Allergy is an overactive immune (hypersensitivity) reaction to a harmless entity sensed as dangerous by the immune system. Type 1 hypersensitivity involves the production of Ig-E antibodies against an allergen. Different types of allergies have been described and include food allergies, drug allergies, allergies to plant components (pollen) and allergies to animal products. Manifestations of allergic reactions include redness of the skin (contact allergy), sneezing, wheezing and edema and can ultimately lead to anaphylactic shock. Different populations of immune cells are engaged in an allergic reaction, including antigen presenting cells (e.g., dendritic cells), mast cells and Ig-E producing B cells and T cells.
What causes allergy?
Most allergies are caused by a known allergen but cases of allergies of unknown origin exist. Allergens can be airborne (e.g., pollen, dust) or can come from the food ingested (e.g., peanut, eggs, shellfish), medications consumed or substances that come into contact with the skin (e.g., latex, insect bite).
Different Types of Hypersensitivity
Type I hypersensitivity: anaphylactic response
Type I hypersensitivity reaction, also known as anaphylactic response, is characterized by a rapid Ig-E antibody production. These Ig-E bind to mast cells and basophils and induce the release of histamine-containing granules. Some examples of type I hypersensitivity reactions include food allergy, allergic rhinitis, allergic bronchial asthma, atopic eczema, drug allergy and anaphylactic shock.1
In type 1 asthma, the Ig-E bind to mast cells, resulting in the release of histamines and leukotrienes leading to inflammation of eosinophils, which is a hallmark of allergic inflammatory response and a degranulation process. This is also accompanied by the release of inflammatory cytokines such as IL-4 and IL-5.2
Type II hypersensitivity: cytotoxic
Type II hypersensitivity is characterized by Ig-M and Ig-G antibodies that bind to cell surface antigens inducing activation of complement cascades and phagocytosis.1 Type II hypersensitivity reactions are common in some types of autoimmune diseases, such as autoimmune neutropenia of rheumatoid disorders.
Type III hypersensitivity: immune complex reaction
Type III hypersensitivity reaction is also known as immune-complex reaction. It also involves Ig-M and Ig-G antibodies, but they react with soluble antigens. The complement system is also activated, and chemo-attracted neutrophils cause local inflammation and tissue damage. This type of hypersensitivity is observed in serum sickness arthritis and glomerulonephritis. Other types of antibodies such as Ig-A have also been described in type III hypersensitivity. In Berger’s disease, also known as immunoglobulin A nephropathy, damage of the kidney is linked to Ig-A deposits and local inflammation.3
Type IV hypersensitivity: delayed reaction
A fourth type of hypersensitivity is classified as delayed hypersensitivity reaction (DHR) and is characterized by infiltration of antigen-specific T cells. Different subtypes of type IV hypersensitivity are described based on the infiltrating T cells: type IV-a, -b, -c, -d associated with Th1, Th2, T-effector and GM-CSF producing T cells, respectively.4
References
- Justiz Vaillant AA, Vashisht R, Zito PM. Immediate hypersensitivity reactions. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 16, 2020.
- Peebles RS, Jr, Aronica MA. Proinflammatory pathways in the pathogenesis of asthma. Clin Chest Med. 2019;40(1):29-50. doi:10.1016/j.ccm.2018.10.014
- Stanley JC, Deng H. Progress in pathogenesis of immunoglobin A nephropathy. Cureus. 2020;12(6):e8789. doi:10.7759/cureus.8789
- Meng X, Yerly D, Naisbitt DJ. Mechanisms leading to T-cell activation in drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2018;18(4):317-324. doi:10.1097/ACI.0000000000000458
