Hypersensitivity Reactions and Allergies

Hypersensitivity Reactions or Allergies

• Pathological immune system-induced reactions to harmless antigens (allergens)
• Antigen-specific reactions

Gell and Coombs Classification of Hypersensitivity Reactions

• Type I Hypersensitivity: IgE-mediated
  • Immediate hypersensitivity or anaphylactic reaction
  • Allergic symptoms appear within 2-30 minutes after re-exposure to allergen
  • Allergen-bound IgE crosslinks FcεRI on mast cells or basophils leading to degranulation and cell activation
  • Pre-formed and activation-induced mediators cause immediate and late symptoms
  • Reaction can be local or systemic

Pre-formed Granule Mediators

• Histamine: causes vasodilation, increased vascular permeability, contraction of airway smooth muscle, mucus overproduction, and pain and itching
• Heparin: anticoagulant
• Proteases (e.g. tryptase, chymase, carboxypeptidase): tissue matrix remodeling
• Mast cells: distributed in connective tissue throughout the body, near blood and lymph vessels, skin, peritoneal cavity, gut and airway mucosa, and blood basophils (2%)

Ag Dose and Route

• Determines type and severity of symptoms

Cross-reactive Allergy Reactions

• Between pollen and foods (Oral Allergy Syndrome / Pollen-Food Allergy Syndrome)
• People allergic to birch pollen proteins develop an allergy after eating certain foods containing structurally homologous proteins

Skin Prick Test

• For detection of type I allergies
• Positive if previously sensitized mast cells loaded with allergen-specific IgE are present
• Allergen re-exposure via the skin induces degranulation
• Wheal area appears within 15-20 minutes
• Test for: food and drug allergies, pollen, mold, house dust mite, animal hair/dander, milk, wheat, fish, tree nuts, eggs, legumes, insect venoms, penicillin

Therapy of IgE-mediated Allergy

• Desensitization: Allergen-specific immunotherapy (AIT)
• Permanent desensitization to allergens (e.g. airborne)
• Intradermal administration of increasing doses of Ag for 2-3 years
• Production of IgG that binds to Ag and neutralizes it before reacting with IgE
• Based on induction of regulatory T cells (iTreg cells) that promote IgG production and suppress IgE production

Hygiene Hypothesis

• Less hygienic environment: exposure to certain infections and environmental micro-organisms during infancy and childhood leads to a general state of non-responsiveness
• Hygienic environment: children with genetic susceptibility to atopy and low exposure to infections and environmental microorganisms are more prone to developing atopic/allergic disease

Asthma Susceptibility Loci

• Genes expressed in airway epithelial cells
• Regulate differentiation and function of Th2 cells and type 2 innate lymphoid cells (ILC2)
• Genes with other or unknown functions

Hypersensitivity Type II

• IgG-mediated cytotoxic reactions
• IgG or IgM binds Ag located on the cell surface
• Cell destruction via complement activation, ADCC, and/or opsonization and phagocytosis via FcR/CR