S3 L1 Autoimmunity Flashcards
Define autoimmunity?
Immune response against the host due to the loss of immunological tolerance of self antigens
Define autoimmune disease?
Disease caused by tissue damage or disturbed physiological response (change in function or damage) due to an autoimmune response
What are the different classes of autoimmunity?
- Organ specific: one or multiple self antigens within one single organ or tissue
- Non-organ specific: wide distributed self antigens throughout the body
Can occur in multiple systems throughout the body
- Nervous disease
- Respiratory disease
- Endocrine disease
- Joint disease
- Hematological disease
What are examples of the organ specific autoimmune disease and their target autoantigens?
- Hashimotos → Thyroid peroxidase and thyroglobulin
- Type 1 diabetes mellitus → Pancreatic islet cells
- Multiple sclerosis → Myelin sheath (nerve fibres)
- Good pastures syndrome → Glomerular/ alveolar basement membrane (kidney)
- Addison’s disease → Steriod-21 hydroxylase (adrenal cortex)
- Graves disease → Thyroid-stimulating hormone receptor
- Myasthenia gravis → Acetylcholine receptor (neuromuscular junction)
- Pernicious anaemia → Intrinsic factor (terminal ileum)
What are examples of non-organ specific autoimmune diseases and their target autoantigens?
- Autoimmune haemolytic anaemia → Red blood cells antigens
- Rheumatoid arthritis → Rheumatoid factor (Fc portion of the IgG)
- Systemic lupus erythematosus (SLE) → Double stranded DNA (dsDNA) + other nuclear proteins (histones)
- Sjogren’s syndrome → nuclear antigens (Ro and La)
What are the most common autoimmune diseases in the UK?
SLE and Sjogren’s syndrome
What are the clinical features of the organ specific autoimmune disease? What type of hypersensitivity reaction?
Hashimoto’s → Hypothyroidism → Type IV
Type 1 DM → Hyperglycaemia → Type IV
Multiple sclerosis → Demyelinating disease → Type IV
Goodpasture’s syndrome → Glomerulonephritis → Type II
Addison’s disease → Adrenal insufficiency → Type II-IV
Grave’s disease → Hyperthyroidism → Type II
Myasthenia Gravis → Skeletal muscle weakness → Type II
Pernicious anaemia → Vitamin B12 deficiency → Type II
What are the clinical feature of the non-organ specific autoimmune diseases?
Autoimmune haemolytic anaemia → anaemia → Type II
Rheumatoid arthritis → Inflammatory arthritis + systemic features → Type IV
SLE → Multisystem disease → Type III
Sjogren’s syndrome → Dry eyes, dry mouth and arthritis → Type IV
What do autoimmune diseases result in?
- Organ specific or non organ specific are both types of hypersensitivity reactions either driven by:
→ Autoantibodies(complement activation, antibody-mediated cell cytotoxicity or neutrophil activation) or
→ Autoreactive T cell (cytotoxic T cells and macrophages) - Results in tissue fibrosis → Don’t respond to anti-inflammatory drugs or conventional drugs because of this
What is the set of criteria for the diagnosis of disease as autoimmune?
- Presence of autoantibodies/ autoreactive T cells
- Levels of autoantibodies correlate with disease severity
- Autoantibodies/ autoreactive T cell found at the site of tissue damage
- Transfer of auto-antibody or autoreactive T cells to a healthy host induces the autoimmune disease
- Clinical benefit provided by immunomodulatory therapy
- Family history
What are the different types of autoantibodies?
Primary autoantibodies (rare) aka pathogenic → drive the disease
- Anti TSHR antibodies in Graves disease
- Anti-acetylcholine receptor antibodies in myasthenia Gravis
- Anti voltage gated Ca2+ channel antibodies in Lambert-Eaton myasthenia syndrome
- Anti-anti-glomerular basement membrane antibodies in Goodpasture’s syndrom
Secondary autoantibodies → occur much later in the disease course, they do not drive the disease
- Anti-nuclear antibodies in SLE
- Anti-gastric parietal cell antibodies in pernicious anaemia
- Anti-thyroid peroxydase antibodies in Hashimoto thyroiditis
- Anti-rheumatoid factor antibodies in Rheumatoid arthritis
How do we detect autoantibodies/autoreactive T cells at the site of tissue damage?
Biopsy →
- Infiltration of T cells in thyroid gland for Hashimoto’s thyroiditis
- Immunofluorescence in Goodpasture’s disease
- Radioimmunoassay in myaasthenia Gravis
Sample of tissue →
- Indirect immunofluorescence of healthy pancreas for Type 1 DM, adrenal tissue in Addison’s disease, rat stomach in pernicious anaemia
Serum sample →
- Agglutination (antigen mixed with antibody forms a clump) for RA,
- Radioimmunoassay and immunofluorescence for SLE
RBC → Coombs test for autoimmune haemolytic anaemia
What is indirect immunofluorscence?
- Patient serum is removed and added to healthy tissue
- Serum contains the autoantibodies which result in a disease, they bind to the receptor in the tissue
- Secondary antibodies conjugated with a fluorescent dye are added and bind to the primary antibody
- When viewed under a certain light they emit a wavelength of light that can be viewed under a microscope
How can we determine whether auto-antibodies or autoreactive T cells are able to induce autoimmune disease in health tissue?
- Third trimester in pregnancy IgG are transferred from the mother to the baby
- Includes good and bad IgG
- Mother has autoimmune disease, transferred to baby, baby develop autoimmunity
- After 6 months immunity is restored in baby as the IgG are lost
e. g. maternal autoantibody to TSH receptor → disease induced Neonatal Grave’s disease → receptor activation
What causes the breakdown of tolerance and induction of autoimmunity ?
- Breakdown of central tolerance → failure to delete autoreactive T cells
- Breakdown of peripheral tolerance → regulatory T cells (Treg) defects, impaired immunomodulation, altered self antigen
- Activation of autoreactive B cells → T cell independent activation of B cells, carrier effect (complex foreign-self antigens)
