Session 3 Flashcards
Define autoimmunity
Immune response against the host due to the loss of immunological tolerance (state of unresponsiveness to self antigen) of self- antigen(s)
Define autoimmune disease
Disease caused by tissue damage or disturbed physiological responses due to an auto-immune response
Clinical patterns of autoimmune disease
2 types:
Organ specific: One or multiple self antigens within one single organ or tissue. Easier to treat as self antigen is only present in that tissue.
Non-organ specific: Wide distributed self antigens throughout the body so harder to treat.
Thres not a single organ system that cannot be affected by an autoimmune disease e.g nervous system, respiratory disease, endocrine disease, joint diseases, haemotological disease.
Some diseases can overlap e.g lupus.
Common autoimmune diseases and their target autoantigens
Organ specific
Hashimoto’s thyroiditis - Thyroid peroxidase and thyroglobulin
Type 1 diabetes mellitus* - Pancreatic islet cells
Multiple sclerosis - Myelin sheath (nerve fibers)
Goodpasture’s disease - Glomerular/alveolar basement membrane (kidney)
Addison’s disease - Steroid-21 hydroxylase (adrenal cortex)
Graves’ disease - Thyroid-stimulating hormone receptor
Myasthenia gravis - Acetylcholine receptor (neuromuscular junction)
Pernicious anaemia* - Intrinsic factor (terminal ileum)
Non-organ specific
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)
*multiple autoantigens may also be prsent in tissues.
Common autoimmune diseases,their clinical outcome and type of hypersensitivity
Set of criteria for the diagnosis of a disease as autoimmune
- Presence of autoantibodies/autoreactive T cells
- Levels of autoantibodies correlate with disease severity
- Autoantibodies/autoreactive T cells found at the site of tissue damage
- Transfer of autoantibody or autoreactive T cells to a healthy host induces the autoimmune disease
- Clinical benefit provided by immunomodulatory therapy
- Family history
Types of autoantibodies
Primary autoantibodies (rare) : (known as pathogenic)
- 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-Glomerular basement membrane antibodies in Goodpasture’s syndrome
Secondary autoantibodies
- 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
Detection of serum autoantibodies and autoimmune disease
This shows not all patients will have autoantibody against the defined self antigen.
Define specificity
Specificity = The % of individuals who do not have condition that the test excludes
Define sensitivity?
Sensitivity = The % of individuals with a condition that the test identifies
Detection of autoantibodies/autoreactive T cells at the site of tissue damage?
IgG transfer during pregnancy and autoimmune diseases
IgG can cross the placenta and cause disease in the neonate. Disease will only last 6 months though as baby forms its own antibodies after this point. IgM doesnt pass the placenta.
What triggers autoimmunity?
Genetic factors
o Increased risk with an affected sibling (8X)
o Increased risk with an affected identical twin (30X)
o AIRE mutations (APECED syndrome) that affect central tolerance
o Autoimmune disease associated with MHC variants (HLADR3/DR4)
Environmental factors
o Hormones
o Infections
o Drugs
Hormonal factors that influence prevalence of auto immune disease
Autoimmune disease more common in females. Nearly all occur during child bearing age except type 1 diabetes.
Infectious factors that affect prevalence of autoimmune disease
Similar to antigens in the body so body can attack both causing autoimmune disease.
Therapeutic drugs that can cause autoimmune disease
These drugs can cause side effects that mimic different autoimmune diseases. When they stop treatment, symptoms stop too.
Current and future therapeutic strategies for autoimmune diseases
Plasma exchange for primary antibody disease and immunosuppressive drugs for autoreactive T cell mediated disease. Monclonal antibodies being developed currently to target specific proteins so will heavily reduce side effects. If drug name ends in mab it means its a monoclonal antibody. Rituximab, belimumab and epratuzumab are against b cells and golimumab against TNF.
Which therapy for autoimmune disease?
Examination for ARDs
Muscle weekness - oppose muscle movements or ask them to get out of a chair without using their arms.
Investigations for ARDs
C-reactive protein - Will nearly always be normal regardless of how ill they are.
Dont need to know bloods.
