Chapter 28: Classification of hypersensitivity reactions

Abstract

The original Gell and Coomb's classification categorizes hypersensitivity reactions into four subtypes according to the type of immune response and the effector mechanism responsible for cell and tissue injury: type I, immediate or IgE mediated; type II, cytotoxic or IgG/IgM mediated; type III, IgG/IgM immune complex mediated; and type IV, delayed-type hypersensitivity or T-cell mediated. The classification has been improved so that type IIa is the former type II and type IIb is antibody-mediated cell stimulating (Graves Disease and the "autoimmune" type of chronic idiopathic urticaria). Type IV has four major categories: type IVa is CD4(+)Th1 lymphocyte mediated with activation of macrophages (granuloma formation and type I diabetes mellitus); type IVb is CD4(+)Th2 lymphocyte mediated with eosinophilic involvement (persistent asthma and allergic rhinitis); type IVc is cytotoxic CD8(+) T lymphocyte with involvement of perforin-granzme B in apoptosis (Stevens-Johnson syndrome and toxic epidermal necrolysis); type IVd is T-lymphocyte-driven neutrophilic inflammation (pustular psoriasis and acute generalized exanthematous pustulosis). Some diseases have multiple types of immunologic hypersensitivity.

Allergic Mechanisms in Eosinophilic Esophagitis

“…Delayed-type hypersensitivity (DTH) associated with allergic inflammatory disease is classically characterized by a Th2-predominant immune response, with elevated IL-4, IL-5, and IL-13, along with eosinophilic inflammation. 22 In clinical diagnosis, patch testing, whereby antigen is applied to the skin so as to elicit a DTH-associated response, has been shown to significantly improve predictive values over SPT alone, highlighting the likely contribution of this arm of the immune response in EoE patient responses. 23 Interestingly, the IgE and T cell-mediated arms may intersect, since IgE has been shown to enhance DTH responses in mice.…”

Immune System and Atopic Disorders

“…In the clinical practice, however, its use has been challenged since it does not include all possible allergic reactions caused by medical drugs, and sometimes both humoral and cellular responses can occur at the same time [11,12]. Other scientists have proposed the existence of additional types of hypersensitivity [13,14]. However, for the clarity and simplicity of our exposition of the fundamental concepts that inspire the classification of hypersensitivity reactions, we will start here by discussing the traditional one, to give a quick overview of the different predominant scenarios (see Table 2.1), and then we will annotate some of the improvements and subtypes.…”

“…The new improvements in the original classification from Gell and Coomb, now consider that Type IIa corresponds to the former Type II, where the inflammatory response results in cell death mediated by activation of the complement, phagocytosis, or cytolysis following the binding of antibodies to cell surface antigens on the target cell. On the other hand, the newly defined Type IIb is mechanistically distinct and refers to the inflammatory response resulting in cell death which is mediated by the direct binding of antibodies to cellular receptors [14].…”

Mechanisms of Disease of Eosinophilic Esophagitis

“…Thus the role of IgE-mediated hypersensitivity remains unclear. In contrast, delayed-type, T cell-mediated reactions are increasingly understood to participate in EoE, which appears to have an immunologic response similar to delayed-type hypersensitivity characterized by Th2 responses involving interleukin 4 (IL-4), IL-5, and IL-13 and the associated eosinophilic infiltrate (52). It is currently not fully understood how allergic sensitization occurs in EoE, but mechanisms involving loss of immunologic tolerance are being elucidated.…”