Modern understanding of immune reactions and EAACI 2023 classification

In 1968, Coombs and Gell proposed a classification of allergic disorders based on then available knowledge in immunology. Four types of reactions were identified: type I , immediate (IgE-mediated); type II, cytotoxic (mediated by antibodies and Fc-receptors of cells); type III, mediated by immune complexes, and type IV, the delayed type (T-cell-mediated). This classification proved to cover pathogenesis of allergic disorders, but also the mechanisms  of autoimmune, infectious and parasitic diseases. Rapid development of immunology at the edge of XX and XXI centuries has revealed many new patterns that required updating the classification. In 2023, the European Association of Allergists and Clinical Immunologists (EAACI) proposed its own classification. It included the first 3 types from the Coombs and Gell classification. Meanwhile, the type IV cell-mediated reactions were divided into 3 subtypes: type IVa - T1 (type Th1), IVb - T2 (type Th2), IVc - T3 (type Th17). In addition, 3 more types were added: type V, with alteration of epithelial barriers; type VI, metabolically induced immune dysregulation, and type VII, with direct inflammatory response to chemicals. Unfortunately, the EAACI2023 classification does not provide a complete pattern. It does not follow a single classification principle, relying on pathogenetic, etiological, or structural aspects. But the main drawback of this classification is that the authors continue to consider allergic diseases as a separate area, while there is nothing special about them. In fact, there is no specific mechanism seen in allergic diseases that could be, at least, somehow differ from the general immunological reactions. Moreover, all these mechanisms were formed in the course of evolution as protective mechanisms, and not as pathological ones. This article concerns modern concepts of immune response, specifying 6 types of immune reactions and 5 levels of their implementation. In addition, 5 types of effector mechanisms of immune reactions are considered, forming a complex multi-level network of immune protection. The need for knowledge of immunology by clinicians of any specialty for adequate usage of immunodiagnostics and immunotherapy with bioengineered drugs is highlighted.

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