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Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality
beginning several hours after immunization and usually reaching a peak 12 to 36 hours after immunization. They are self-limited, resolving over the course of a few days. Their frequency and severity can be lessened by spacing immunizations more widely, as has been recommended for tetanus-diphtheria toxoid booster injections.
Generalized Arthus reactions of a serum sickness-like character have also been invoked following vaccine administration. Such generalized serum sickness-like reactions were common in the era when horse serum was used to treat or prevent many infectious diseases and when very large quantities of immunogenic foreign protein were infused (sometimes repeatedly). These reactions require both IgG antibody and circulating excess antigen. Considering the small quantity of protein in present-day vaccines that is injected, it is not clear that such reactions could occur as a result of immunization. In animal models, symptoms and pathology tend to localize in the kidney, skin, joints, lung, and brain (Henson, 1982). The manifestations after vaccination most commonly ascribed to serum sickness-like mechanisms are arthritis and fever.
Delayed-type hypersensitivity (type IV reaction) results from the stimulation of antigen-specific lymphocytes with the resultant replication of these cells at the site of exposure to antigen. This stimulation induces the release of lymphokines, migration of macrophages to the site, further immunologic stimulation, and resultant tissue damage. As with IgG antibody responses, this form of hypersensitivity represents the normal immunologic response to certain types of foreign antigen, and it is seen commonly after recovery from natural infections. On first exposure, the response peaks after about 3 weeks; on reexposure, the response typically peaks after 24 to 48 hours.
Delayed-type hypersensitivity has been thought to be involved in the development of neurologic complications of vaccination, particularly the development of neurologic disease after receipt of the early rabies vaccines (no longer in use) because of the large quantities of contaminating nervous system antigens in the vaccines. The possible involvement of delayed-type hypersensitivity in reactions to contemporary vaccines is discussed in the chapters on the specific vaccines and adverse events.
EFFECT OF VACCINES ON THE IMMUNE SYSTEM
The capacity of the injection of capsular polysaccharide (PRP) from Haemophilus influenzae type b to transiently decrease antibody specific to (and only to) H. influenzae type b is discussed in Chapter 9. A different question has been raised, that is, the possibility of a generalized immuno-