The Immunopathology of Hypersensitivity Reactions

September 9, 2010

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 patients' 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.

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