis)
What happens in systemic lupus erythematosus?
- Chronic tissue inflammation in the presence of antibodies directed against self antigens
- PATHOGENESIS IS DRIVEN BY AUTOANTIBODIES AND IMMUNE COMPLEXES (antibody + antigen)
- antibodies are referred to anti-nuclear antibodies
- Multi-site inflammation but particularly the joints, skin and kidney
- Immune complexes trigger inflammation by activating complement and binding to Fc receptors for antibody (can be inflammatory and anti-inflammatory). Because immune complexes can circulate all over the body and deposit in various places, the problems that occur in SLE are very widespread
What are examples of connective tissue diseases?
- Systemic lupus erythematosus
- Inflammatory muscle disease: polymyositis, dermatomyositis
- Systemic sclerosis
- Sjogren’s syndrome
- A mixture of the above: ‘Overlap syndromes’
What is a HLA?
human leukocyte antigen
encoded in a gene locus called the major histocompatibility complex
They encode surface proteins. There are various serotypes.
What are the types of HLA moleucules?
MHC class I : HLA - A,B.C
MHC class II : HLAA - DR molecule
Which class of MHC are SLE, rheumatoid arthritis and ankylosing spondylitis associated with?
SLE and rheumatoid arthritis - MCH Class II
ankylosing spondylitis - MCH Class II
What is the role of MCH Class I and II molecules?
present antigens to T cells
- Class I HLA molecules are present on ALL nucleated cells, and bind endogenous antigens - they are recognised by CD8+ T-cells
- Class II HLA molecules are present on APCs (dendritic cells, B cells, macrophages etc.) - generally present exogenous molecules, and recognised by CD4 T-cells
What antibodies are associated with SLE?
- Antinuclear antibodies
- Anti-double stranded DNA antibodies
What do antinuclear antibodies react to?
antigen deep in the cell, within the nucleus
What’s the next step if ANA is positive in the lab?
perform further tests to determine which type of ANA it is
- Typically these include screening for: Anti-Ro, Anti-La, Anti-centromere, Anti-Sm, Anti-RNP, Anti-ds-DNA antibodies and Anti-Scl-70
Cytoplasmic antibodies include:
- Anti-tRNA synthetase antibodies
- Anti-ribosomal P antibodies
What does a sick lupus patient commonly have?
- Low complement levels
- High serum levels of anti-ds-DNA antibodies
