Tiêu đề 9. Hypersensitivty.docx.pdf ✅

Immunology Serology Lecture Discussion Notes Hypersensitivity Overview In previous chapters, we discussed how the immune system functions as a defense mechanism, protecting the body from harmful antigens. However, there are instances when the immune response itself becomes harmful. This occurs when the body overreacts to a normally harmless antigen, leading to tissue damage, disease, or even death. This exaggerated immune response is known as or termed as hypersensitivity. British immunologists P. G. H. Gell and R. R. A. Coombs classified hypersensitivity reactions into four distinct types, each differing in their immune mechanisms and effects on the body. These four types are as follows: 1. Type I Hypersensitivity (Anaphylactic Hypersensitivity) o Mediated by IgE antibodies. o Mast cells and basophils release histamine and other inflammatory mediators when exposed to an allergen. o Leads to rapid allergic reactions such as anaphylaxis, asthma, and allergic rhinitis. 2. Type II Hypersensitivity (Antibody-Mediated Cytotoxic Hypersensitivity) o Mediated by IgG or IgM antibodies. o Antibodies target host cell surface antigens, leading to cell destruction or dysfunction. o Examples include hemolytic disease of the newborn (HDN), transfusion reactions, and certain autoimmune disorders. 3. Type III Hypersensitivity (Immune Complex-Mediated Hypersensitivity) o Involves IgG or IgM antibodies forming immune complexes with soluble antigens. o These complexes deposit in tissues, triggering complement activation and neutrophil recruitment, leading to inflammation and tissue damage. o Examples include systemic lupus erythematosus (SLE) and rheumatoid arthritis. 4. Type IV Hypersensitivity (Delayed-Type Hypersensitivity, or Cell-Mediated Hypersensitivity) o Unlike the previous types, this reaction is T-cell mediated rather than antibody-mediated. o Sensitized T cells release cytokines, leading to inflammation and tissue destruction. o The response is delayed (24-48 hours after exposure) and is seen in contact dermatitis, tuberculin skin tests (e.g., Mantoux test), and transplant rejection. Classification: Immediate vs. Delayed Hypersensitivity ● Types I, II, and III are classified as immediate hypersensitivity reactions because symptoms appear within minutes to a few hours after antigen exposure. ● Type IV is referred to as delayed hypersensitivity, as symptoms manifest 24 to 48 hours after antigen contact. Type I Hypersensitivity (Immediate Hypersensitivity) Mechanism of Type I Hypersensitivity Type I hypersensitivity is an allergic reaction that occurs rapidly after exposure to an allergen. It involves the immune system overreacting to harmless environmental substances. The key steps in this reaction are: 1. Sensitization Phase: o Upon first exposure to an allergen, antigen-presenting cells (APCs) process and present the allergen to naïve CD4+ T cells.
Immunology Serology Lecture Discussion Notes o These cells differentiate into Th2 cells, which release cytokines (IL-4, IL-5, IL-13). o IL-4 promotes B-cell class switching to produce IgE antibodies specific to the allergen. o IgE binds to FcεRI receptors on mast cells and basophils, sensitizing them to future exposures. 2. Activation Phase (Subsequent Exposures): o When the same allergen re-enters the body, it cross-links IgE on mast cells and basophils. o This triggers degranulation, releasing inflammatory mediators like histamine, prostaglandins, and leukotrienes, which cause allergic symptoms. 3. Effector Phase: o Histamine causes vasodilation, increased vascular permeability, and smooth muscle contraction (leading to symptoms like swelling, mucus secretion, and bronchoconstriction). o Leukotrienes and prostaglandins contribute to prolonged inflammation, further exacerbating symptoms. Clinical Manifestations of Type I Hypersensitivity The severity of symptoms varies based on the site of allergen exposure and individual sensitivity. ● Localized Reactions: o Allergic rhinitis (hay fever): Sneezing, nasal congestion, watery eyes. o Asthma: Airway inflammation, bronchoconstriction, wheezing. o Hives (urticaria): Red, itchy welts on the skin. o Food allergies: Nausea, vomiting, diarrhea, abdominal pain, hives. ● Systemic Anaphylaxis (Severe Reaction): o Symptoms: Widespread vasodilation, bronchoconstriction, severe hypotension, loss of consciousness. o Triggers: Common causes include peanut allergies, insect stings, shellfish, and certain medications (e.g., penicillin). o Medical Emergency: Requires immediate administration of epinephrine to counteract life-threatening symptoms. Diagnostic Methods for Type I Hypersensitivity Allergy testing is used to identify specific allergens that trigger hypersensitivity reactions. 1. In Vivo Skin Tests (Direct Skin Testing) ● Percutaneous (Prick/Puncture) Test: o Small drops of allergen extract are introduced into the upper layers of the skin. o A wheal-and-flare reaction (redness and swelling) within 15–20 minutes indicates sensitivity. ● Intradermal Test: o Injects diluted allergen under the skin for greater sensitivity. o Used when prick tests are negative but allergy is still suspected. o Higher risk of anaphylactic reaction compared to the percutaneous test. 2. Allergen-Specific IgE Testing (Serological Testing) ● Fluoroimmunoassays (e.g., ImmunoCAP): Detects allergen-specific IgE in blood samples. ● Radioallergosorbent Test (RAST): An older test using radiolabeled anti-IgE. ● Microarray Technology: Can detect over 100 allergens using a single blood sample. ● Point-of-care Lateral Flow Assay: A rapid finger-prick test for common allergens.
Immunology Serology Lecture Discussion Notes 3. Total Serum IgE Testing ● Measures overall IgE levels, useful for assessing atopic diseases (asthma, eczema). Treatment of Type I Hypersensitivity Treatment strategies aim to prevent allergen exposure, relieve symptoms, and modulate immune responses. 1. Allergen Avoidance ● Using allergen-proof covers for mattresses and pillows. ● Avoiding known food allergens, pets, or environmental triggers. 2. Pharmacological Therapy ● Antihistamines: Block histamine receptors to reduce itching, swelling, and mucus production. ● Decongestants: Reduce nasal swelling (e.g., pseudoephedrine). ● Bronchodilators: Relax airway muscles in asthma. ● Leukotriene Receptor Antagonists (e.g., Montelukast): Reduce inflammation in asthma. ● Mast Cell Stabilizers (e.g., Cromolyn Sodium): Prevent degranulation. ● Corticosteroids: Suppress inflammation in severe allergic reactions. ● Epinephrine (Adrenaline): First-line treatment for anaphylaxis; acts as a vasoconstrictor and bronchodilator. 3. Immunotherapy (Allergy Desensitization) ● Allergy Immunotherapy (AIT): o Gradual exposure to increasing allergen doses to induce immune tolerance. o Shifts immune response from Th2 (IgE-mediated) to Th1 (IgG4-mediated), reducing allergic reactions. ● Routes of Administration: o Subcutaneous (SCIT): Injections over 3–5 years, risk of anaphylaxis. o Sublingual (SLIT): Allergen extract under the tongue, safer for food allergies. ● Recombinant Allergens & Allergoids: o Chemically modified allergens to reduce IgE binding, improving safety. 4. Anti-IgE Therapy (Omalizumab) ● Omalizumab (Xolair): o A monoclonal antibody that binds free IgE, preventing it from sensitizing mast cells. o Downregulates FcεRI receptor expression, reducing allergic responses. o Used in moderate to severe asthma and being tested for other allergies. Summary Type I hypersensitivity is an IgE-mediated immune response that leads to allergic reactions ranging from mild (rhinitis, asthma, hives) to life-threatening (anaphylaxis). Diagnosis involves skin tests and IgE immunoassays, while treatment includes avoidance strategies, medication, immunotherapy, and anti-IgE therapy. Emerging approaches like recombinant allergens and microarray testing are improving diagnostic accuracy and treatment outcomes. Type II Hypersensitivity (Antibody-Mediated Cytotoxicity) ● Mediated by IgG & IgM antibodies that target cell surface antigens (self or foreign). ● Can result in cell destruction, inhibition, or overstimulation.
Immunology Serology Lecture Discussion Notes Mechanisms of Cell Damage: 1. Complement Activation → Formation of Membrane Attack Complex (MAC) → Cell lysis. 2. Opsonization & Phagocytosis → Antibody or C3b-coated cells are engulfed by macrophages or neutrophils. 3. Antibody-Dependent Cellular Cytotoxicity (ADCC) → Natural Killer (NK) cells & macrophages release cytotoxic enzymes. Effects of Type II Hypersensitivity: 1. Cell Destruction (Cytotoxic Reactions) o Blood transfusion reactions (ABO incompatibility) o Hemolytic disease of the newborn (HDN) (Rh incompatibility) o Autoimmune hemolytic anemia (antibodies against own RBCs) 2. Cell Function Inhibition o Myasthenia Gravis → Autoantibodies block acetylcholine (ACH) receptors, leading to muscle weakness. 3. Cell Overstimulation o Graves' Disease → Autoantibodies stimulate TSH receptors, causing hyperthyroidism. Clinical Examples: 1. Transfusion Reactions o Occur when a patient receives incompatible blood. o Acute reactions involve IgM-mediated complement activation, leading to hemolysis, DIC, shock, and renal failure. o Delayed reactions occur 1–2 weeks post-transfusion, usually IgG-mediated, leading to mild hemolysis and jaundice. 2. Hemolytic Disease of the Newborn (HDN) o Rh-negative mother produces anti-D IgG antibodies after exposure to Rh-positive fetal blood. o In subsequent pregnancies, IgG crosses placenta, destroying fetal RBCs → Erythroblastosis fetalis, jaundice, kernicterus. o Prevention: Rh-negative mothers receive Rhogam (anti-D IgG) at 28 weeks & after delivery. 3. Autoimmune Hemolytic Anemia (AIHA) o Antibodies target self RBCs, leading to anemia, jaundice, fever, pallor. o Types: ▪ Warm AIHA (IgG-mediated, reacts at 37°C, extravascular hemolysis) ▪ Cold AIHA (reacts below 30°C, intravascular hemolysis) o Treatment: Corticosteroids, splenectomy, anti-CD20 (rituximab). 4. Drug-Induced Hemolytic Anemia o Drugs act as haptens (penicillin, cephalosporins) or form immune complexes (quinidine), leading to RBC destruction. Summary Type II hypersensitivity primarily involves antibody-mediated cell damage through complement activation, phagocytosis, or abnormal cell signaling, leading to a range of autoimmune and transfusion-related disorders.