Autoimmunity Flashcards
Define autoimmunity
An immune response against the host due to loss of immunological tolerance to self antigens
Define autoimmune disease
Disease caused by tissue damage or disturbed physiological responses due to an auto immune response
What is the difference between organ specific and non-organ specific autoimmune disease?
Organ Specific: one or multiple self antigens within a single organ or tissue
Non-organ Specific: wide distribution of self antigens throughout the body (mostly involving type III hypersensitivity immune complex)
What do most autoimmune diseases evolve into?
Tissue fibrosis
What are the 6 criteria used to diagnose a disease as autoimmune?
- Presence of autoantibodies/autoreactive T cells
- Levels of autoantibody correlate with disease severity
- Autoantibodies/ autoreactive T cells found at site of tissue damage
- Transfer of autoantibodies to a healthy host induces autoimmune disease (done in animals)
- Clinical benefit provided by immunomodulatory therapy
- Family history (often the best indicator)
What is the difference between primary and secondary autoantibodies?
Primary: rare, known as pathogenic → antibodies drive the disease
Secondary: come later in the disease - not driving it
Give some examples of primary autoantibodies and the disease they cause
- Anti TSHR antibodies in Grave’s Disease
- Anti-ACh Receptor antibodies in Myaesthenia Gravis
- Anti-voltage-gates Ca2+ channel antibodies in Lambert-Eaton myaesthenia syndrome
- Anti Glomerular Basement Membrane antibodies in Goodpasture’s Syndrome
Give some examples of secondary autoantibodies
- Anti-nuclear antibodies in SLE
- Anti-gastric parietal cell antibodies in pernicicious anaemia
- Anti-thyroid peroxydase antibodies in Hashimoto’s disease
- Anti-Rheumatoid factor antibodies in Rheumatoid arthritis
Give examples of techniques used to identify autoantibodies/ autoreactive T cells at the site of tissue damage
- Indirect immunofluorescence
- Immunofluorescence
- Radioimmunoassay
- Infiltration of T cells
- Agglutination
- Coombs test (autoimmune haemolytic anaemia)
Which type of antibody can be transfered during pregnancy?
IgG
Usually causes a transient problem as maternal IgG lasts for only 6 weeks
What mechanisms of breakdown of tolerance induce autoimmunity?
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Breakdown of central tolerance
- Failure to delete autoreactive T cells
-
Breakdown of peripheral tolerance
- Regulatory T cells defects
- Impaired immunomodulation
- Altered self-antigens
-
Activation of autoreactive B cells
- T cell independent activation of B cells
- Carrier effect
What genetic factors suggest genes are involved in autoimmunity?
- Increased risk with an affected sibling (x8)
- Increased risk with an affected identical twin (x30)
- AIRE mutations affect central tolerance
- Autoimmune disease associated with MHC variants (HLADR3/DR4)
Which gender is more commonly affected by autoimmune disease?
Females
(80% are female, link is unclear)
What is mimickry?
Similarity of microbes/ pathogens to host tissue can induce autoimmune disease as host tissues are attacked by the immune system
Give examples of diseases caused by mimickry and the microbe involved
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Rheumatic Fever:
- Streptococcus pyogenes M protein similar to antigen in cardiac muscle
-
Guillan-Barré syndrome:
- Campylobacter jejuni glycoproteins similar to myeln associated gangliosides
-
Diabetes (type 1):
- Coxsakieviruse B4 nuclear protein similar to pancreatic islet cells
