The Immunopathology of Hypersensitivity Reactions

Vincent A. Marinkovich, M.D.

Clinical Associate Professor, Stanford Medical School,

Overactivity of the immune system, either allergy (IgE) or hypersensitivity (non-IgE) is responsible for more illness than is generally appreciated, even by the medical profession. The least understood are the non-IgE mechanisms which involve either immune complex formation (type III of Gell and Combs) or direct killer T-cell involvement (type IV). Type III reactions may be localized with a large deposition of antigen at a focal point where immune complexes are formed and tissue damage ensues including necrosis. This is termed the Arthus reaction. A systemic dissamination of antigens will provoke a systemic inflammentory reaction which is most closely modeled by the well studied acute and chronic serum sickness reaction. Serum sickness was identified as the constellation of symptoms which followed the aadministration of antitoxins (antisera given for infectious disease before the advent of antibiotics) which were derived from non-human sources, most often horses. Chronic serum sickness was observed when otherwise heaalthy subjects were given repeat doses of antisera experimentally over relatively short periods of time. The symptoms observed in spontaneous and experimental serum sickness included fatigue, rash, cognitive changes, myositis, arthritis, headache, weight-loss, cardiovascular symptoms etc., which are often seen during heavy chronic exposure to fungal spores. The dynamic nature of circulating immune complexes, their complexity, their rapidly changing exquilibrum patterns aaand their pathogenicity must be appreciated before the clinican can properly interpret the patterns of illnes his patientsí describe. The best simple test identifying and thereby allowing the avoidance of serum sickness is a specific IgE test to a panel of high exposure antigens including fungi, food and occupational antigens.