Allergy: Type I Hypersensitivity Reaction
Type I hypersensitivity reaction is an unusual immune response triggered by exposure to specific antigens known as allergens. Type I hypersensitivity reactions are mediated by IgE antibodies and comprise many of the most common allergies to respiratory allergens, like pollen and dust mites. Almost half of the U.S. population that is 54.3% suffers from type I hypersensitivity reactions. It encloses the most common allergic reactions along with hay fever, asthma, atopic dermatitis, and food allergies. The incidence of allergy continues to boost in the human population, and understanding the immune mechanisms behind the response has already led to new therapies. Below we define the molecular and cellular participants in the different type I hypersensitivities, as well as the principle behind the current treatments.
Also check out- Types of ELISA – My Biology Dictionary
Table of Contents
Immunoglobulin-E Antibodies Are Responsible for Type I Hypersensitivity:
To begin with, type I hypersensitivity reactions (allergies) are initiated by the interaction or synergy between an IgE antibody and a multivalent antigen. Classic Experiment describes the brilliant series of experiments by K. Ishizaka and T. Ishizaka in the 1960s and 1970s that led to the recognition of IgE as the class of antibody responsible for allergies.
Common allergens associated with Type I Hypersensitivity Reaction:
Plant pollens Foods Drugs Insect products
Rye grass Nuts Penicillin Bee venom
Ragweed Seafood Sulfonamides Wasp venom
Timothy grass Eggs Local anesthetics Ant venom
Birch trees Peas, BeansMilk Salicylate Cockroach calyx
Mold spores, Animal hair, dander, Latex, Foreign serum Vaccines, etc.
In normal human beings, the level of IgE in serum is the minimum of any of the immunoglobulin classes. This makes more physiochemical studies of this molecule particularly challenging. It was not until the discovery of IgE-producing myeloma by Johansson and Bennich in 1967, that major analyses of IgE could be undertaken.
Many Allergens Can Elicit a Type I Response:
Healthy individuals generate IgE antibodies only in response to parasitic infections. Yet, some people referred to as atopic, are predisposed to develop IgE antibodies against common environmental antigens, such as those listed in the above table. The chemical study revealed that most, if not all, allergens are either protein or glycoprotein in nature, with multiple antigenic sites or epitopes for each molecule. For several years, scientists tried unsuccessfully to find any structural commonalities among molecules that induced distress in affected individuals. But in recent times several features shared by many allergens have begun to provide clues to the biological basis of their activity.
First, many allergens have an innate or intrinsic enzymatic activity that affects the immune response. For example, allergen extracts from dust mites and cockroaches. As well as from fungi and bacteria are nearly high in protease activity.
Second, many allergens consist of potentially Pathogen- Associated Molecular Patterns, or PAMPS. It is capable of interacting with receptors of the innate immune system. Also initiating a cascade of responses leads to an allergic response. Anyhow, it is unclear why this cascade is stimulated in only a sub-division of individuals.
Third, many allergens enter or come inside the host through mucosal tissues at very low concentrations. It tends to dispose the individual to generate TH2 responses, leading to B-cell secretion of IgE.
Type I Hypersensitivities Are Characterized by Both Early and Late Responses:
Type I hypersensitivity responses or feedback are divided into an immediate early response and one or more late-phase responses. The early or initial response occurs within minutes of allergen exposure. As a results from the release of histamine, leukotrienes, and prostaglandins from local mast cells.
Anyhow, hours after the immediate phase of a type I hypersensitivity reaction initiates to diminish. Mediators released during the course of the reaction induce localized inflammation called the Late phase reaction. Cytokines released from mast cells, especially TNF-alpha and IL-1, raise the expression of cell adhesion molecules on venular endothelial cells. Thus, facilitating the influx of neutrophils, eosinophils, and TH2 cells that characterizes this phase of the response.
Image source:Muñoz-Cano, R. M., Casas-Saucedo, R., Valero Santiago, A., Bobolea, I., Ribó, P., & Mullol, J. (2019). Platelet-activating factor (PAF) in allergic rhinitis: clinical and therapeutic implications. Journal of clinical medicine, 8(9), 1338.
Eosinophils play a main role in the late-phase reaction. Eosinophil chemotactic factor, released by mast cells during the initial reaction, attracts huge numbers of eosinophils to the affected site. Cytokines released at the site, including IL-3, IL-5, and GM-CSF. It contributes to the growth and differentiation of these cells, which are then activated by the binding of antibody-coated antigens. This leads to degranulation and more release of inflammatory mediators that contribute to the huge tissue damage typical of the late-phase reaction. Neutrophils are another leading participant in late-phase reactions. These are attracted to the site of an ongoing type I reaction by a neutrophil chemotactic factor released from degranulating mast cells. Once activated, the neutrophils release their granule contents along with lytic enzymes, platelet-activating factors, and leukotrienes.
Few Categories of Type I Hypersensitivity Reactions:
The clinical demonstrations of type I reactions can range from life-threatening conditions. Such as systemic anaphylaxis and severe asthma, to localized reactions, like hay fever and eczema.
Systemic Anaphylaxis:
It is a shocklike and usually fatal state that occurs within minutes of exposure to an allergen. It is usually initiated by an allergen introduced straight into the bloodstream or absorbed from the gut or skin. Asphyxiation can lead to death within 2-4 minutes of exposure to the allergen.
Also check out-Mechanism of Immune Response – My Biology Dictionary
Localized Hypersensitivity Reactions:
In this, the pathology is finite to a specific target tissue or organ and usually occurs at the epithelial surfaces first exposed to allergens. Atopic allergies include a large range of IgE-mediated disorders, like allergic rhinitis (hay fever), asthma, atopic dermatitis (eczema), and food allergies.
Food Allergies:
Food allergies are another familiar type of atopy. In children, food allergies account for more anaphylactic responses than any alternative type of allergy. They are maximum in frequency among infants and toddlers (6%–8%) and decrease slightly with maturity. The most common or familiar food allergens for children are found in cow’s milk, eggs, peanuts, tree nuts, soy, wheat, fish, and shellfish. Among adults, nuts, fish, and shellfish are the dominant culprits.
Diagnostic Tests and Treatments of Type I Hypersensitivity Reactions:
Hyposensitization:
For several years, physicians have been treating allergic patients with repeated exposure (through ingestion or injection) to increasing doses of allergens, in a procedure termed hyposensitization or immunotherapy. This method of treatment attacks the disease mechanism of the allergic individual at the source and, when it works, is by far the most effective way to manage allergies. Hyposensitization can decrease or even eliminate symptoms for months or years after the desensitization course is complete.
Antihistamines, Leukotriene Antagonists, and Inhalation Corticosteroids:
- Antihistamines have been the most advantageous drugs for the treatment of allergic rhinitis. These drugs inhibit or forbid histamine activity by binding and blocking histamine receptors on target cells.
- Inhalation therapy with low-dose corticosteroids lower inflammation by inhibiting innate immune cell activity. It has been used successfully to weaken the frequency and severity of asthma attacks.
- Leukotriene antagonists, specially montelukast, have also been used to treat type I hypersensitivities and are equal in effectiveness to antihistamines.
Immunotherapeutics:
Therapeutic anti-IgE antibodies have been developed; one such antibody, omalizumab and is available as a pharmacological agent. Omalizumab binds the Fc region of IgE and inhibits IgE-FcR interactions. It is used to treat both allergic rhinitis and allergic asthma. Yet, for the treatment of allergic rhinitis, omalizumab is no more effective than second-generation antihistamines. It is hardly prescribed because of its higher cost.
To sum it up, Type I hypersensitivity is also known as an immediate reaction and comprises immunoglobulin E (IgE) mediated release of antibodies against the soluble antigen. This results in mast cell degranulation and the release of histamine and other inflammatory mediators. Thus, symptoms are – a feeling of warmth, flushing, a red, itchy rash, feelings of light-headedness, restlessness of breath, throat tightness, anxiety, pain/cramps or vomiting, and diarrhoea.
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Team MBD
Further reading- Type I Hypersensitivity Reaction – StatPearls – NCBI Bookshelf (nih.gov)
