Immunobiology Unit 13 ReviewHypersensitivity Reactions and Allergies

Key Concepts and Definitions

• Hypersensitivity reactions occur when the immune system responds inappropriately or excessively to a specific antigen or allergen
• Allergies involve an overreaction of the immune system to typically harmless substances (pollen, food proteins, medications)
• Sensitization refers to the initial exposure to an allergen that primes the immune system for future reactions
• Anaphylaxis represents a severe, potentially life-threatening systemic allergic reaction involving multiple organ systems
  • Symptoms can include difficulty breathing, hives, swelling, and a rapid drop in blood pressure
• Atopy describes a genetic predisposition to develop allergic diseases (asthma, eczema, allergic rhinitis)
• Mast cells and basophils play a central role in allergic reactions by releasing inflammatory mediators (histamine, leukotrienes, cytokines)
• IgE antibodies bind to specific allergens and trigger the release of inflammatory mediators from mast cells and basophils

Types of Hypersensitivity Reactions

• Type I (Immediate) hypersensitivity involves IgE-mediated release of inflammatory mediators from mast cells and basophils
  • Examples include allergic rhinitis, asthma, and anaphylaxis
• Type II (Antibody-dependent) hypersensitivity occurs when antibodies bind to cell surface antigens, leading to cell destruction
  • Involves complement activation and phagocytosis
  • Examples include autoimmune hemolytic anemia and Graves' disease
• Type III (Immune complex-mediated) hypersensitivity results from the deposition of antigen-antibody complexes in tissues
  • Triggers complement activation and inflammation
  • Examples include serum sickness and systemic lupus erythematosus (SLE)
• Type IV (Delayed-type) hypersensitivity is mediated by T cells and occurs 24-72 hours after antigen exposure
  • Involves the release of cytokines and the recruitment of macrophages and other immune cells
  • Examples include contact dermatitis and tuberculosis skin test reactions

Immune Mechanisms Involved

• Allergic reactions begin with sensitization, where the immune system encounters an allergen and generates specific IgE antibodies
• Upon re-exposure to the allergen, IgE antibodies bound to mast cells and basophils cross-link, triggering degranulation and the release of inflammatory mediators
• T helper 2 (Th2) cells play a crucial role in the development of allergic responses by producing cytokines (IL-4, IL-5, IL-13) that promote IgE production and eosinophil activation
• Regulatory T cells (Tregs) help maintain immune tolerance and can suppress allergic responses
• Innate immune cells (dendritic cells, innate lymphoid cells) contribute to the initiation and amplification of allergic inflammation
• Eosinophils, recruited by IL-5, release granule proteins that cause tissue damage and inflammation in allergic diseases

Common Allergens and Triggers

• Inhalant allergens include pollen, dust mites, animal dander, and mold spores
  • Often associated with allergic rhinitis and asthma
• Food allergens commonly include peanuts, tree nuts, milk, eggs, soy, wheat, fish, and shellfish
  • Can cause symptoms ranging from mild (hives, itching) to severe (anaphylaxis)
• Insect venoms from bees, wasps, and fire ants can trigger severe allergic reactions
• Medications such as penicillin, sulfa drugs, and NSAIDs can cause hypersensitivity reactions
  • Reactions can range from mild (rash) to severe (anaphylaxis)
• Contact allergens include nickel, latex, and certain chemicals in cosmetics and personal care products
  • Often cause contact dermatitis, an itchy, red rash at the site of contact

Diagnosis and Testing Methods

• Skin prick tests involve introducing small amounts of allergens into the skin and observing for a local reaction (wheal and flare)
  • Positive results indicate sensitization to the allergen
• Intradermal tests involve injecting allergens into the dermis and are more sensitive than skin prick tests
• Specific IgE (sIgE) blood tests measure the levels of IgE antibodies specific to a particular allergen
  • Elevated sIgE levels suggest sensitization to the allergen
• Oral food challenges involve the supervised ingestion of a suspected food allergen to confirm or rule out a food allergy
• Patch tests are used to diagnose contact dermatitis by applying potential allergens to the skin for 48 hours and assessing for a delayed reaction
• Spirometry and peak flow measurements evaluate lung function in patients with asthma

Treatment Approaches

• Allergen avoidance remains the primary strategy for preventing allergic reactions
  • Includes environmental control measures (air filters, dust mite covers) and dietary modifications
• Antihistamines block the effects of histamine and provide symptomatic relief for allergic rhinitis, hives, and itching
• Corticosteroids, both topical and systemic, reduce inflammation and are used to treat various allergic conditions (asthma, eczema, allergic rhinitis)
• Bronchodilators (beta-2 agonists) relax airway smooth muscle and improve airflow in asthma
• Leukotriene modifiers block the action of leukotrienes and are used in the management of asthma and allergic rhinitis
• Allergen immunotherapy involves the administration of gradually increasing doses of allergens to induce tolerance
  • Can be administered subcutaneously (allergy shots) or sublingually (tablets or drops)
• Epinephrine is the first-line treatment for anaphylaxis and is administered intramuscularly to reverse severe symptoms

Prevention Strategies

• Early introduction of potentially allergenic foods (peanuts, eggs) may help prevent the development of food allergies in high-risk infants
• Exclusive breastfeeding for the first 4-6 months of life may reduce the risk of developing allergic diseases
• Probiotics and prebiotics may modulate the gut microbiome and influence the development of allergic diseases
• Vitamin D supplementation during pregnancy and early life may reduce the risk of allergic diseases, particularly asthma
• Smoking cessation and avoidance of secondhand smoke can reduce the risk and severity of asthma and other allergic diseases
• Regular cleaning and the use of air filters can help reduce exposure to indoor allergens (dust mites, pet dander)
• Wearing protective clothing and using insect repellents can help prevent insect sting allergies

Clinical Relevance and Case Studies

• Case 1: A 25-year-old woman presents with itchy, watery eyes, sneezing, and a runny nose during the spring months. She is diagnosed with allergic rhinitis due to tree pollen sensitization and treated with antihistamines and nasal corticosteroids.
• Case 2: A 4-year-old boy develops hives, swelling of the lips and tongue, and difficulty breathing after eating peanut butter. He is diagnosed with a peanut allergy and prescribed an epinephrine auto-injector for emergency use.
• Case 3: A 35-year-old man experiences a severe allergic reaction after being stung by a bee, with symptoms including hives, throat swelling, and low blood pressure. He is treated with intramuscular epinephrine and referred for venom immunotherapy.
• Case 4: A 50-year-old woman with a history of chronic asthma presents with worsening cough, wheezing, and shortness of breath. She is found to have poorly controlled asthma and is started on a combination of inhaled corticosteroids and long-acting beta-2 agonists.
• Case 5: A 2-year-old girl develops a scaly, itchy rash on her cheeks and extremities. She is diagnosed with atopic dermatitis and treated with topical corticosteroids and moisturizers, along with recommendations for gentle skin care and avoidance of irritants.