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
How are autoantidobies detected at site of tissue damage?
- Indirect immunofluoresence
- Immunofluoresence
- Radioimmunoassay
- Coomb’s test
- Agglutination
Take biopsy then test^
What histological feature is present on hashimoto’s thyroiditis?
Lymphocytic inflitration
Complete the table
What does it mean that myasthenia gravis is transient in neonates?
Mother’s autoantibodies are replaced by own body’s antibodies when the immune system matures
How do you treat neonatal myasthenia gravis?
Neostigmine
ACh Esterase inhibitor
What triggers autoimmunity?
Genetic factors
- Increased risk with affected sibling or identical twin
- AIRE mutations that affect central tolerance (gene codes for T cells to not attack self antigens)
- MHC variants (HLADR3/4)
Environmental factors
- Hormones
- Infections
- Drugs
What is the significance of hormonal factor involvement in autoimmune disease?
Females affected much more
In pregnancy hormones released by placenta can improve some autoimmune conditions
What is another reason that females are affected by autoimmune conditions more than men?
Females are XX
1 X should be inactive, but in some cases 25% of genes are active on the second X chromosome
Can cause problems with immune regulation
Complete the table
