24.7: Allergic Reactions

We speak of an allergy when the immune system triggers a response against a benign foreign structure, like food, pollen or pet dander. These elicitors are called allergens. If the immune system of a hypersensitive individual was primed against a specific allergen, it will trigger allergic symptoms during every subsequent encounter of the allergen. Symptoms can be mild, such as hay fever, to severe, such as potentially fatal anaphylactic shock.

Sensitization Is the First Step of an Allergy

The immune system is crucial for defending an organism against bacteria, viruses, fungi, toxins, and parasites. However, in a hypersensitive response, it can be triggered by harmless substances and cause unpleasant or potentially life-threatening overreactions, called allergies. The first step toward establishing an allergy is sensitization. For instance, an individual becomes allergic to the pollen of ragweed when, for the first time, immune cells in the respiratory passage take up the pollen and degrade the allergens into fragments. These immune cells are called antigen-presenting cells, or APCs, because they display the degraded allergen fragments on their surface. Examples of APCs are dendritic cells, macrophages and B cells.

Subsequently, APCs activate encountered Type 2 helper T cells (T_h2). The activated T_h2 then release chemical signals (e.g., cytokines) that cause B cells to differentiate into antibody-producing plasma cells. Plasma cells, in turn, produce immunoglobulin E (IgE), a class of antibodies.

Once created, IgE binds to the surface of mast cells. Mast cells are especially prevalent in tissues that separate the outside and inside of an organism, such as the skin, mucosa of the lungs, digestive tract, mouth, and nose. The binding of IgE to the mast cells finalizes sensitization.

Repeated Allergen Exposure Induces an Inappropriate Immune Response

The next time the body encounters ragweed pollen, the IgE stimulates the mast cells to produce inflammatory chemicals, such as histamines, leukotrienes, and cytokines. These chemicals produce the typical allergic symptoms of hay fever: sneezing, runny nose, and nasal passage inflammation. Allergen exposure also causes mast cells and T_h2 to release chemical signals that recruit and activate other inflammation-inducing immune cells, such as eosinophils and basophils, further amplifying symptoms.

The IgE that have been produced in response to ragweed pollen during sensitization are specific to ragweed. This means that these IgE will trigger an immune response (i.e., allergic reaction) whenever they encounter ragweed pollen. In some cases, the ragweed pollen-specific IgE might also trigger an allergic reaction in response to other allergens. This process is called cross-reactivity.

An Anaphylactic Shock Is a Potentially Fatal Systemic Allergic Reaction

While some allergic episodes may present merely a nuisance, others have potentially fatal consequences if not treated quickly. Although the prevalence of anaphylaxis varies regionally, an estimated 0.05-2% of people suffer from an anaphylactic shock—the rapid onset of a systemic allergic response. Triggers can be food, medication, latex, and venom from insects. Within minutes of allergen exposure, mast cells release a large number of mediators into the bloodstream. The mediators, such as histamines, leukotrienes, and tryptase, lead to restriction of airways (bronchoconstriction), widening of blood vessels (vasodilation), increased mucus production, changes in heart rate, and vascular permeability.

To diagnose anaphylaxis, one should, therefore, look for rashes, a rapid increase of mucus, difficulty breathing, reduced blood pressure and gastrointestinal symptoms over a time course ranging from several minutes to hours after allergen exposure. Epinephrine is the only potent medication known to counteract the complex physiological changes during anaphylaxis. It initiates constriction of blood vessels, increases heart rate, stabilizes heart contractility, and increases airflow through the airways. Epinephrine is usually auto-applied using an EpiPen, as a fast response after the onset of anaphylaxis is critical.

An allergy is a hypersensitive immune response to a normally harmless substance. The first process necessary for establishing an allergy is sensitization.

For example, individuals who are allergic to grass pollen have undergone sensitization. Their immune cells lining the respiratory passage take up and degrade the allergens into fragments.

These immune cells are called antigen presenting cells, or APCs because they display the degraded allergen fragments on their surface.

The APCs activate another encountered cell, type two T helper cells, abbreviated as Th2.

The activated Th2 then release chemical signals that cause another type of immune cell, B cells, to develop into antibody producing plasma cells which make immunoglobulin E, or IgE, a class of antibodies.

In this case, exposure to grass pollen will produce an IgE specific to this pollen, causing an allergic reaction distinct to grass pollen and no other type.

Once created, IgE binds to the surface of specialized cells called mast cells, found in tissues like the mucous membranes and skin.

Following sensitization, an allergic reaction occurs each time an individual encounters the allergen to which they are allergic after the allergen binds to its specific IgE on mast cells.

For instance, when the grass pollen allergen binds to its IgE, it causes the release of allergy symptom causing chemicals, such as leukotrienes and histamines that lead to sneezing, runny noses, and nasal passage inflammation.

Allergen exposure also causes mast cells and Th2 to release chemical signals that recruit and activate other inflammation inducing immune cells such as eosinophils and basophils to further amplify symptoms.