Pathogenesis of Autoimmune Disease Flashcards
(29 cards)
What is rheumatoid arthritis?
Joint inflammation that can result in joint damage
What is the site of inflammation in rheumatoid arthritis?
Synovium (so sometimes it is called synovitis)
What are the antibodies associated with rheumatoid arthritis?
- Rheumatoid factor (which is an autoantibody)
- Anti-cyclic citrullinated peptide (CCP) antibodies
What is ankylosing spondylitis?
Chronic spinal inflammation that can result in spinal fusion and deformity
What is the site of inflammation in ankylosing spondylitis? Are antibodies responsible?
Enthesis (so sometimes called enthesitis)
No, it is seronegative.
Name 4 seronegative spondylopathies.
- Ankylosing spondylitis
- Reiters syndrome and reactive arthritis
- Arthritis associated with psoriasis (psoriatic arthritis)
- Arthritis associated with GI inflammation (enteropathic synovitis)
Describe the spinal deformity in ankylosing spondylitis.
increased thoracic kyphosis and the loss of normal lumbar lordosis.
What is systemic luous erythematosus?
SLE = chronic tissue inflammation in the presence of antibodies directed against self antigens.
What is the site of inflammation in SLE?
Multi-site inflammation but particularly at the joints, skin and kidney.
What antibodies is SLE associated with?
SLE is associated with autoantibodies:
- Antinuclear antibodies
- Anti-double stranded DNA antibodies.
What group of diseases does SLE belong to? Name some other diseases in this category.
CONNECTIVE TISSUE DISEASES:
- Systemic lupus erythematosus
- Inflammatory muscle disease: polymyositis, dermatomyositis.
- Systemic sclerosis
- Sjogren’s syndrome
- Mixture of the above = “overlap syndromes”
What is SLE associated with in relation to antibodies?
Immune complexes.
What is the MHC? What parts of the MHC locus are these conditions associated with:
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Ankylosing spondylitis
- HLA-DR4
- HLA-DR3
- HLA-B27
MHCis the major histocomaptibility complex,
What do class I and II MHC regions encode? Which rheutamoid conditions are class I and which are class II.
Cell surface proteins.
- Class I ( HLA-A,B and C) e.g. Ankylosing spondylitis HLA-B27
- Class II (HLA-D) e.g. Rheumatoid arthritis and systemic lupus erythematosus.
What is the function of class I and II MHC molecules?
To present antigen to T cells
Describe what is meant by “MHC restriction”
- Peptide binding site is made up of walls and a floor (alpha-helical and beta pleated sheet structures respectively)
- T cells only see antigen bound to MHC = “MHC restriction”
T cell recognition of antigens is by large MHC restrictive.
Where are class I and class II MHC expressed?
Class I (HLA-A,B,C) - All nucleated cells
Class II (HLA-DR, DQ, DP) - Antigen presenting cells e.g. B cells, monocytes, macrophaes, dendritic cells.
Give examples of antigens which class I and class II MHC is responsible for presenting.
Class I - Responsible for presenting endogenous (intracellular antigens) e.g.
- viral peptides
- tumour antigens
- self-pepides
Class II- Responsible for presenting exogenous (extracellular) antigens e.g.
- bacterial peptides
- self-peptides
Which T cells are class I and II MHC molecules recognised by?
Class I CD8 +ve T cells (cytotoxic T cells)
Class II by CD4 +ve T cells (helper T cells)
What is the T cell response to presention of class I or class II antigens?
Class I - cytotoxic T cells kill the cell.
Class II - helper T cells produce an antibody response.
Describe and give examples of how HLA molecules can trigger disease.
HLA-associated disease could be due to a peptide antigen (exogenous or self) binding to HLA molecule and triggering disease (“arthritogenic disease”)
- e.g. antigen and HLA-B27 when bound together can be recognised by a CD8+ T cell and produce a response resulting in Ankylosing Spondylitis.
- e.g. antigen and HLA-Dr4 triiggers CD4+ T cell response in Rheumatoid Arthritis.
What is the name of an antigen which binds to HLA and causes disease?
Arthitogenic peptide.
What is the current theory behind the pathogenesis of ankylosing spondylitis?
No arthritogenic peptide found; though to be associated with abnormalities in both HLA-B27 and IL-23 pathway:
- HLA-B27 has propensity to misfold -> cellular stress -> triggers IL-23 release and IL-17 production. This occurs through the following T cells:
- Adaptive immune cells i.e. CD4 +ve Th17 cells
- Innate immune cells e.g. CD4 –ve, CD8 –ve (‘double-negative’) T cells
Where can “double negative” T cells be found in ankylosing sopndylitis?
Entheses which may expain why enthesopathy occurs in ankylosing spondylitis.
