Stages of Allergic Reaction Development
The pathological response process can be divided into two key phases.
1. Sensitization Phase (Primary Antigen Exposure) An antigen-presenting cell (APC) engulfs the allergen and presents it to type 2 helper T cells (Th2). With the participation of cytokines (IL-4 and IL-13), B lymphocytes are activated, transforming into plasma cells that actively synthesize allergen-specific IgE. These antibodies attach via their Fc region to high-affinity receptors (FcεRI) on the surface of mast cells and basophils. The body becomes "primed," but no symptoms are present yet.
2. Pathochemical and Pathophysiological Phases (Re-exposure) Upon re-exposure, the allergen binds adjacent IgE molecules on the membrane of sensitized cells (cross-linking). This triggers a massive influx of calcium ions into the cell. Degranulation is initiated: preformed substances (such as histamine) are instantly released from granules, and synthesis of new lipid mediators (leukotrienes) and cytokines begins. Classical pharmacological effects ensue, affecting the vasculature, nerve endings, and respiratory tracts.
Key Mediators and Maintenance of Inflammation
Effector cells release a broad spectrum of biologically active substances that determine the severity of the condition:
- Vasoactive amines and proteoglycans: histamine and heparin.
- Lipid mediators: prostaglandins, leukotrienes, and platelet-activating factor (PAF).
- Enzymes: tryptase, chymase.
- Cytokines: IL-3, IL-4, IL-5, TNF-$\alpha$, and others.
Key concept: in addition to the classical IgE pathway, basophils possess Fc receptors for IgG. When immune complexes bind to these receptors, basophils secrete platelet-activating factor. Its ability to increase vascular permeability is 10,000 times greater than that of histamine. Activated platelets, in turn, release serotonin, which helps maintain chronic allergic inflammation.
Late-Phase Reaction and the Role of Eosinophils
Over time, additional cells (macrophages, neutrophils) are recruited to the site of inflammation, but eosinophils play a special role. Mast cells release specific eosinophil chemotactic factors (ECF), forcing eosinophils to migrate into the tissues.
At the site, eosinophils begin to secrete aggressive substances: cationic proteins, enzymes, and leukotrienes. One of the most important is major basic protein, which causes direct epithelial damage, exacerbating tissue destruction during allergic reactions.
Clinical Presentations and Diagnostic Principles
The inherited predisposition to immediate-type hypersensitivity (genetic overproduction of IgE, increased barrier permeability) is termed atopy.
Manifestations of Type I reactions are divided into:
- Systemic: Anaphylactic shock. It develops lightning-fast, is accompanied by a sharp drop in blood pressure (collapse) and bronchospasm, and carries a high risk of mortality. Common triggers include parenteral drugs and insect venom.
- Local: Allergic urticaria, angioedema, allergic rhinitis, pollinosis (hay fever), atopic asthma, and food allergy.
Diagnosis includes measuring total and specific serum IgE, as well as cell activation markers (histamine and tryptase levels). Smears (e.g., nasal) and blood tests reveal eosinophilia. In vivo provocation tests (skin tests, nasal tests) are used for confirmation.
Allergen-specific immunotherapy (ASIT)—the administration of gradually increasing doses of an allergen to achieve desensitization—is used as etiopathogenetic treatment.