Immunologic Mechanisms of Hypersensitivity Reactions

Chapter 8 This chapter outlines the different types of immune system alterations, specifically hypersensitivity reactions and deficiencies in immunity. Hypersensitivity reactions can be categorized by the immunologic mechanism causing the disease and the source of the antigen being attacked by the immune system. There are four main types of hypersensitivity reactions: type I (IgE-mediated reactions), type II (tissue-specific reactions), type III (immune complex-mediated reactions), and type IV (cell-mediated reactions). Hypersensitivity reactions Hypersensitivity reactions are altered immunologic responses to antigens that result in disease or damage They can be classified by the immunologic mechanism (types I, II, III, and IV) and by the source of the antigen (allergy, autoimmunity, and alloimmunity) The mechanism that initiates hypersensitivity reactions is not completely understood, but genetic, infectious, and environmental factors are contributing factors Immunologic mechanisms of hypersensitivity reactions Type I: IgE-mediated reactions, involving mast cells and IgE antibodies Type II: Tissue-specific reactions, involving IgG and IgM antibodies, as well as NK cells, macrophages, and neutrophils Type III: Immune complex-mediated reactions, involving IgG and IgM antibodies and neutrophils Type IV: Cell-mediated reactions, involving lymphocytes and macrophages Development of hypersensitivity reactions Hypersensitivity reactions require sensitization to a specific antigen, resulting in a primary immune response Memory B cells and T cells are formed during the primary immune response Disease symptoms appear upon secondary exposure to the antigen, activating memory cells Hypersensitivity reactions can be immediate or delayed Hypersensitivity reactions: Immediate hypersensitivity reactions occur within minutes to a few hours after exposure to an antigen Delayed hypersensitivity reactions may take several hours to appear and are at maximal severity days after reexposure to the antigen Immediate reactions are caused by antibody, while delayed reactions are caused by cells Anaphylaxis: Anaphylaxis is the most rapid and severe immediate hypersensitivity reaction It occurs within minutes of reexposure to the antigen Can be systemic or cutaneous Symptoms of systemic anaphylaxis include pruritus, erythema, vomiting, abdominal cramps, diarrhea, and breathing difficulties Severe reactions may include contraction of bronchial smooth muscle, edema of the throat, and decreased blood pressure that can lead to shock and death Examples of systemic anaphylaxis are allergic reactions to bee stings, peanuts, shellfish, or eggs Cutaneous anaphylaxis results in local symptoms related to inflammation, such as pain, swelling, and redness at the site of exposure to an antigen Mechanism of Type I hypersensitivity reactions: Type I reactions are mediated by antigen-specific immunoglobulin E (IgE) and tissue mast cells First exposure to an allergen leads to antigen processing and presentation to B lymphocytes by an antigen-presenting cell (APC) Th2 cells produce specific cytokines that favor maturation of B lymphocytes into plasma cells that secrete IgE IgE binds to the surface of mast cells via IgE-specific Fc receptors, sensitizing the mast cell During reexposure to the allergen, the cross-linking of IgE on mast cells leads to degranulation and release of histamine Histamine induces local edema, smooth muscle contraction, mucous secretion, and other characteristics of acute inflammatory reactions IgE has a short life span in blood and rapidly binds to Fc receptors on mast cells Histamine is the most potent preformed mediator of IgE-mediated hypersensitivity Histamine and Allergic Reactions Histamine acts on histamine 1 (H1) receptors Causes bronchial constriction, edema, and vasodilation Interacts with H2 receptors to increase gastric acid secretion Manifestations of Type I Hypersensitivity Reactions Pruritus (itching) Conjunctivitis Rhinitis Angioedema (swelling) Laryngeal edema Urticaria (hives) Hypotension (low blood pressure) Bronchospasm (asthma) Dysrhythmias (irregular heartbeat) Gastrointestinal cramps and malabsorption Secondary Mediators and Late Phase Reaction Mast cells synthesize secondary mediators (leukotrienes, prostaglandins, platelet activating factor) Secondary mediators attract other immune cells and activate kinins and complement Responsible for late phase reaction that occurs 2 to 24 hours late Gastrointestinal Allergy Caused by allergens entering through the mouth (foods or medicines) Results in increased fluid secretion and peristalsis Symptoms include vomiting, diarrhea, and abdominal pain Common food allergens are milk, chocolate, citrus fruits, eggs, wheat, nuts, peanut butter, and fish Food Allergies Allergy to shellfish is the most common food allergy in adults Food allergies can result from unidentifiable products of food processing or interaction with drugs or additives Exposure to peanut butter in the first year of life creates tolerance to peanut allergens: Results in a 70% reduction in the risk for later peanut allergy Mother's consumption of peanuts while breastfeeding and introducing peanuts to the infant's diet further reduces the risk Peanut antigens delivered to the infant along with maternal immunoglobulins, immune cells, cytokines, and microbiota prime the infant immune system for tolerance Guidelines for introducing peanuts to infants: Infants aged 4 to 6 months should be given age-appropriate peanut-containing foods In high-risk children, peanuts should be administered after testing for peanut-specific IgE levels or performing skin-prick tests with peanut allergen If strong sensitivity is found, peanut exposure should occur under the supervision of a specialist Urticaria (hives) and its causes: Hives are localized release of histamine and increased vascular permeability Can be caused by immunologic reactions or nonimmunologic factors such as cold temperatures, stress, medications, systemic diseases, or malignancies