Hypersensitivities Overview

Hypersensitivity Overview

  • Definition: Hypersensitivities are an altered immunological response to an antigen that results in disease or damage to the host.
  • Antigen Meaning: An antigen is an "antibody generator"; it is something foreign that the body recognizes.
  • Sensitization: Involves an adequate amount of antibodies or T cells that cause noticeable physical symptoms and reactions when encountering the antigen.

Types of Hypersensitivity

Immediate vs. Delayed Hypersensitivity
  • Immediate Hypersensitivity: Occurs within minutes to a few hours after exposure (e.g., peanut allergies). Examples include:
    • Anaphylaxis - severe allergic reaction requiring epinephrine.
  • Delayed Hypersensitivity: Symptoms occur after a delay (hours to days) (e.g., contact dermatitis).
Four Main Types of Hypersensitivity

  1. Type 1: IgE-Mediated

    • Mechanism: Involves IgE antibodies and mast cells that degranulate, releasing histamine and other mediators causing potent inflammatory responses.
    • Common Conditions: Allergic rhinitis, allergic conjunctivitis, hives, atopic eczema, soft tissue angioedema, severe allergic asthma, and peanut allergies.
    • Statistics: Type 1 allergies are rising in the US with 20-30% of the population affected.

  2. Type 2: Tissue-Specific

    • Mechanism: Involves IgG and IgM antibodies leading to the destruction of host tissues. Can activate complement system or lead to cytotoxic cellular responses.
    • Examples:
      • Heparin-induced thrombocytopenia
      • Hemolytic anemia post-drug administration
      • Myasthenia gravis (destruction of acetylcholine receptors)
      • Graves' disease (thyroid tissue destruction)
      • Graft versus host disease.

  3. Type 3: Immune Complex-Mediated

    • Mechanism: Involves the formation of antigen-antibody complexes that can deposit in tissues, activating complement and recruiting leukocytes, causing inflammation and tissue damage.
    • Examples:
      • Serum sickness
      • Hypersensitivity pneumonia
      • Systemic lupus erythematosus (SLE)
      • Post-streptococcal glomerulonephritis.

  4. Type 4: Cell-Mediated

    • Mechanism: Involves T cells, specifically memory T cells, and does not involve antibodies. Cytokines released lead to inflammation and tissue damage.
    • Examples:
      • Contact dermatitis (e.g., nickel allergy)
      • Poison ivy
      • TB skin testing
      • Acute graft rejection.

Prevalence and Relevance of Hypersensitivities

  • Common occurrence recognized in the population, with 10-20% of drug reactions being classified as hypersensitivities.
  • 3-7% of hospitalized patients may experience hypersensitivity reactions.

Genetic Factors

  • Hypersensitivities are not single-gene diseases but rather multifactorial with genetic components potentially increasing risks, especially in atopic conditions.
  • E.g., if one parent has allergies, the risk of children developing them is about 40%, and up to 80% if both parents are affected.

Type 1 Hypersensitivity Details

  • Antibody: IgE antibody | Immediate Reaction | Mast Cells: Release histamine leading to:
    • Effects: Bronchial constriction, vascular permeability, smooth muscle contraction, and edema.
    • Examples: Allergic rhinitis, asthma, food allergies (e.g., shellfish, peanuts).

Type 2 Hypersensitivity Details

  • Mechanisms: Complement activation, cytotoxicity mediated by IgG/IgM, phagocytosis of antibody-coated cells.
    • Examples: Hemolytic anemia, myasthenia gravis (autoantibodies to acetylcholine receptors).

Type 3 Hypersensitivity Details

  • Mechanisms: Formation of immune complexes leading to localized tissue damage.
    • Examples: Systemic lupus erythematosus, post-streptococcal glomerulonephritis.

Type 4 Hypersensitivity Details

  • Mechanisms: Direct tissue damage by T cells (CD4 and CD8).
    • Examples: Contact dermatitis, graft rejection.

Evaluation of Hypersensitivities

  • Type 1 evaluations often include IgE testing, skin prick tests.
  • Type 2 & 3 evaluations may involve antibody panels; Type 4 is typically diagnosed through patient history or skin testing.

Management Strategies

  • Type 1: Desensitization programs, avoidance of allergens, medications (antihistamines, corticosteroids, epinephrine for anaphylaxis).
  • Type 2 & 3: Avoid offending agents, supportive care.
  • Type 4: Avoid allergens, corticosteroids for inflammation, JAK inhibitors for T cell activation.

Prognosis

  • Childhood allergies may resolve over time but cannot be guaranteed as many factors influence the persistence of allergies.
  • Regular monitoring of IgE levels and potential rechallenge may be considered as the child develops.