Autoimmunity
Definition: An endogenous immune response (autoantibody and/or autoreactive T cell) to an endogenous antigen
Normal Occurences
- Probably occur all of the time to help clear defective or denatured molecules
- These are rapidly cleared by the RE system
Abnormal Occurences
- when large amounts or autoantibodies or autoreactive T cells are produced which damage host tissue, an autoimmune disease is said to result
- many are organ specific while others are multi-system (classification)
- another way to classify them is by the type of autoimmune reaction causeing the disease.
Three major mechanisms recognized as causing different autoimmune disorders
1. Autoantibodies are directed against a specific self-component
- myasthenia gravis
- Grave’s disease
- lupus- skin rashes or congenital heart block
- evidenced in the fact that maternal IgG can cross the placenta and these autoantibodies produce the same reactions/interactions/diseases in the newborn
2. Autoantibodies bind with their antigens, circulate as immune complexes, and deposit in organs, causing an inflammatory response
- lupus glomerulonephritis
3. Autoreactive T cells may be directed to their target antigens and cause organ damage.
- Hasimoto’s thyroiditis
Etiology of Immune Responses
Ø mechanisms underlying unknown
Ø Genetic factors play some role because of the following observances:
1. Autoimunity runs in families
2. Greater concordance for autoimmune diseases in monozygotic twins than dizygotic twins (not 100% which leads to the idea that there are other environmental or mutational factors involved)
3. Genetic polymorphisms of MHC Class II genes are associated with increased susceptibility of all these diseases.
Possible mechanisms for a loss of tolerance
1. A lack of deletion of autoreactive T cells in the thymus during development.
2. Excessive t cell help via the loss of normal T cell suppressors
3. Excessive B cell function due to polyclonal activation of B cells by exogenous factors.
4. Cross-reactivity between exogenous and self antigens- ex. Rheumatic fever
Examples of Autoimmune Diseases
Disease: Organ Specific diseases, Autoimmune hemolytic anemia
Autoimmune Mech: Autoantibodies to RBC Antigens
Clinical Result: Lysis of RBCs and anemia
Disease: Myasthenia Gravis
Autoimmune Mech: AutoAb to ACh receptor in neuromuscular junction
Clinical Result: Blockage of NMJ trans. And muscle weakness
Disease: Graves’ disease
Autoimmune Mech: AutoAb to receptor for TSH
Clinical Result: Stimulates increased release of thyroid hormone (Hyperthyroid)
Disease: Hashimoto’s thyroiditis
Autoimmune Mech: AutoAb and Autoreactive T cells to Thyroglobulin and thyroid microsomal Ag
Clinical Result: Destruction of thyroid gland (hypothyroid)
Disease: Type I diabetes
Autoimmune Mech: AutoAb and Autoreactive Tcells to pancreatic islet cells
Clinical Result: Destruction of islet cells and failure of insulin prod.
Non-Organ-Specific or Systemic diseases
Disease: Systemic Lupus erythematosus
Autoimmune Mech: AutoAb to nuclear Ag. inc. anti-DNA, orm circulating Immune complexes (Kidneys, skin, et al) depositing in skin, kidneys, et al.
Clinical Result: Damage to many organs
Disease: Rheumatoid arthritis
Autoimmune Mech: AutoAb to IgG form immune complexes in synovium of joints and elsewhere. Also, infiltrating T cells in synovium and bone
Clinical Result: Inflammation and ultimate destruction of cartilage
AutoAb can be detected in the blood of patients with these autoimmune diseases
Ø Antinuclear antibodies- test for SLE
Ø IgM Ab to IgG- rheumatoid arthritis (though not as specific)
Tags: autoantibodies, Autoimmunity, autoreactive T cells, B cell, congenital heart block, endogenous immune response, Genetic polymorphisms, Grave's disease, Hasimoto's thyroiditis, lupus glomerulonephritis, myasthenia gravis, Rheumatoid arthritis, T cell suppressors, thyroglobulin, thyroid microsomal
