Hypersensitivities Overview

Learning Objectives

  • Identify and compare the distinguishing characteristics, mechanisms, and major examples of type I, II, III, and IV hypersensitivities.

Clinical Focus

  • Case Study: Kerry, a 40-year-old airline pilot, experiences rashes upon sun exposure that are not sunburns. This prompts concern for potential underlying conditions triggered by her sun exposure.

Hypersensitivity Reactions Overview

  • Hypersensitivity Reactions: Undesirable reactions by the immune system classified by the immune mechanisms involved:
    • Type I: IgE-mediated reactions; allergic responses like asthma, hay fever, and anaphylaxis.
    • Type II: Cytotoxic reactions involving IgG and IgM; targets cellular antigens causing cellular damage.
    • Type III: Immune complex-mediated reactions; antibodies and soluble antigens form immune complexes leading to tissue damage.
    • Type IV: T-cell-mediated responses; involves activated macrophages and cytotoxic T-cells leading to tissue damage without the involvement of antibodies.

Type I Hypersensitivity

  • Mechanism:

    • Exposure to allergen leads to a rapid immune response upon secondary contact.
    • The IL-4 and IL-13 cytokines are secreted by T-helper cells (T2) which then stimulate B-cell differentiation and production of IgE.
    • IgE antibodies bind to mast cells, sensitizing them to future exposures.
    • Subsequent exposure results in cross-linking of IgE, leading to mast cell degranulation and the release of mediators such as histamine, leukotrienes, and cytokines.

  • Symptoms: Include mucus secretion, itching, swelling (hives), bronchoconstriction, and gastrointestinal symptoms (e.g., vomiting).

  • Localized Reactions: Hay fever, asthma, hives.

  • Systemic Reactions: Anaphylaxis, can be life-threatening with symptoms including airway obstruction and shock.

Type II Hypersensitivity

  • Mechanism: Involves IgG and IgM antibodies binding to antigens on the surface of cells, leading to cell lysis through two main mechanisms:

    • Complement Activation: Results in inflammation and lysis of target cells.
    • Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): Targeting of cells by cytotoxic T-cells.

  • Examples:

    • Hemolytic Disease of the Newborn (HDN): IgG antibodies cross the placenta causing fetal red blood cell destruction. Symptoms include anemia and edema.
    • Hemolytic Transfusion Reactions (HTR): Occurs when incompatible blood types are transfused, leading to systemic reactions including fever and potentially renal failure.

Type III Hypersensitivity

  • Mechanism: Immune complex disease involving deposition of soluble antigen-antibody complexes in tissues leading to inflammation.

    • Conditions can arise from serum sickness, autoimmune diseases, and repeated exposure to some antigens.

  • Symptoms: Widespread inflammation can cause fever, rash, and joint pain. Glomerulonephritis may develop.

  • Examples: Serum sickness, systemic lupus erythematosus (SLE).

Type IV Hypersensitivity

  • Mechanism: Primarily mediated by CD4 and CD8 T-cells rather than antibodies.
    • Types:
    1. CD4 T1-cell reactions: Delayed-type hypersensitivity (e.g., tuberculin test).
    2. CD4 T2-cell reactions: Involves chronic conditions like asthma.
    3. CD8 Cytotoxic T-lymphocyte reactions: Responsible for transplant rejection and contact dermatitis.

Diagnosis of Hypersensitivities

  • Type I Testing: Involves skin prick tests or intradermal tests to assess wheal and flare reactions. Elevated IgE levels may indicate sensitivity but require correlation with clinical history.
  • Type II and III Diagnosis: Often require clinical assessment, history, and may involve blood tests to identify specific antibodies associated with symptoms.

Treatments of Hypersensitivities

  • Desensitization Therapy: Repeated administration of allergens to train the immune system to eject a less severe response. Can be effective for insect allergies and certain food allergies.
  • Severe Reactions: Treated with epinephrine injections during anaphylaxis, with antihistamines administered post-event to reduce inflammation.
  • Type III Treatments: Involve anti-inflammatory medications and avoiding allergen exposure.

Conclusion

  • Understanding the mechanisms of hypersensitivity reactions is crucial for diagnosis, treatment, and management of allergic diseases, autoimmune disorders, and hypersensitivity reactions. Its impact spans from local allergies to systemic life-threatening conditions.