Session 3 - Autoimmunity Flashcards
Define autoimmunity.
Immune response against the host due to loss of immunological tolerance of self antigens
What is autoimmune disease?
Disease caused by tissue damage or disturbed physiological responses due to an auto immune response
What are the clinical patterns of autoimmune disease?
Organ specific = one or multiple self antigens within one single organ or tissue
Non-organ specific = wide distributed self antigens throughout the body
Multiple systems = nervous disease, respiratory disease, Endocrine disease, joint diseases, haematological disease
Name some examples of organ specific self antigens.
Hashimoto’s thyroiditis = thyroid peroxidase and thyroglobulin
Type 1 diabetes mellitus = pancreatic islet cells
Multiple sclerosis = myelin sheath (nerve fibres)
Name some examples of non-organ specific self antigens.
Autoimmune haemolytic Anaemia = red blood cells antigen
Rheumatoid arthritis = rheumatoid factor
SLE = double stranded DNA + other nuclear proteins (histones)
What are the 2 categories of hypersensitivity reactions? What do they lead to?
Autoantibody driven = complement activation, antibody mediated Cell cytotoxicity, neutrophil activation
Auto reactive T cell driven = cytotoxic T cells, macrophages
Tissue fibrosis
What are the different types of autoantibodies?
1) primary autoantibodies = rare = pathogenic:
- Anti TSHR antibodies in Graves’ disease
- anti acetylcholine receptor antibodies in Myasthenia Gravis
- Anti anti glomerular basement membrane antibodies in goodpastures syndrome
2) Secondary antibodies:
- anti nuclear antibodies in SLE
- anti gastric parietal cell antibodies in pernicious Anaemia
- anti thyroid peroxydase antibodies in Hashimoto’s thyroiditis
Define specificity.
The % Of individuals who do not have condition that the test excludes
Define sensitivity.
The % Of individuals with a condition that the test identifies.
Give some examples of IgG transfer during pregnancy and the autoimmune diseases they cause.
Maternal auto antibody to platelets = thrombocytopenia in neonate = Cell lysis
Maternal autoantibody to TSH receptor = neonatal Graves’ disease = receptor activation
Acetylcholine receptor autoantibody = neonatal myasthenia gravis = receptor blockade
Name some mechanisms of induction of autoantibody.
1) breakdown of central tolerance
- failure to delete autoreactive T cell
2) breakdown of peripheral tolerance
- regulatory T cell defects
- impaired immunomodulation
- altered self antigens
3) activation of autoreactive B cells
- T cell independent activation of B cells
- carrier effect (complex foreign self antigens)
Name the set of criteria for the diagnosis of a disease as autoimmune.
1) presence of autoantibodies/autoreactive T cells
2) levels of autoantibodies correlate with disease severity
3) autoantibodies/autoreactive T cells found at the site of tissue damage
4) transfer of autoantibody or autoreactive T cells to a healthy host induces the autoimmune disease
5) clinical benefit provided by immunodeficiency therapy
6 family history
What triggers autoimmunity?
Genetic factors:- increased risk with an affected sibling
- increased risk with an affected identical twin
- AIRE (APECED syndrome) that affect central tolerance
- autoimmune disease associated with MHC variants
Environmental factors:
- hormones
- infectious
- Drugs
Give some examples of therapeutic strategies for autoimmune disease.
- plasma exchange = myasthenia gravis, goodpastures syndrome, Graves’ disease
- immunosuppressive Drugs = anti T cell therapies (cyclosporine), anti proliferation (azathioprine), cytotoxic Drugs (cyclophosamide), anti metabolic drugs (methotrexate)
Give some examples of monoclonal antibodies used to treat autoimmune diseases.
Ri-Tu-Xi-mab (B cells)
Be-Lim-u-mab (B cells)
Epra-Tu-zu-man (B cells)
