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Hypersensitivity Type I

Type I Hypersensitivity

Overview Type I hypersensitivity reactions are characterized by immediate allergic responses and mediated by IgE and Mast cell activation.

"Atopy" is the susceptibility to develop immediate hypersensitivity reactions, and is characterized by elevated levels of IgE antibodies. Atopy is influenced by genetic and environmental factors.

Pathogenesis

Primary humoral response to antigens

When Helper T cells recognize the antigen-MHC complex, intercellular interactions activate the B cell and induce production of large quantities of antigen-specific IgE antibodies.

Mast cell (aka, mastocyte) display high affinity IgE Fc receptors on their surfaces; basophils (which we haven't shown) also have high-affinity IgE receptors.

Circulating IgE antibodies readily bind these receptors, "sensitizing" the mast cell.

The next time the antigen is presented to tissues, it binds with the IgE antibodies and cross-links the mast cell receptors.

This triggers release of:

Cytoplasmic granules, which include histamines, proteases, and heparin.
Membrane phospholipids, which comprise platelet activating factor and arachidonic acid: Prostaglandin D2 and Leukotrines B4, C4, and D4.
Prostaglandin causes vasodilation and increases vascular permeability; leukotrienes recruit pro-inflammatory leukocytes and promote bronchoconstriction.
Pro-inflammatory cytokines, including Tumor Necrosis Factor (TNF), IL-1, IL-4, and chemokines.

These degranulation products mediate early and late phases of the hypersensitivity reaction.

Early Phase

Vasodilation, vascular leakage, and increased glandular secretion; notice that are the early events of the acute inflammatory response. Anti-histamines, which prevent histamine binding, are often effective at suppressing the early phase.

Late Phase

Eosinophil activity, particularly their degranulation and release of Major Basic Protein and Eosinophil Cationic Protein, among other proteins, and IL-4 and other cytokines. Broad-spectrum anti-inflammatory drugs, such as corticosteroids, can reduce eosinophilia; thus, they are more effective than anti-histamines at the late phase of type I reactions.

Skin Prick Test

Clinically, allergy diagnosis can be achieved with skin prick tests, in which small quantities of common allergens are introduced via small pricks or scratches to the skin.

In the image, we can see that this patient had positive reactions, which are characterized by wheal-like swelling and flare-like erythema, in response spiders. In contrast, there were negative responses to house dust.

Clinical Manifestations

ASTHMA

Characterized by bronchioles with thickened smooth muscle, inflamed mucosal linings with hyperactive goblet cells that fill the lumen with mucus. Upon antigen exposure, the bronchi constrict and the goblet cells are activated to secrete mucus, all of which reduces airflow.

Treatments include corticosteroids, leukotriene antagonists, and phosphodiesterase inhibitors, which suppress the inflammatory actions of the immune system.

SKIN REACTIONS

Allergic hypersensitivity can produce various skin reactions; eczema and hives are common.

Eczema (aka, atopic dermatitis) is characterized by red, scaly, flaky areas that may become "weepy;" flares can be treated with corticosteroids or topical calcineurin inhibitors, which block cytokine expression; thick emollients that maintain the skin barrier may prevent flares.

Hives are characterized by red areas with raised, swollen plaques; anti-histamines or corticosteroids are used to suppress edema and erythema.

ALLERGIC RHINITIS

Allergic rhinitis involves inflammation and stimulation of the mucosa of the nasal passages and is often associated with allergic conjunctivitis.

Anti-histamines, corticosteroids, or immunotherapy are used to suppress inflammation, and avoidance of the responsible allergens is advised.

GI ALLERGY

Gastrointestinal allergic reactions are characterized by increased smooth muscle contraction and, therefore, peristalsis and increased gastric secretions; thus, vomiting and diarrhea occur.

Aside from allergen avoidance, antihistamines to suppress smooth muscle contraction may be helpful. If the allergy is severe, anaphylaxis, which we address next, can be treated with epinephrine.

SYSTEMIC ANAPHALAXIS

Systemic anaphylaxis, which can be fatal, has multifold effects:

Bronchoconstriction, which limits airflow
Edema, which, if in the larynx, further obstructs airflow
Vasodilation, which can lead to hypotension and shock
Cardiac arrhythmia or even cardiac arrest

Immediate treatment with epinephrine, which reverses the cardiopulmonary effects, is necessary to prevent serious organ damage or death.

Common allergens

Environmental allergens include insect venom (i.e., bee stings), pollen, dust (specifically, the feces of dust mites), animal dander, and air pollution.

Foods, specifically the proteins in some foods, can trigger allergic responses; nuts, fish, milk, eggs, soy, wheat, and gluten are the most common culprits.

Medications are responsible for type I reactions; specifically, penicillin, aspirin, and other non-steroidal anti-inflammatory drugs. Paradoxically, topical corticosteroids are also known to cause allergic reactions.

Long-term desensitization

Can be achieved by regular administration of increasing quantities of the antigen, which suppresses IgE activity.

Hypersensitivity Type I

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