Autoimmune diseases arise from immunologically mediated tissue destruction where the antigen involved is self. Several mechanisms for explaining the pathogenesis of autoimmune diseases have been proposed.
Forbidden clone theory : All clones that interact with autoantigens are destroyed during intrauterine life, but such clones can be generated by somatic mutation in later life.
Isolated antigen theory : Antigens exposed to lymphatic system during intrauterine life are recognized as self. However, some tissues (eg the lens, thyroid, CNS) are anatomically isolated or protected from lymphocytes. In adult life, when such antigens are exposed, the immune system responds to them.
Suppressor cell (TS) deficiency : Small amounts of thyroglobulin (and other self antigens) are seen in the circulation even in normal persons, but they are below the threshold level of immune stimulation. Suppressor cells also inhibit sensitization. In people with insufficient TS activity, an inappropriate immune response occurs.
Genetic effect Autoimmune disease shows familial distribution and female superiority. Many of them are related to specific HLA types. These suggest that genetic predisposition may play a role in its etiology.
Modified antigen structure Normal tissue may be altered by microorganisms and become antigenic. Drugs such as methyl-DOPA can act as haptens that bind to cellular proteins. These altered proteins can induce an immunological response. Antibodies once produced attack not only haptens but also carrier molecules.
Cross reacting antibody : Antibodies raised against foreign antigens may cross-react with tissue proteins, such as rabies vaccine encephalitis and streptococcal rheumatic fever, and the like. In any given instance, one or more of the above mechanisms may be operable.
Several important immunological disorders
1. Organ specific disease
a. Malignant anemia: Self-antigens are stomach parietal cells (diagnostic test - immunofluorescence test) and intrinsic factor (neutralization test).
b. Ulcerative colitis: autoantigen is lipopolysaccharide of colonic immunized mucosal mucosa)
c. Acute posterior streptococcal nephritis: Self antigens are streptococcal antigens (complement fixation test and immunofluorescence test).
d. Sympathetic blepharitis: Self antigen is leukocyte protein test.
e. Bullous pemphigoid: The autoantigen is the basement membrane (Immunoflourescence tests).
f. Pemphigus vulgaris; autoantigen is desmosomes (Immunoflourescence tests).
g. Thyrotoxicosis by LATS (long-acting thyroid stimulating agent): Cell surface receptor protein (bioassay).
h. Hashimoto's thyroiditis: thyroglobulin microsomes (passive haemagglutination and complement fixation test).
2. It affects two or more organ systems
a. Goodpasture's syndrome: glomerular and pulmonary basement membrane (immunofluorescence test).
b. Autoimmune hemolytic anemia: RBC membrane protein (Coombs test).
c. Immune thrombocytopenia: Platelet component (demonstration of antibodies)
d. Myasthenia gravis: skeletal muscle, heart and thymus muscle myocytes (immunofluorescence test).
e. Primary biliary cirrhosis: liver and kidney mitochondria (immunofluorescence test).
f. Rheumatic fever: Streptococcal antigen (immunofluorescence) cross-reacting with the heart and joint tissues.
3. Systemic disease or systemic disease
a. Rheumatoid arthritis: immunoglobulin, especially IgG (latex aggregation)
b. Sjogren's disease: glandular Ductus mitochondria (Immunoflourescence tests).
c. Systemic lupus erythematosus: nuclear DNA and nuclear protein (immunofluorescence test).
d. Systemic sclerosis (scleroderma): nuclear protein (immunofluorescence test).
