Immunoglobulin E (IgE)- Definition, Structure and Functions

Immunoglobulin E (IgE) is a type of antibody that belongs to the class of immunoglobulins, which are proteins produced by the immune system to fight against foreign substances such as bacteria, viruses, parasites and allergens. IgE is characterized by having an epsilon (ε) heavy chain, which distinguishes it from other classes of immunoglobulins such as IgA, IgD, IgG and IgM. IgE is present in very low concentrations in the blood serum, less than 1 microgram per milliliter (µg/mL), but it can bind to specific receptors on the surface of mast cells and basophils, which are types of white blood cells involved in inflammation and allergic reactions. When IgE binds to an antigen that it recognizes, it triggers the release of various chemical mediators from the mast cells and basophils, such as histamine, leukotrienes and cytokines, which cause the symptoms of allergic reactions such as itching, swelling, sneezing, wheezing and anaphylaxis. IgE also plays a role in immunity to certain parasites, especially helminths (worms), by coating them and facilitating their destruction by eosinophils, another type of white blood cell. IgE is produced by plasma cells, which are derived from B lymphocytes, in response to exposure to antigens. The production of IgE is regulated by several factors, such as genetic predisposition, environmental factors, infections and immunizations. The level of IgE in the blood can vary depending on the individual`s health status and exposure to allergens or parasites. High levels of IgE can indicate an allergic condition or a parasitic infection, while low levels of IgE can indicate a deficiency in the immune system or a rare genetic disorder called selective IgE deficiency.

IgE is a Y-shaped protein, made of two light chains and two heavy chains of peptides (building blocks of protein). The heavy chains form the body and arms of the Y shape, and the light chains attach just to the arms of the Y shape. A defining characteristic of IgE is the heavy chains, called epsilon (ε) chains, which have a high (12%) carbohydrate content.

The structure has two identical antigen-binding areas consisting of both light and heavy chains and valency of 2. Heavy and light chains have variable regions on their most N terminal ends. Heavy and light chains are subdivided into variable and constant regions. In addition to the disulfide bonds linking the chains together, there are intrachain disulfide links that divide each chain into areas called domains.

The light chains have two domains, one variable and one constant. The heavy chains have five domains, one variable, and four constant-region domains. It is unique in having the additional constant region (CH4). CH4 region restricts IgE binding to high-affinity receptors (Fcε-RI) on basophils and mast cells, which contain preformed granules of heparin and histamine. A hinge region is absent.

The following image shows the structure of IgE:

The function of IgE is distinct from other immunoglobulins in that it induces activation of mast cells and basophils through the cell-surface receptor Fc epsilon RI which are high-affinity receptors of The Fc region of IgE . Allergic reactions are predominantly associated with IgE. Antigen reintroduced into a previously sensitized individual binds to antigen-specific IgE on mast cells and triggers the release of the pharmacologically active agents (e.g., histamine) involved in immediate hypersensitivity syndromes such as hay fever and asthma.

IgE’s other main functions include providing immunity to parasites such as helminths like Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica . IgE is utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum . IgE may have evolved as a defense to protect against venoms.

IgE also has an essential role in type I hypersensitivity, which manifests in various allergic diseases, such as allergic asthma, most types of sinusitis, allergic rhinitis, food allergies, and specific types of chronic urticaria and atopic dermatitis. IgE also plays a pivotal role in responses to allergens, such as anaphylactic drugs, bee stings, and antigen preparations used in desensitization immunotherapy.

High IgE levels indicate that the body is overreacting to allergens leading to an allergic reaction. It can also be a sign that the body is fighting off an infection from a parasite or with some immune system conditions.

Allergic reactions are predominantly associated with IgE. Allergy is a condition in which the immune system overreacts to a harmless substance (called an allergen) and produces IgE antibodies against it. These IgE antibodies bind to specific receptors on mast cells and basophils, which are types of white blood cells that contain granules of inflammatory mediators, such as histamine. When the allergen comes in contact with the IgE-bound cells, it triggers the release of these mediators, causing various symptoms depending on the location and severity of the reaction.

Some of the common allergic reactions mediated by IgE are:

• Allergic rhinitis, or hay fever, that leads to symptoms such as runny nose, sneezing, itching, and congestion.
• Allergic conjunctivitis, or eye allergy, that causes redness, tearing, itching, and swelling of the eyes.
• Allergic asthma, a chronic inflammatory condition of the airways that results in wheezing, coughing, shortness of breath, and chest tightness.
• Atopic dermatitis, or eczema, a skin disorder characterized by dry, itchy, inflamed, and cracked skin.
• Food allergy, a reaction to certain foods or ingredients that can cause symptoms such as hives, swelling, nausea, vomiting, diarrhea, and anaphylaxis.
• Drug allergy, a hypersensitivity to certain medications that can manifest as rash, fever, joint pain, organ damage, or anaphylaxis.
• Insect sting allergy, a response to venom from bees, wasps, hornets, or fire ants that can cause pain, swelling, redness, itching, and anaphylaxis.

Anaphylaxis is a severe and potentially life-threatening allergic reaction that involves multiple organ systems and requires immediate medical attention. It can cause symptoms such as low blood pressure, rapid heartbeat, difficulty breathing, swelling of the throat or tongue, loss of consciousness, and shock.

The role of IgE in allergic reactions is not only limited to the immediate phase but also extends to the late-phase or chronic inflammatory response that occurs hours or days after the exposure to the allergen. This involves the recruitment and activation of other immune cells, such as eosinophils and lymphocytes, that produce more inflammatory mediators and cytokines. These substances can cause tissue damage and remodeling in the skin and lungs, leading to chronic conditions such as asthma and atopic dermatitis.

IgE is not only involved in allergic reactions, but also in defense against parasites, especially helminths (worms). IgE can bind to specific antigens on the surface of parasites and activate mast cells, eosinophils and basophils, which release various mediators that can damage or expel the parasites. For example, histamine can increase the permeability of blood vessels and facilitate the migration of immune cells to the site of infection, while eosinophil cationic protein can directly kill parasites by disrupting their membranes.

Some parasites, such as Schistosoma mansoni, Trichinella spiralis and Fasciola hepatica, can induce a strong IgE response in the host. This IgE response can help to limit the parasite burden and prevent tissue damage by modulating the inflammatory reaction. IgE can also enhance the phagocytosis of parasite antigens by macrophages and dendritic cells, which can present them to T cells and stimulate a protective Th2 response.

IgE may also play a role in immunity to some protozoan parasites, such as Plasmodium falciparum, which causes malaria. IgE can bind to merozoites, the invasive stage of the parasite, and inhibit their invasion of red blood cells. IgE can also activate basophils to produce IL-4 and IL-13, which can promote antibody production by B cells and inhibit pro-inflammatory cytokines by Th1 cells.

Therefore, IgE is an important component of the immune system that can help to fight off parasitic infections by various mechanisms. However, excessive or inappropriate IgE responses can also cause harmful effects, such as anaphylaxis or chronic inflammation. Thus, the regulation of IgE production and function is crucial for maintaining a balance between protection and pathology.

Type I hypersensitivity is also known as an immediate reaction and involves immunoglobulin E (IgE) mediated release of antibodies against the soluble antigen. This results in mast cell degranulation and release of histamine and other inflammatory mediators that cause vasodilation, increased capillary permeability, mucus hypersecretion, smooth muscle spasm, and tissue infiltration with eosinophils, type 2 helper T (TH2) cells, and other inflammatory cells.

Type I hypersensitivity reactions develop within minutes to hours after exposure to antigen and can affect various organs and tissues. The most common manifestations of type I hypersensitivity are allergic diseases, such as allergic asthma, rhinitis, conjunctivitis, dermatitis, urticaria, angioedema, food allergies, drug allergies, and anaphylaxis. These allergic diseases are often associated with atopy, which is an exaggerated IgE-mediated immune response to common environmental allergens.

The pathogenesis of type I hypersensitivity involves two phases: sensitization and effector. Sensitization occurs when an individual is first exposed to an antigen (allergen) and produces IgE antibodies that bind to the surface of mast cells and basophils through the high-affinity receptor Fc epsilon RI. Effector occurs when the individual is re-exposed to the same antigen and cross-links the IgE antibodies on the mast cells and basophils, triggering the release of preformed and newly synthesized mediators that cause the allergic symptoms.

The severity and type of allergic symptoms depend on several factors, such as the dose and route of antigen exposure, the distribution and density of mast cells and basophils in different tissues, the types and amounts of mediators released, and the genetic and environmental factors that modulate the immune response. Some examples of type I hypersensitivity reactions are:

• Allergic rhinitis: inflammation of the nasal mucosa caused by inhalation of allergens such as pollen, dust mites, animal dander, or mold spores. Symptoms include sneezing, nasal congestion, rhinorrhea, itching, and watery eyes.
• Allergic conjunctivitis: inflammation of the conjunctiva caused by contact with allergens such as pollen, cosmetics, or contact lenses. Symptoms include itching, redness, tearing, and swelling of the eyelids.
• Allergic asthma: inflammation of the bronchial mucosa caused by inhalation of allergens such as pollen, dust mites, animal dander, or mold spores. Symptoms include wheezing, coughing, chest tightness, shortness of breath, and airway hyperresponsiveness.
• Allergic dermatitis: inflammation of the skin caused by contact with allergens such as nickel, latex, poison ivy, or cosmetics. Symptoms include itching, erythema, edema, vesicles, and scaling.
• Urticaria: transient wheals or hives on the skin caused by various triggers such as drugs, foods, insect bites, or physical stimuli. Symptoms include itching, redness

IgE levels are normally very low in the blood, but they can increase in response to allergens or parasitic infections. High IgE levels can indicate that the body is overreacting to allergens, leading to an allergic reaction. Allergic reactions can range from mild symptoms such as sneezing, itching, and hives, to severe and life-threatening reactions such as anaphylaxis, which can cause swelling of the throat, difficulty breathing, and shock. High IgE levels can also be a sign that the body is fighting off an infection from a parasite, such as a worm or a protozoan. Parasitic infections can cause symptoms such as abdominal pain, diarrhea, fever, and skin rashes. High IgE levels can also be associated with some immune system conditions, such as atopic dermatitis, asthma, chronic urticaria, and allergic bronchopulmonary aspergillosis. These conditions are characterized by chronic inflammation and hypersensitivity to various environmental triggers.

High IgE levels can be measured by a blood test called serum total IgE test. This test measures the amount of IgE in the blood. However, this test does not identify the specific allergen or parasite that is causing the high IgE level. To determine the cause of high IgE level, other tests may be needed, such as skin prick test, patch test, allergen-specific IgE test, stool test, or biopsy. These tests can help identify the specific substance or organism that is triggering the immune response.

High IgE levels can be treated by avoiding the allergen or parasite that is causing the reaction. This may involve avoiding certain foods, animals, plants, or medications that are known to trigger allergies. It may also involve taking anti-parasitic drugs to kill the infection. In some cases, immunotherapy may be used to reduce the sensitivity to the allergen or parasite. Immunotherapy involves exposing the body to small and gradually increasing doses of the allergen or parasite over a period of time. This can help desensitize the immune system and prevent severe reactions in the future.

High IgE levels can have a significant impact on the quality of life of affected individuals. They can cause discomfort, distress, and impairment in daily activities. They can also increase the risk of complications such as infections, organ damage, and anaphylaxis. Therefore, it is important to monitor and manage high IgE levels with appropriate diagnosis and treatment.

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