Autoimmune Diseases

Loss of self-tolerance (tolerance is the ability to recognize self proteins as self and not as foreign)

Type I Autoimmunity

Antibodies to infectious agents cross react with self-proteins on host cells.

• Autoimmune hepatitis - anti-Hepatitis C virus antibodies cross react with hepatic antigens.
• Rheumatic fever - antibodies made against ß-streptotocci cross-reaction with heart muscle antigens or cross-reaction with antigens deposited in joints.

Type II (Cytotoxic) Autoimmunity

Antibodies bind to host cell surface antigens without cell destruction.

• Graves’ disease – thyroid stimulators bind to TSH receptors and stimulate thyroid hormone release; bypasses negative feedback loop that shuts down TSH release and results in hyperthyroidism.
• Myasthenia gravis – antibodies bind to Ach receptors and block the neuromuscular junction, muscles become progressively weaker.

Type III (Immune Complex) Autoimmunity

Antibodies against self proteins cause immune complex deposition and complement fixation, leading to inflammation and tissue destruction.

• Systemic Lupus Erethymatosus - antibodies react with self proteins including nuclear antigens, which are exposed only upon cellular damage. Damage to glomeruli is particularly common.
• Rhematoid Arthritis - anti-IgG IgM antibodies bind to the Fc portion of normal IgG antibodies and deposit in joints. Complement fixation and inflammation lead to joint destruction.

Type IV (Cell-Mediated) Autoimmunity

Activation of cytotoxic T-cells by infectious agents followed by cross-reactivity with normal host cells.

• Multiple sclerosis - destruction of myelin sheath
• Hashimoto’s thyroiditis - CTLs attack the thyroid, causing destruction of the gland
• Insulin-dependent diabetes mellitus - virally activated CTLs attack ß-cells in the pancreatic islets.