sensitivity as proposed by Coombs and Gell (1968). However, the response to any one antigen may involve a combination of types of hypersensitivity, depending on the antigen dose, site of exposure, and duration of antigen stimulation. Type I hypersensitivity is a response to the antigen that occurs within minutes; symptoms range from a mild rash or urticaria to airway obstruction or acute life-threatening anaphylactic shock. In Type II reactions, antibodies combine with a tissue antigen, resulting in complement system activation and damage to the tissue by the inflammatory process. Drug-induced hemolytic anemia is an example of a Type II hypersensitivity reaction. Type III hypersensitivity involves the interaction of circulating antibody and antigen to form immune complexes that deposit on the walls of blood vessels. The resultant fixation of complement and neutrophil recruitment leads to tissue destruction. The pathology of Type III hypersensitivity tends to be seen in the lung, kidney, joints, and brain in animal studies. A localized reaction in the skin can lead to pain, swelling, induration, and edema. Type IV hypersensitivity or delayed-type hypersensitivity is dependent on the stimulation of antigen-specific lymphocytes and recruitment of macrophages by cytokines. The resultant inflammation leads to tissue destruction. Contact dermatitis to poison ivy is an example of a Type IV hypersensitivity reaction. Animal studies have limitations in detecting adverse effects due to Types II through IV hypersensitivity because the time course of such responses may involve months or years to become clinically apparent in an animal, which is beyond the time frame monitored in most animal studies.

Genetic inheritance strongly influences the immune response, both to immunization and to actual infection (Box 7.1), in animals and humans, which explains why immunologically mediated adverse reactions to vaccination are so variable from one animal, or person, to the next.


Work on a vaccine to provide protection against the zoonotic disease anthrax3 began with the work of Pasteur and Greenfield who developed heat-attenuated anthrax vaccines in the 1880s (Turnbull, 1991). In the 1930s, Sterne developed a live attenuated spore vaccine, and versions of this vaccine continue to be used effectively to immunize livestock. The primary use of the anthrax vaccine in humans was initially to protect persons working with animal hair or hides, including goat hair mill workers, tannery workers, and veterinarians.


Anthrax occurs most commonly in herbivores who ingest anthrax spores from the soil. Naturally occurring cases of human anthrax are the result of contact with anthrax-infected animals or contaminated animal products. There are three clinical forms of human anthrax infection: inhalation, cutaneous, and gastrointestinal. Inhalation anthrax naturally occurs only rarely, but the mortality rate approaches 100 percent (Fauci et al., 1998). Since 1950, the incidence of the disease in animals and man has dropped markedly due in large part to the availability of the vaccine, the use of antibiotics, and the implementation of strict quarantine laws in many countries (Whitford, 1987).

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