3.1 Autoimmunity Flashcards
What are some key points about autoimmune diseases?
- Autoimmune diseases are increasing
- 80% are women
- Increased morbidity and mortality
- Manifests during adolescence and adulthood mainly
- Incurable but managable
What parts of the body are affected by autoimmune conditions?
Any organ
What is autoimmunity?
Immune response against host due to loss of immunological tolerance of self-antigens
What is autoimmune disease?
Conditions caused by tissue damage or disturbed physiological responses due to an immune response against self-antigens
What is immunological tolerance?
Host processes that prevent potentially harmful immune responses against host or self antigens
What mechanisms lead to the breakdown of immunological tolerance?
- Breakdown of central tolerance-failure to delete autoreactive T or B cells
- Breakdown of peripheral tolerance-regulatory T cell defects, impaired immunomodulation, altered self-antigens
- Activation of autoreactive B cells-T cell-independent activation of B cells, carrier effect (complex foreigen-self antigens)
What is the difference between organ specific and non-organ specific autoimmune disease?
Organ specific
- One of multiple self-antigens within one single organ or tissue
Non-organ specific
- Widely distributed self-antigens throughout the body
Outline hashimoto’s thyroiditis
Organ specific
- Thyroid peroxidase
- Thyroglobulin
TPO antibodies and thyroglobulin antibodies
Causes hypothyroidism
Type IV HSR
Graves’ disease is Type II HSR
Outline T1DM
Organ specific
- Proteins in the pancreatic islet cells
Causes hyperglycaemia
Type IV HSR
Outline multiple sclerosis
Organ specific
- Myelin sheath destruction
- Damaged oligodendrocytes
Type IV HSR
Outline goodpasture’s disease
Organ specific
- Glomerular/alveolar basement membrane
- Type IV collagen affected
Causes glomerulonephritis
Type II HSR
Outline addison’s disease
Organ specific
- Steroid-21 hydroxylase (adrenal cortex)
Causes adrenal insufficiency
Type II-IV HSR
Outline myasthenia gravis
Organ specific
- AChR destruction in the NMJ
Skeletal muscle weakness
Type II HSR
Outline pernicious anaemia
Organ specific
- Autoimmune destruction of parietal cells
- Decreased intrinsic factor, reduced B12 absorption
B12 Deficiency
Type II HSR
Outline autoimmune haemolytic anaemia
Non-organ specific
- RBC antigens
Anaemia
Type II HSR
Outline rheumatoid arthritis
Non-organ specific
- Rheumatoid factor (Fc portion of the IgG)
Inflammatory arthritis
Test via serum sample
Type III-IV HSR
Outline systemic lupus erythematosus (SLE)
Non-organ specific
- Double stranded DNA and other nuclear proteins (histones)
Multisystemic
Test via serum sample
Type III HSR
Outline sjorgen’s syndrome
Non-organ specific
- Nuclear antigens Ro and La
Dry eyes, mouth and arthritis
Type IV HSR
How can tissue damage/physiological change occur due to autoimmune disease?
Autoantibody driven:
- Complement activation
- Antibody-mediated cell cytotoxicity
- Neutrophil activation
Autoreactive T cell driven:
- Cytotoxic T cells
- Macrophages
All either type II, III or IV HSRs
What is the set of criteria for diagnosis of autoimmune disease?
- Presence of autoantibodies/autoreactive T cells
- Level of autoantibodies correlate with disease severity
- Autoantibodies/autoreactive T cells found at site of tissue damage
- Transfer of autoantibody or autoreactive T cells to healthy host induces autoimmune disease (eg vertical transmission)
- Clinical benefit from immunomodulatory therapy
- Family history
What is the difference between primary and secondary autoantibodies ?
Primary drives disease, plasmapharesis improves condition
Secondary play potential role but do not drive disease
Give 4 examples of primary autoantibodies
- Anti-TSHR-Graves’ disease
- Anti-acetylcholine receptor-Myasthenia gravis
- Anti-voltage-gated Ca2+ channel antibodies-Lambert-Eaton myasthenia syndrome
- Anti-glomerular basement membrane antibodies-Goodpasture’s syndrome
Give 4 examples of secondary autoantibodies
- Anti-nuclear antibodies-SLE
- Anti-gastric parietal cell antibodies-pernicious anaemia
- Anti-thyroid peroxydase antibodies-Hashimoto thyroiditis
- Anti-Rheumatoid Factor antibodies-Rheumatoid arthritis
What test do we use to detect antibodies?
Coomb’s Test
Auto-antibodies not always detected, cannot rule out if negative
Table for interest
