Allergy and Hypersensitivity

Allergy is an inappropriate immune response mounted by genetically predisposed individuals against non-pathogenic environmental antigens called allergens. It is primarily classified as a Type I hypersensitivity reaction, involving IgE and mast cells, though late-phase reactions also involve Type IV (T-cell-mediated) mechanisms. Three components are essential: the allergen (e.g., pollen, house dust mite, food proteins), the serum factor (IgE), and the tissue factor (mast cells).

Sensitisation occurs on first allergen exposure: antigen-presenting cells present allergen peptides to naive CD4 T cells, which differentiate into Th2 cells under the influence of cytokines such as IL-4 and IL-13. Th2 cells promote B-cell class switching to IgE production. IgE binds to high-affinity Fc receptors on mast cells and basophils. On subsequent allergen exposure, allergen cross-links IgE on mast cells, triggering degranulation: rapid release of preformed mediators (histamine, proteases) causes immediate symptoms (vasodilation, smooth muscle contraction, mucus secretion), while newly synthesised lipid mediators (leukotrienes, prostaglandins) perpetuate the response.

In atopic individuals, genetic factors promote Th2 skewing of immune responses, increasing susceptibility to multiple allergen sensitivities (atopy). Common atopic conditions include allergic rhinitis, asthma, atopic dermatitis, and food allergy. Anaphylaxis is a systemic, life-threatening Type I reaction involving cardiovascular collapse and airway compromise; treatment requires immediate intramuscular epinephrine.

Allergen-specific immunotherapy (desensitisation or subcutaneous immunotherapy, SCIT) aims to modify the immune response. Gradual escalating doses of allergen delivered subcutaneously shift the immune response from Th2 (which produces IL-4, IL-5, and IgE) towards Th1 (which produces IFN-gamma and IgG2a/b), reducing Th2 cytokine-driven symptoms. This is the only disease-modifying treatment for allergic disease.