Type I Hypersensitivity Reaction

Type I hypersensitivity reaction is an abnormal immune response triggered by exposure to specific antigens known as allergens. In this type of hypersensitivity reaction, the presentation of the antigen to the T-helper cells (Th cells) initiates a cascade of immunologic events leading to the production of antigen-specific IgE antibodies. Reexposure to the antigen promotes degranulation of the IgE-bound mast cells and basophils, releasing chemical mediators that cause various allergy symptoms. Manifestations can be local, depending on the route of entry of the antigen. In severe cases, systemic reaction leads to anaphylactic shock. To determine allergic etiology, skin testing as well as in vitro tests are available. Management includes avoidance of triggers to reduce exacerbation. Common treatment options are antihistamines and glucocorticoids to control the inflammatory response. Anaphylaxis, however, is a medical emergency that requires immediate airway access with administration of epinephrine and fluid resuscitation.

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  • Immune system
    • An integral system of cells and their products that recognizes, attacks, and destroys potentially harmful entities to the health of an individual
    • Provides normal protective immune response against pathogens
  •  Hypersensitivity reaction
    • A “hyper” or exaggerated immune response to what should be seen as harmless environmental antigens
    • Types I, II, and III are immediate reactions occurring within 24 hours.
    • Type IV reaction develops over several days.
  • Type I hypersensitivity reaction (atopy/type I immediate hypersensitivity reaction): involves immunoglobulin E (IgE)-mediated mast cell and basophil degranulation on reexposure to an antigen
  • Allergy: an abnormal adaptive immune response that may or may not involve antigen-specific IgE

Epidemiology and Etiology


  • Lifetime prevalence: 15% worldwide
  • In the United States: 
    • Allergies are the 6th-leading cause of chronic illness.
    • Asthma, a form of airway hyperresponsiveness, accounts for over 500,000 hospitalizations each year.
  • Allergic diseases have increased over the past half-century, partly from lifestyle changes (improved hygiene → reduced exposure to allergens early in life) and pollution.


  • Genetic predisposition:
    • No single dominant gene for allergy
    • Certain genes involved in the specific immune response (FcεR1 [high-affinity IgE receptor], IL-4 [interleukin 4], and other cytokines; CD14 [cluster of differentiation 14], HLA-DR [human leukocyte antigen-DR], Th1/Th2 [T-helper 1 and 2 cells] differentiation) contribute to the development of allergies.
  • Environment:
    • Allergen exposure
    • Increased air pollution
    • Bacterial and viral infection
    • Lifestyle: nutrition, hygiene, pet ownership


Sensitization stage

  • Asymptomatic; 1st antigen exposure
  • Allergen is recognized by antigen-presenting cells presented to naive T cells → T cells differentiate into Th2 cells
  • Th2 cells release interleukins (IL-4, IL-5IL-13) → switches B cells to increase IgE antibody production → IgE antibodies bind to mast cells and basophils (via FcεRI receptors)

Reaction or effector stage

  • Mast cells and basophils are now bound with antigen-specific IgE antibodies ready to respond on antigen re-exposure. 
  • Early-phase reaction:
    • Occurs within minutes
    • May be a local or systemic reaction 
    • IgE-bound mast cell and basophil degranulation releasing mediators cause symptoms
      • Histamine: vasodilation, bronchial smooth muscle contraction, increased mucus secretion, increased vessel permeability
      • Prostaglandin: pulmonary smooth muscle contraction, platelet aggregation
      • Platelet-activating factor: platelet aggregation, vasodilation
      • Leukotrienes: bronchial smooth muscle contraction, increased vessel permeability, mucus production  
  • Late-phase reaction:
    •  Occurs 412 hours later, peaking at 69 hours
    • Eosinophils (predominant) and other leukocytes migrate to allergen-contaminated tissue


  • Drugs (most commonly) (e.g., penicillin, cephalosporins,  muscle relaxants, anesthetics)
    • Medications cause the most allergy-related deaths.
  • Food (e.g., nuts, shellfish, eggs, soy, wheat, cow’s milk)
  • Insect venom (e.g., bee and wasp venom)
  • Environmental allergens (e.g., dust mites, animal dander, pollen, grass, latex)
Type i anaphylactic hypersensitivity

Pathophysiology of type 1 hypersensitivity:
1. Antigen-presenting cells (APC) recognize the allergen and presents to naive T cells
2. T cells differentiate into Th2 which release the interleukins.
3. Interleukins stimulate the B cells to produce IgE.
4. Antigen-specific IgE binds to mast cells and basophils.
5. Subsequent exposure to the same antigen leads to degranulation and release of mediators.

TCR: T cell receptor

Image by Lecturio.
Mast cells in allergy

Mast cells are involved in allergy. Allergies such as pollen allergy are related to the antibody known as IgE. Like other antibodies, each IgE antibody is specific; one acts against oak pollen, another against ragweed.

Image by Lecturio.

Types of hypersensitivity

Table: Comparison of type I hypersensitivity to other types of hypersensitivity
Type I Type II Type III Type IV
IgE-mediated hypersensitivity IgG-mediated cytotoxic hypersensitivity Immune complex-mediated hypersensitivity Cell-mediated hypersensitivity
IgE is bound to mast cells via its fragment crystallizable (Fc) portion. When an allergen binds to these antibodies, crosslinking of IgE induces degranulation. Cells are destroyed by bound antibody, either by activation of complement or by a cytotoxic T cell with an Fc receptor for the antibody (antibody-dependent cellular cytotoxicity). Antigen-antibody complexes are deposited in tissues, causing activation of complement, which attracts neutrophils to the site. Th1 cells secrete cytokines, which activate macrophages and cytotoxic T cells and can cause macrophage accumulation at the site.
Causes localized and systemic anaphylaxis; seasonal allergies including hay fever; food allergies, such as those to shellfish and peanuts; hives; and eczema. Red blood cells are destroyed by complement and antibody during a transfusion of mismatched type or during erythroblastosis fetalis. The most common forms of immune complex disease include glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus. The most common forms are contact dermatitis, tuberculin reaction, diabetes mellitus type I, multiple sclerosis, and rheumatoid arthritis.
Source: Schatz, Phil. Diseases Associated with Depressed or Overactive Immune Responses. Anatomy and Physiology. Retrieved August 21, 2020, from https://philschatz.com/anatomy-book/contents/m46566.html

Clinical Features

Localized allergic reaction

  • Rashes or blisters in the skin, pruritus (hives, atopic dermatitis, eczema)
  • Increased eye and nasal secretions, itching, sneezing (allergic rhinitis/hay fever, allergic conjunctivitis)
  • Oropharyngeal mucosal edema (food allergies)
  • Bronchospasm, wheezing (bronchial asthma)
  • Gastrointestinal abnormalities such as abdominal pain, diarrhea, vomiting (food allergies)

Systemic reaction/anaphylaxis

  • Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction occurring within minutes of exposure to an allergen.
  • A medical emergency: fatal without immediate treatment!
  • Rapid in onset but the course can be biphasic (symptoms seem to resolve then return 13 hours later with the same severity)
  • Large quantities of inflammatory mediators released → rapid systemic vasodilation and vascular permeability → hypotension and extensive tissue edema → fluid in the lungs and constriction of airways → shortness of breath and lethal suffocation → cardiovascular collapse and loss of consciousness
  • Treatment: immediate administration of epinephrine to reverse bronchoconstriction and vasodilation
Anaphylactic symptoms Effects of histamine
Rhinitis, conjunctivitis Peripheral vasodilation, increased vascular permeability, increased mucus secretion
Erythema Accumulation of blood in the capillary bed from vasodilation
Pulmonary edema, angioedema, hypotension Fluid shift into the stroma from increased vessel permeability, vasodilation
Pruritus, urticaria, or hives Fluid extravasation into dermis; increase trigger of skin sensory nerves (itch)
Bronchospasm, bronchoconstriction Bronchial smooth muscle contraction, increased mucus secretion


Skin testing

  • Advantages:
    • Results available within 1520 minutes
    • Less costly
    • Patients can see the reactions, which helps them understand their allergies.
  • Contraindications:
    • Recent anaphylactic event 
    • Medications that may interfere with testing (e.g., H1 and H2 blockers, tricyclic antidepressants, prednisone) or treatment of anaphylaxis (e.g., beta-blockers) 
    • Individuals with high risk of anaphylaxis (history of immediate anaphylaxis, uncontrolled asthma, significant cardiovascular disease, frail elderly, pregnant)
  • Test methods:
    • Skin prick test (positive test is a wheal ≥ associated histamine control or > 3 mm)
    • Scratch test (rarely used)
    • Intradermal method: injection of allergen into skin

In vitro testing

  • Advantages:
    • Does not pose a risk of allergic reaction, so suitable for high-risk individuals 
    • Not affected by patient medications
    • Not reliant on skin condition
  • Disadvantages:
    • Expensive
    • In case of total IgE level, low or normal levels do not exclude allergy status; inciting allergen is also not specified.
  • Tests:
    • Immunoassays for allergen-specific IgE: available for food, insect venom, environmental allergen, latex, drugs
    • Total IgE level: Patients with allergic conditions often have higher levels, but the result does not indicate to which specific allergen.


Localized reaction

  • Avoid triggering allergen
  • Patients need to wear a MedicAlert bracelet that notes the possibility of anaphylaxis.
  • Therapeutic options:
    • H1 blockers/antihistamines 
    • Inhaled bronchodilators (albuterol) and inhaled corticosteroids for asthma
    • Intranasal glucocorticoids or intranasal mast cell stabilizer for allergic rhinitis
    • Vasoconstrictor/antihistamine ophthalmic drops for allergic conjunctivitis (for short-term or episodic use)
    • Oral glucocorticoids for systemic symptoms of an allergic reaction/asthma (for short-term use)
    • Leukotriene receptor antagonist (montelukast) for asthma and allergic rhinitis
    • Anti-IgE immunotherapy (omalizumab) for severe asthma
  • Allergy immunotherapy (AIT)
    • Desensitization or hypo-sensitization
    • Subcutaneous or sublingual delivery
    • Alters abnormal immune response
    • Highly effective for allergic rhinitis/conjunctivitis and allergic asthma


  • Epinephrine 0.30.5 mg intramuscularly
    • Dose can be repeated
    • Decreases mortality rates significantly!
  • Immediate intubation for impending airway obstruction
  • If not intubated: oxygen support via facemask up to 10 L/min 
  • Intravenous fluids
  • Albuterol inhalation for bronchospasm
  • Refractory symptoms:
    • Can add an inotropic agent (dopamine, norepinephrine) 
    • Atropine for any bradycardic episodes
    • Glucagon for patients on beta-blockers who may not respond to epinephrine
  • Adjunctive treatments:
    • H1- and H2-receptor blockers 
      • Histamine antagonists
      • H2-receptor blockers (decrease stomach acid production) potentiate effect of H1-receptor blockers
    • Corticosteroid infusion

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