Classification of Hypersensitivity Reactions

Rajan TV. 2003. The Gell-Coombs classification of hypersensitivity reactions A reinterpretation. Trends Immunol. 24 376-379. 

TABLE 32.7. Gell and Coombs Classification of Hypersensitivity Reactions... 

Coombs, R.R.A. and Gell, P.G.H. (1975). Classification of allergic reactions responsible for clinical hypersensitivity and disease. In Clinical Aspects of Immunology. (Gell, P.G.H., Coombs, R.R.A. and Lachman, D.J., Eds.). Blackwell Scientific Publications, Oxford, p. 761. 

However, there are times when the immune system acts in an exaggerated manner leading to tissue damage. This is referred to as hypersensitivity. In the classic Coombs and Cell classification system, there are four types of hypersensitivity reactions. The first three (types 1-3) are mediated by antibody (e.g., IgG, IgE). The fourth type (type 4) is mediated by antigen-specific T cells and is also known broadly as delayed-type hypersensitivity (DTH). It is delayed because the reaction appears hours to days after antigen crosses into the skin. Though often thought of as... 

Autoimmunity. Autoimmune diseases are disorders of immune regulation in which several different factors (e.g. viral, genetic, hormonal, environmental) may each play a role. Autoimmune diseases may belong to any of the four Coombs and Cell classifications of hypersensitivity and include the production of autoantibodies, destructive inflammatory cell infiltrates in various organs, and deposition of immune complexes in vascular beds. Chemically induced autoimmunity may result from any of several possible mechanisms. These include the alteration or release of autoantigens, or the cross-reaction of the chemical with autoantigens, or alternatively a direct effect on the immune system via lymphocytes or macrophages (60). 

Conston AS (1974) Hypersensitivity myocarditis a fatal reaction. J Med Soc NJ 71 61 Coombs RRA, Gell GPH (1953) Classification of allergic reactions responsible for clinical hypersensitivity and disease. In Gell PG, Coombs RRA (eds) Clinical aspects of immunology. Blackwell Scientific, Oxford, pp 575-596... 

In the Gell and Coombs classification of allergic reactions, four types of hypersensitivities designated types I, n. III, and IV are distinguished. 

Table 3. Grade of severity for quantification of immediate hypersensitivity reactions (according to the classification from the French Society for Anesthesiology)... 

Hypersensitivity reactions with P-lactam antibiotics, especially penicillin, may encompass any of the type I through IV Gell-Coombs classifications. The most common reactions are maculopapular and urticarial eruptions.7 While rare (less than 0.05%), anaphylaxis to penicillins causes the greatest concern because they are responsible for the majority of drug-induced anaphylaxis deaths in patients, accounting for 75% of all ana-i phylaxis cases in the United States.5,8 The treatment of ana-I phylaxis is given in Table 51-2.9... 

The penicillins [pen i SILL in] are the most widely effective antibiotics and are among the least toxic drugs known the major adverse reaction to penicillins is hypersensitivity. The members of this family differ from one another in the R substituent attached to the 6-aminopenicillanic acid residue. The nature of this side chain affects their antimicrobial spectrum, stability to stomach acid, and susceptibility to bacterial degradative enzymes (P-lactamases). Figure 30.1 shows the main structural features of the penicillins. Figure 30.2 shows the classification of agents affecting cell wall synthesis. 

Classification of chemically induced hepatotoxicity is primarily based upon pattern of incidence and histopathological morphology. Intrinsic hepatotoxic drugs demonstrate a broad incidence, dose-response relationship and will usually give similar results in humans and experimental animals. The incidence of liver damage from idiosyncratic hepatotoxicants is limited to susceptible individuals and results from hypersensitivity reactions or unusual metabolic conversions that can occur due to polymorphisms in drug metabolism genes (see Chapters 11 and 13). 

Hypersensitivity reactions to parahens, generally of the delayed type and appearing as contact dermatitis, have been reported. However, given the widespread use of parabens as preservatives, such reactions are relatively uncommon the classification of parabens in some sources as high-rate sensitizers may be overstated. ... 

Hypersensitivity can be defined as an exaggerated response of the immune system leading to host tissue damage. However, some of the immune responses described in the hypersensitivity classification below are, in some circumstances, appropriate responses to invading antigen. For example, a component in what is an appropriate immune response to tissue transplant rejection can be defined as a type II hypersensitivity reaction. 

The use of 1 per cent as the concentration limit for classification of non-gaseous preparations (or 0.2 per cent for gaseous preparations) with respect to respiratory hypersensitivity is somewhat arbitrary, and it is feasible that some relatively potent substances present at levels below this limit may still be able to induce asthma. In these circumstances, scientific evidence that the standard concentration limit (i.e. 1 per cent) is inappropriate for protective purposes can be used to set a limit that is specific to the chemical—there is space in the Annex 1 entry for each substance for any such specific concentration limit. There may also be concern that subjects who are already sensitized would be unlikely to be protected by a 1 per cent limit from an asthmatic reaction provoked by the substance, since it is thought that provocation can occur at much lower... 

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