Role in Immune Pathology
Contact with an antigen does not always result solely in a protective response—sometimes mechanisms that damage the body's own tissues are triggered. Such conditions are called hypersensitivity reactions.
They are divided into 4 types depending on the immunological mechanism. While Type II involves cytotoxic antibodies, Type III involves immune complexes, and Type IV involves cell-mediated lymphocyte responses, Type I is characterized by the rapid release of spasmogenic and vasoactive substances.
Pathogenesis: From Contact to Degranulation
The development of anaphylactic reactions is based on the interaction of an allergen with IgE antibodies. The process occurs in several stages:
- Primary contact: the antigen enters the body, activating B cells, which begin to synthesize IgE.
- Sensitization: IgE molecules bind firmly via their Fc region to receptors on the surface of mast cells and basophils.
- Re-exposure: the allergen cross-links IgE molecules on the surface of the previously sensitized mast cell.
- Activation and degranulation: the cell releases preformed primary mediators and begins de novo synthesis of secondary mediators (from arachidonic acid metabolites).
Interestingly, mast cells can also be activated without antigen involvement. Triggers can include complement anaphylatoxins (C3a and C5a), macrophage cytokines (IL-8), physical factors (heat, cold, sunlight), and even certain drugs (morphine, codeine).
Two Phases of the Allergic Response
The immediate-type reaction unfolds over time and has two distinct stages, differing in their mediators and clinical effects.
Early Phase Begins 5–30 minutes after exposure to the allergen. The main sources of mediators here are basophils and mast cells, which release histamine and leukotrienes. This leads to vasodilation, increased vascular permeability, mucosal edema, hypersecretion of mucus, and smooth muscle spasm.
Late Phase Starts 2–8 hours later, even without re-exposure to the antigen, and can last for several days. Driven by platelet-activating factor (PAF) and tumor necrosis factor-alpha (TNF-α), inflammatory cells are recruited to the tissue: monocytes, neutrophils, basophils, and, most importantly, eosinophils. The outcome of this phase is epithelial cell damage.
Role of Eosinophils
Eosinophils are key players in the late phase. They share a wide spectrum of mediators with mast cells, but additionally secrete specific toxic proteins:
- MBP (Major Basic Protein);
- ECP (Eosinophil Cationic Protein).
Under normal conditions, these proteins are vital for destroying parasites and microorganisms. However, in pathology (such as bronchial asthma), their aggressive action is directed against the body's own tissues, causing destruction of the airway epithelium.
Clinical Forms: Systemic and Local
The manifestations of Type I hypersensitivity depend on the route of antigen entry and the degree of sensitization.
Systemic Anaphylaxis Most commonly occurs following intravenous administration of an allergen (heterologous proteins, polysaccharides, penicillin). Anaphylactic shock develops, the severity of which directly correlates with the level of prior sensitization. Furthermore, the shock dose of the antigen can be vanishingly small.
Local Anaphylaxis (Atopic Allergy) Found in about 10% of the population and shows a strong familial predisposition. It occurs in response to exogenous allergens: house dust, pollen, animal dander, food. Manifestations depend on the site of contact:
- Skin: urticaria, angioedema;
- Mucous membranes: allergic rhinitis (hay fever), conjunctivitis;
- Respiratory tract: bronchial asthma;
- Gastrointestinal tract: food allergy (allergic gastroenteritis).