Hypersensitivity reaction immune-based reactions

AUergy is a much misused term. The well entrenched and widely accepted term hypersensitivity is reserved here for immune-based reactions. Some nonimmune reactions such as adverse reactions to NSAIDs and contrast media are referred to as sensitivities or intolerances. 

It is important to remember that respiratory sensitization and asthma are related, but not identical, pathologies [31]. Asthma is a specific syndrome which appears to have genetic as well as environmental causes and there are numerous potential triggers which have been identified by immunotoxicologists [32], However, asthma is not the same disease as other respiratory hypersensitivity syndromes (sometimes referred to as chemical asthma, etc.) [33, 34], Various regulatory guidance documents have sought to deal with the latter disease entities to ensure that xenobiotics are assessed appropriately for their ability to induce immune-based pulmonary hypersensitivity reactions [35-37],... 

The guinea pig maximization test (GPMT) is a preferred method for the detection of skin sensitizers. It belongs to the class of adjuvant-tests, where the substance will be applied in Freund s complete adjuvant (FCA). The test is based on the possible induction of an immune response of the skin during an induction period (at least 1 week). This pretreatment of the subject will eventually result in a hypersensitive reaction during a further exposure, the so-called challenging phase. 

Skin testing is based on the application of chemical solutions on the epidermis, with (scratch-patch test) or without (patch test) scarification of the epidermis. The occurrence of a typical type IV hypersensitivity reaction — i.e. erythema, vesiculation, and evidence of cellular infiltrate — 48-96 h after application is typical for a positive reaction. A drawback of this approach is that the metabolism of the chemical, leading to the generation of a reactive metabolite, and the presentation of the chemical to the immune system may be different according to the route of entry. 

Hypersensitivity. Hypersensitivity reactions, considered to be vaccine-related based on the timing and specificity of the reactions, were reported to the United States Vaccine Adverse Event Reporting System (VAERS) following vaccination for Lyme disease and subsequently evaluated (Burmester et al., 1995 Lathrop et al., 2002). Other reported immune system-related events to vaccines included rheumatoid arthritis, immune system disorders, detection of antinuclear antibodies, lupus syndrome, and lymphocytosis (Zhou et al., 2003). These were very rare events, with each condition comprising 0.2% or fewer of the total reports. Anaphylactic responses to vaccines were also rare and were estimated at less than one case per miUion administered vaccine doses (Bohlke et al., 2003). A number of studies evaluated anaphylactic responses to the measles-mumps-rubella (MMR), hepatitis B, diphtheria or tetanus vaccines with similar findings (Dobson et al., 1995 D Souza et al., 2000 Patja et al, 2000 Pool et al., 2002). However, some of the vaccine-induced hypersensitivity reactions are attributed to components of the formulation, such as gelatin or egg, rather than the antigen itself (Patja et al., 2001 Pool et al., 2002). 

Figure 8.1-2 Mechanism-based translational approach composed of preclinical tests that may help to assess potential risk of immune-mediated drug hypersensitivity reaction (IDHR).

Because these phenomena are also observed in other acute pulmonary reactions caused by antigen-antibody complexes, it is supposed that nitrofurantoin acts similarly, although Goldstein and Janicki (1974) had no success in demonstrating the specific antibody. In contrast, Pearsell et al. (1974) assume that pathogenesis is based on hypersensitivity of the prolonged type (cell-bound immune response). 

Allergy a hypersensitivity of the immune apparatus s pathological immune reaction induced either by antibodies (immediate hypersensitivity) or by lymphoid cells (delayed type A.). Unlike the delayed type, immediate hypersensitivity can be passively transmitted in the serum. Symptoms of immediate hy-peisensitivity begin shortly after contact and decay rapidly, but delayed type symptoms do not attain a maximum for 24-48 hours then decline slowly over days or weeks Examples of immediate type A. are anaphylaxis the Arthus reaction and serum sickness. The best known A., anaphylaxia, can occur as a local (cutaneous) reaction (e.g. a rash with blisters) or as a systemic reaction (anaphylactic shock). Asthma, hay fever and nettle rashes are also examples of local anaphylactic reactions which are induced by reagins (see Immunoglobulins IgE). Only primates can be sensitized by injection with human reagins. An example of delayed type A. is the tuberculin reaction, which is based on a cellular immune response. 

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