13.2 Allergic responses and IgE-mediated immunity

Allergies are a common immune system overreaction to harmless substances. IgE antibodies, produced by B cells, play a crucial role in allergic responses by binding to mast cells and basophils, priming them for future reactions.

When allergens enter the body, they trigger a complex process of sensitization and re-exposure. This leads to the release of inflammatory mediators like histamine and leukotrienes, causing symptoms ranging from mild discomfort to life-threatening anaphylaxis.

IgE-Mediated Allergic Responses

Role of IgE antibodies

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• IgE antibodies drive allergic responses produced by B cells upon allergen exposure
• Bind to high-affinity Fc receptors (FcεRI) on mast cells and basophils priming for future reactions
• IgE-mediated sensitization occurs during initial allergen contact triggering IgE production
• Cross-linking of IgE in subsequent exposures activates mast cells and basophils releasing inflammatory mediators (histamine, leukotrienes)

Process of allergic sensitization

• Sensitization phase:

1. Allergen enters body
2. Antigen-presenting cells process and present allergen to T cells
3. T cells stimulate B cells to produce IgE antibodies
4. IgE antibodies bind to mast cells and basophils

• Re-exposure phase:

1. Allergen binds to IgE on sensitized cells
2. Cross-linking of IgE molecules occurs
3. Rapid degranulation of mast cells and basophils
4. Release of preformed mediators (histamine)
5. Synthesis and release of newly formed mediators (leukotrienes, prostaglandins)

Function of cells in allergies

• Mast cells reside in connective tissue and mucosal surfaces triggering immediate allergic reactions
• Basophils circulate in blood contributing to systemic allergic responses
• Mediators and their effects:
  • Histamine causes vasodilation, increased vascular permeability, bronchoconstriction
  • Leukotrienes induce prolonged bronchoconstriction, increased vascular permeability
  • Prostaglandins lead to vasodilation, pain sensitization
  • Cytokines recruit and activate inflammatory cells (eosinophils, neutrophils)

Allergens and Hypersensitivity Reactions

Common allergens and symptoms

• Allergens:
  • Pollen triggers hay fever, allergic rhinitis (ragweed, birch)
  • Dust mites exacerbate asthma, eczema
  • Animal dander causes allergic rhinitis, asthma (cats, dogs)
  • Food allergens induce gastrointestinal symptoms, anaphylaxis (peanuts, shellfish)
  • Insect venom results in localized swelling, anaphylaxis (bees, wasps)
• Symptoms:
  • Respiratory issues manifest as sneezing, coughing, wheezing, shortness of breath
  • Skin reactions include itching, hives, eczema
  • Gastrointestinal distress presents as nausea, vomiting, diarrhea
  • Cardiovascular symptoms involve hypotension, tachycardia in severe reactions
  • Anaphylaxis affects multiple organ systems simultaneously

Immediate vs delayed hypersensitivity

• Immediate hypersensitivity (Type I):
  • IgE-mediated response
  • Rapid onset within minutes to hours
  • Involves mast cells and basophils
  • Examples: hay fever, asthma, anaphylaxis
• Delayed-type hypersensitivity (Type IV):
  • T cell-mediated reaction
  • Delayed onset 24-72 hours after exposure
  • Involves T cells and macrophages
  • Examples: contact dermatitis, chronic asthma
• Key differences:
  • Time course of reaction varies significantly
  • Cellular mechanisms differ (IgE vs T cells)
  • Types of mediators released change (histamine vs cytokines)
  • Clinical manifestations and treatments vary based on reaction type