Hypersensitivity and Type I Allergies

Hypersensitivity

• An exaggerated response to a typically harmless antigen that results in tissue injury, disease, or even death.
• Gell and Coombs classified hypersensitivity reactions into four types based on the immunologic mechanism involved, the antibody, and the nature of the triggering antigen.
  • Antibody-mediated: Type I, II, and III
  • Cell-mediated: Type IV

Type I Hypersensitivity

• Commonly referred as allergies
• The antigens that trigger type I hypersensitivities are called allergens.
• Distinguishing features: Short time lag phase.
• Key Immunologic Components:
  • IgE
  • Basophils
  • Mast cells
  • Eosinophils

Type I Hypersensitivity Reaction

• Immune Mediator: IgE
• Synonym: Anaphylactic
• Timing: Immediate
• Antigen: Heterologous
• Complement Involvement: No
• Immune Mechanism: Release of mediators from IgE-sensitized mast cells and basophils.
• Clinical Examples:
  • Anaphylaxis
  • Allergic Rhinitis
  • Allergic Asthma
  • Food Allergies
  • Urticaria

Tests for Type I Hypersensitivity

• In Vivo Skin Prick Test:
  • Preferred screening test for allergies.
  • Very small amounts of potential allergens are injected under the skin.
  • Positive result: Wheal-and-flare reaction after 20 minutes.
• Radioallergosorbent Test (RAST):
  • A form of radioimmunoassay.
  • A form of allergen-specific IgE testing.
• Radioimmunosorbent Test (RIST):
  • First test developed for the measurement of total IgE.

Type II Hypersensitivity

• Also known as antibody-mediated cytotoxic hypersensitivity.
• Involves IgG and IgM antibodies directed against antigens found on cell surfaces.

Type II Hypersensitivity Reaction

• Immune Mediator: IgG or IgM.
• Synonym: Antibody-mediated cytotoxicity.
• Timing: Immediate.
• Antigen: Autologous or heterologous, found on the cell surface.
• Complement Involvement: Yes.
• Immune Mechanism: Cell destruction caused by antibody and complement, opsonization, ADCC. Cell function inhibited by antibody binding.
• Clinical Examples:
  • Transfusion reactions
  • Autoimmune hemolytic anemia
  • Hemolytic disease of the newborn
  • Drug reactions
  • Myasthenia gravis
  • Goodpasture's syndrome
  • Graves' disease

Type III Hypersensitivity

• Also known as immune complex hypersensitivity.
• Similar to Type II, but antigens are soluble.

Type III Hypersensitivity Reaction

• Immune Mediator: IgG or IgM.
• Synonym: Complex-mediated.
• Timing: Immediate.
• Antigen: Soluble, heterologous or autologous.
• Complement Involvement: Yes.
• Immune Mechanism: Antigen-antibody complex activates complement proteins. Neutrophils are recruited and release lysosomal enzymes causing tissue damage.
• Clinical Examples:
  • Serum sickness
  • Arthus reaction
  • Lupus erythematosus
  • Rheumatoid arthritis
  • Drug reactions

Arthus Reaction

• Immune complexes formed deposit on the walls of blood vessels, activating complement.

Serum Sickness

• Results from passive immunization of humans with animal serum.
• Humans develop antibodies against protein in the animal serum, antibodies combine with the protein forming complexes that can deposit in the tissues.

Type IV Hypersensitivity

• First described by Robert Koch.
• Sensitized T cells, rather than antibodies, play a major role.
• Also known as delayed hypersensitivity because symptoms peak between 48-72 hours.