General characteristics of type 1 hypersensitivity
Type 1 hypersensitivity (anaphylactic type) is a form of allergic reaction based on the production of immunoglobulin E (IgE) in response to antigens (allergens) that are harmless to most people. Typical allergens include plant pollen, household chemicals, food components, animal dander, and medications.
Pathogenesis traditionally comprises three consecutive phases: immunological (antigen recognition and IgE production), pathochemical (mast cell degranulation and mediator release), and pathophysiological (clinical manifestations caused by the action of mediators on tissues).
Immunological phase: initial contact and sensitization
Upon the first entry of an allergen into the body, it is captured by an antigen-presenting cell (APC)—most commonly a dendritic cell, less often a macrophage or B lymphocyte. The APC migrates to regional lymphoid organs, where it presents allergen fragments in the context of MHC class II to a naive T helper cell.
Activation of a naive T cell requires three signals:
- interaction between the TCR and the MHC II–peptide complex;
- costimulation via CD28 and related molecules;
- cytokine microenvironment—IL-33 and IL-25, which direct differentiation.
Under the influence of these signals, the naive T cell differentiates into a type 2 T helper cell (Th2), which drives the adaptive component of type 2 inflammation—reactions to allergens and helminths.
Th2 produces key cytokines. IL-4 switches the isotype of antibody synthesis in B lymphocytes from IgM to IgE. IL-5 activates eosinophils. The synthesized IgEs bind via their Fc fragment to high-affinity FcεRI receptors (epsilon receptors) on the surface of mast cells and basophils. At this stage, there are no clinical manifestations — the body is in a state of sensitization, i.e., readiness to react upon re-exposure to the same allergen.
Pathochemical phase: repeated contact and degranulation
Upon re-exposure to the allergen, it directly binds to IgE molecules already fixed on mast cells. Triggering the reaction requires cross-linking of at least two adjacent IgE molecules by a single antigen. This causes FcεRI aggregation and an intracellular signal leading to mast cell degranulation—the release of secretory vesicle contents into the extracellular space.
Released mediators are divided into preformed (stored in granules) and newly synthesized:
- histamine—the main preformed mediator;
- proteases (tryptase, chymase);
- eicosanoids—leukotrienes and prostaglandins synthesized from arachidonic acid;
- cytokines: IL-4, IL-5, IL-13, TNF-α.
Pathophysiological phase: effects of mediators
Histamine, acting on H1 receptors, causes bronchial smooth muscle spasm (bronchospasm, breathing difficulty), dilation of microvascular blood vessels, and increased vascular permeability. Plasma leakage into tissues manifests as edema and swelling.
Leukotrienes (especially LTC4, LTD4) sustain prolonged bronchospasm and increase vascular permeability. Prostaglandins are involved in the regulation of temperature and vascular tone. Together, the mediators reproduce the classic signs of inflammation: redness, edema, fever, pain, impaired function.
Cytokines maintain and enhance the reaction: IL-4 stimulates further IgE synthesis by B lymphocytes, IL-5 recruits and activates eosinophils, IL-13 supports the Th2 response, and TNF-α enhances inflammatory effects.
Clinical and laboratory manifestations
Clinical forms of type 1 hypersensitivity are diverse: allergic rhinitis, conjunctivitis, bronchial asthma, urticaria, angioedema, food and drug allergies, and systemic anaphylaxis. The onset speed ranges from seconds to tens of minutes after re-exposure.
A complete blood count in such patients frequently reveals eosinophilia, and less often an elevated basophil count. This is explained by the activating effect of Th2 and mast cell mediators (primarily IL-5) on the eosinophilic lineage. Elevated total and specific serum IgE levels also serve as laboratory confirmation of the reaction.
Key points
- Type 1 hypersensitivity is an IgE-mediated anaphylactic reaction to an allergen.
- Primary contact leads to sensitization: Th2 differentiation and IgE fixation on mast cell FcεRI.
- Key induction cytokines: IL-33 and IL-25 for Th2; IL-4 for B cell switching to IgE.
- Re-exposure causes IgE cross-linking and mast cell degranulation.
- Main mediators are histamine, leukotrienes, prostaglandins, proteases, and cytokines (IL-4, IL-5, IL-13, TNF-α).
- Histamine via H1 receptors causes bronchospasm, vasodilation, and increased vascular permeability.
- The reaction develops through three phases: immunological, pathochemical, and pathophysiological.
- Laboratory markers are eosinophilia and elevated blood IgE.