Type I hypersensitivity | |
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Other names | Immediate hypersensitivity |
Image showing the mechanism of activation of type 1 hypersensitivity in a mast cell. | |
Specialty | Immunology |
Type I hypersensitivity (or immediate hypersensitivity), in the Gell and Coombs classification of allergic reactions, is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. [1] Type I is distinct from type II, type III and type IV hypersensitivities. The relevance of the Gell and Coombs classification of allergic reactions has been questioned in the modern-day understanding of allergy, and it has limited utility in clinical practice. [2]
Exposure may be by ingestion, inhalation, injection, or direct contact.
In type I hypersensitivity, B cells are stimulated (by CD4+ Th2 cells) to produce IgE antibodies specific to an antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that in type 1 hypersensitivity, the antibody is IgE instead of IgA, IgG, or IgM. During sensitization, the IgE antibodies bind to FcεRI receptors on the surface of tissue mast cells and blood basophils. [3] Mast cells and basophils coated by IgE antibodies are "sensitized". Later exposure to the same allergen cross-links the bound IgE on sensitized cells, resulting in anaphylactic degranulation, which is the immediate and explosive release of pharmacologically active pre-formed mediators from storage granules and concurrent synthesis of inflammatory lipid mediators from arachidonic acid; [4] some of these mediators include histamine, leukotriene (LTC4 and LTD4 and LTB4), and prostaglandin, which act on proteins (e.g., G-protein coupled receptors) located on surrounding tissues. [4] The principal effects of these products are vasodilation and smooth-muscle contraction.
Type I hypersensitivity can be further classified into immediate and late-phase reactions. Within minutes of exposure to an antigen, the immediate hypersensitivity occurs, releasing histamines and lipid mediators which are responsible for the initial allergic reaction response. However, about 4-12 hours after antigen exposure, a cough and wheezing may persist in the patient, along with swelling and redness of the skin. This is known as the late-phase hypersensitivity reaction which can last from approximately 1-3 days and is caused by the release of additional mediators from the mast cells and basophils. [5]
Vasodilation and increased permeability | ||
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Smooth muscle spasm |
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Leukocyte extravasation |
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Unless otherwise specified, the reference for this table is: [6] |
The reaction may be either local or systemic. Symptoms vary from mild irritation to sudden death from anaphylactic shock.
If multiple systems are involved, then anaphylaxis can take place, which is an acute, systemic reaction that can prove fatal.
Treatment usually involves adrenaline (epinephrine) because it counteracts anaphylaxis by increasing blood flow and relaxing bronchial muscles that block one’s airways. [7] Antihistamines and corticosteroids are also commonly used in less severe reactions. [8]
Some examples:
Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, allergic asthma, and anaphylaxis. Symptoms may include red eyes, an itchy rash, sneezing, coughing, a runny nose, shortness of breath, or swelling. Note that food intolerances and food poisoning are separate conditions.
Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the following: an itchy rash, throat closing due to swelling that can obstruct or stop breathing; severe tongue swelling that can also interfere with or stop breathing; shortness of breath, vomiting, lightheadedness, loss of consciousness, low blood pressure, and medical shock. These symptoms typically start in minutes to hours and then increase very rapidly to life-threatening levels. Urgent medical treatment is required to prevent serious harm and death, even if the patient has used an epipen or has taken other medications in response, and even if symptoms appear to be improving.
A mast cell is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumors.
Hypersensitivity is an abnormal physiological condition in which there is an undesirable and adverse immune response to antigen. It is an abnormality in the immune system that causes immune diseases including allergies and autoimmunity. It is caused by many types of particles and substances from the external environment or from within the body that are recognized by the immune cells as antigens. The immune reactions are usually referred to as an over-reaction of the immune system and they are often damaging and uncomfortable.
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte and how they work is not fully understood. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, and heparin that prevents blood clotting, although there are less than that found in mast cell granules. Mast cells were once thought to be basophils that migrated from the blood into their resident tissues, but they are now known to be different types of cells.
Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.
A food allergy is an abnormal immune response to food. The symptoms of the allergic reaction may range from mild to severe. They may include itchiness, swelling of the tongue, vomiting, diarrhea, hives, trouble breathing, or low blood pressure. This typically occurs within minutes to several hours of exposure. When the symptoms are severe, it is known as anaphylaxis. A food intolerance and food poisoning are separate conditions, not due to an immune response.
Omalizumab, sold under the brand name Xolair, is an injectable medication to treat severe persistent allergic forms of asthma, nasal polyps, urticaria (hives), and immunoglobulin E-mediated food allergy.
The high-affinity IgE receptor, also known as FcεRI, or Fc epsilon RI, is the high-affinity receptor for the Fc region of immunoglobulin E (IgE), an antibody isotype involved in allergy disorders and parasite immunity. FcεRI is a tetrameric receptor complex that binds Fc portion of the ε heavy chain of IgE. It consists of one alpha, one beta, and two gamma chains connected by two disulfide bridges on mast cells and basophils. It lacks the beta subunit on other cells. It is constitutively expressed on mast cells and basophils and is inducible in eosinophils.
Allergic inflammation is an important pathophysiological feature of several disabilities or medical conditions including allergic asthma, atopic dermatitis, allergic rhinitis and several ocular allergic diseases. Allergic reactions may generally be divided into two components; the early phase reaction, and the late phase reaction. While the contribution to the development of symptoms from each of the phases varies greatly between diseases, both are usually present and provide us a framework for understanding allergic disease.
Talizumab (TNX-901) is a humanized monoclonal antibody that was under development by Tanox in Houston, Texas as a new-concept therapeutic for allergic diseases. The unique anti-IgE antibody was designed to target immunoglobulin E (IgE) and IgE-expressing B lymphocytes specifically, without binding to IgE already bound by the high affinity IgE receptors on mast cells and basophils. Talizumab was tested in clinical trials at National Jewish Medical and Research Center and other medical centers and allergy clinics across the U. S. and shown to be able to prevent allergic reactions to accidental exposure to peanuts, which is contained in many kinds of foods.
A drug allergy is an allergy to a drug, most commonly a medication, and is a form of adverse drug reaction. Medical attention should be sought immediately if an allergic reaction is suspected.
Type II hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an antibody mediated process in which IgG and IgM antibodies are directed against antigens on cells or extracellular material. This subsequently leads to cell lysis, tissue damage or loss of function through mechanisms such as
Type III hypersensitivity, in the Gell and Coombs classification of allergic reactions, occurs when there is accumulation of immune complexes that have not been adequately cleared by innate immune cells, giving rise to an inflammatory response and attraction of leukocytes. There are three steps that lead to this response. The first step is immune complex formation, which involves the binding of antigens to antibodies to form mobile immune complexes. The second step is immune complex deposition, during which the complexes leave the plasma and are deposited into tissues. Finally, the third step is the inflammatory reaction, during which the classical pathway is activated and macrophages and neutrophils are recruited to the affected tissues. Such reactions may progress to immune complex diseases.
Allergic symptoms are caused by an initial systemic histamine release by activated basophils and mast cells, that may lead to shock with laryngeal edema, lower-airway obstruction and hypotension. This is why basophils are considered with mast cells to be the key cells in allergic diseases.
Pseudoallergy, sometimes known as nonallergic hypersensitivity, is a clinical mimic of immediate-type allergic reactions that lacks underlying immunological mechanisms.
Kounis syndrome is defined as acute coronary syndrome caused by an allergic reaction or a strong immune reaction to a drug or other substance. It is a rare syndrome with authentic cases reported in 130 males and 45 females, as reviewed in 2017; however, the disorder is suspected of being commonly overlooked and therefore much more prevalent. Mast cell activation and release of inflammatory cytokines as well as other inflammatory agents from the reaction leads to spasm of the arteries leading to the heart muscle or a plaque breaking free and blocking one or more of those arteries.
Fish allergy is an immune hypersensitivity to proteins found in fish. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anaphylaxis, a potentially life-threatening condition which requires treatment with epinephrine. Other presentations may include atopic dermatitis or inflammation of the esophagus. Fish is one of the eight common food allergens which are responsible for 90% of allergic reactions to foods: cow's milk, eggs, wheat, shellfish, peanuts, tree nuts, fish, and soy beans.
Shellfish allergy is among the most common food allergies. "Shellfish" is a colloquial and fisheries term for aquatic invertebrates used as food, including various species of molluscs such as clams, mussels, oysters and scallops, crustaceans such as shrimp, lobsters and crabs, and cephalopods such as squid and octopus. Shellfish allergy is an immune hypersensitivity to proteins found in shellfish. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anaphylaxis, a potentially life-threatening condition which requires treatment with epinephrine. Other presentations may include atopic dermatitis or inflammation of the esophagus. Shellfish is one of the eight common food allergens, responsible for 90% of allergic reactions to foods: cow's milk, eggs, wheat, shellfish, peanuts, tree nuts, fish, and soy beans.
A food allergy to sesame seeds has prevalence estimates in the range of 0.1–0.2% of the general population, and are higher in the Middle East and other countries where sesame seeds are used in traditional foods. Reporting of sesame seed allergy has increased in the 21st century, either due to a true increase from exposure to more sesame foods or due to an increase in awareness. Increasing sesame allergy rates have induced more countries to regulate food labels to identify sesame ingredients in products and the potential for allergy. In the United States, sesame became the ninth food allergen with mandatory labeling, effective 1 January 2023.
This release of pre-formed mediators enables not only rapid anaphylactic reactions and allergic responses but also initiates recruitment of leukocytes to sites of pathogen invasion, activation of innate immune processes, and inflammatory responses (1). ... Two types of degranulation have been described for MC: piecemeal degranulation (PMD) and anaphylactic degranulation (AND) (Figures 1 and 2). Both PMD and AND occur in vivo, ex vivo, and in vitro in MC in human (78–82), mouse (83), and rat (84). PMD is selective release of portions of the granule contents, without granule-to-granule and/or granule-to-plasma membrane fusions. ... In contrast to PMD, AND is the explosive release of granule contents or entire granules to the outside of cells after granule-to-granule and/or granule-to-plasma membrane fusions (Figures 1 and 2). Ultrastructural studies show that AND starts with granule swelling and matrix alteration after appropriate stimulation (e.g., FcεRI-crosslinking).