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Hypersensitivity Reactions (Types I–IV)

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Adaptive Immunity and Lymphocyte DiversityAntibody Structure and Biological Functions+4 more→→Autoimmunity and Autoimmune DiseaseImmunopathology of Infectious Diseases: Protective vs. Pathogenic Immunity
pathology hypersensitivity adverse-reactions

Core Idea

Hypersensitivity reactions are excessive or inappropriate immune responses causing tissue damage. Type I (immediate, IgE-mediated, mast cells/basophils) manifests as allergies and anaphylaxis within minutes. Type II (cytotoxic, antibody-mediated) targets cell-surface antigens. Type III (immune complex) deposits complexes in tissues. Type IV (delayed, T cell-mediated) occurs without antibodies.

Explainer

From your study of adaptive immunity, you know that antibodies and T cells are powerful weapons against pathogens. But what happens when these same weapons are aimed at harmless substances, or when the immune response is disproportionate to the threat? Hypersensitivity reactions are immune responses that cause tissue damage to the host — the immune system working correctly in mechanism but incorrectly in target or magnitude. The Gell and Coombs classification divides these into four types based on the immune effector involved and the timing of the response.

Type I (immediate) hypersensitivity is what most people call "allergies." On first exposure to an allergen (pollen, peanut protein, bee venom), B cells produce IgE antibodies that bind to high-affinity FcεRI receptors on mast cells and basophils, priming them. On re-exposure, the allergen crosslinks adjacent IgE molecules on the mast cell surface, triggering rapid degranulation — the explosive release of preformed mediators like histamine, along with newly synthesized leukotrienes and prostaglandins. These mediators cause vasodilation, increased vascular permeability, smooth muscle contraction, and mucus secretion — the sneezing, swelling, and itching of allergic rhinitis, or in severe cases, the life-threatening systemic vasodilation and bronchospasm of anaphylaxis. The "immediate" label reflects the speed: symptoms appear within minutes because the mediators are preformed and ready to release.

Type II (cytotoxic) hypersensitivity involves IgG or IgM antibodies directed against antigens on the surface of the host's own cells. The antibody binds the cell surface and triggers destruction through complement activation, opsonization and phagocytosis, or antibody-dependent cellular cytotoxicity (ADCC). Classic examples include hemolytic disease of the newborn (maternal anti-Rh antibodies attacking fetal red blood cells), transfusion reactions from ABO blood group mismatch, and autoimmune hemolytic anemia. Type III (immune complex) hypersensitivity occurs when antigen-antibody complexes form in the blood and deposit in tissues — particularly blood vessel walls, kidney glomeruli, and joint spaces. These deposited complexes activate complement locally, recruiting neutrophils that release enzymes and reactive oxygen species, causing vasculitis, glomerulonephritis, or arthritis. Serum sickness and systemic lupus erythematosus involve Type III mechanisms.

Type IV (delayed-type) hypersensitivity is fundamentally different: it involves T cells rather than antibodies, and symptoms take 24–72 hours to develop because they require T cell activation, proliferation, and migration to the site. The tuberculin skin test (PPD test) is the classic example: injected mycobacterial antigens are recognized by memory T cells from prior exposure, which recruit macrophages and cause localized induration and swelling over 48–72 hours. Contact dermatitis (poison ivy, nickel allergy) is another Type IV response, where small chemical haptens modify skin proteins, creating neoantigens that activate T cells. Understanding which type of hypersensitivity underlies a clinical condition determines the treatment strategy — antihistamines for Type I, plasmapheresis or immunosuppression for Types II and III, and corticosteroids or T cell-targeted therapy for Type IV.

Practice Questions 5 questions

Prerequisite Chain

Understanding Zero → The Number Zero → Counting to Five → Counting to 10 → Counting to 20 → Counting a Set of Objects Up to 20 → Cardinality: The Last Number Counted → Matching Numerals to Quantities → Subitizing Small Quantities → Addition Within 10 → Number Bonds to 10 → Addition Within 20 → Doubles and Near Doubles → Doubles Facts Within 10 → Near Doubles Facts Within 20 → Mental Math Strategies for Addition → Mental Math: Adding and Subtracting Tens → Addition Within 100 → Repeated Addition as Multiplication → Multiplication as Equal Groups → Multiplication: Arrays → Basic Multiplication Facts (0s, 1s, 2s, 5s, 10s) → Multiplication Facts Within 100 → Division as Equal Sharing → Division as Grouping (Measurement Division) → Division: Grouping (Repeated Subtraction) Model → Division: Fair Sharing Model → Division as Equal Sharing → Division as Grouping → Basic Division Facts → Division Facts Within 100 → Multiplication and Division Fact Families → Relationship Between Multiplication and Division → Division Facts as Inverse of Multiplication → Remainders and Quotients in Division → Division Word Problems → Multi-Step Word Problems → Solving Multi-Step Word Problems → Multiplication Word Problems → Division Word Problems → Introduction to Long Division → Factors and Multiples → Prime and Composite Numbers → Equivalent Fractions → Relating Fractions and Decimals → Decimal Place Value → Integers and the Number Line → Comparing and Ordering Integers → Absolute Value → Adding Integers → Subtracting Integers → Multiplying Integers → Dividing Integers → Unit Rates → Proportions → Percent Concept → Converting Between Fractions, Decimals, and Percents → Operations with Rational Numbers → Two-Step Equations → Solving Multi-Step Equations → Equations with Variables on Both Sides → Angle Pairs: Complementary, Supplementary, and Vertical → Parallel Lines and Transversals → Corresponding Angles → Alternate Interior Angles → Triangle Angle Sum Theorem → Exterior Angle Theorem → Triangle Inequality Theorem → Similar Triangles: AA Similarity → Similar Triangles: SSS and SAS Similarity → Proportions in Similar Triangles → Right Triangle Trigonometry Introduction → Sine, Cosine, and Tangent Ratios → Trigonometric Ratios Review → Radian Measure → Converting Between Degrees and Radians → The Unit Circle → Graphing Sine and Cosine → Graphing Tangent and Reciprocal Trigonometric Functions → Derivatives of Trigonometric Functions → Antiderivatives → Indefinite Integrals → Basic Integration Rules → Riemann Sums → Definite Integral Definition → Double Integrals: Definition and Setup → Iterated Integrals and Fubini's Theorem → Double Integrals over Rectangular Regions → Double Integrals over General Regions → Applications of Double Integrals: Area, Mass, and Moments → Triple Integrals in Cartesian Coordinates → Triple Integrals in Cylindrical and Spherical Coordinates → Change of Variables and the Jacobian Determinant → Applications of Triple Integrals: Volume and Mass → Vector Fields and Their Representations → Line Integrals of Vector Fields → Work and Circulation → Line Integrals of Scalar and Vector Functions → Fundamental Theorem for Line Integrals → Conservative Vector Fields → Conservative Vector Fields and Potential Functions → Curl and Divergence of Vector Fields → Curl and Divergence → Divergence Theorem → Electric Flux and Divergence Theorem → Gauss's Law: Integral Form and Meaning → Solving Problems with Gauss's Law → Conductors in Electrostatic Equilibrium → Capacitance and Capacitors → Dielectrics → Dielectric Constant and Relative Permittivity → Electric Field Inside Dielectric Materials → Dielectric Materials and Polarization → Dielectric Susceptibility and Permittivity → Energy Density in Electric Fields → Electric Current and Current Density → Electrical Resistance and Resistivity → Ohm's Law and Circuit Elements → Electromotive Force (EMF) and Batteries → Kirchhoff's Circuit Laws: Voltage and Current → DC Circuit Network Analysis Methods → Transient Response in RC Circuits → RC Circuits → LC and RLC Circuits → AC Circuits: Fundamentals → Impedance and Reactance → AC Power and Resonance → Electromagnetic Waves → Postulates of Special Relativity → Time Dilation → Length Contraction → Lorentz Transformation → Relativistic Velocity Addition → Relativistic Momentum and Energy → Mass-Energy Equivalence and E=mc² → Photons as Particles with Energy and Momentum → Planck-Einstein Relation: Energy and Frequency → Photoelectric Effect → The Photon: Light as Quanta → Compton Scattering → Wave-Particle Duality → de Broglie Wavelength → The Schrödinger Equation → State Vectors and Wavefunctions → Quantum Superposition → Quantum Entanglement → Bell Theorem and Bell Inequalities → Postulates of Quantum Mechanics → Observables and Quantum Operators → Commutators and Commutation Relations → Quantum Angular Momentum → Quantum Mechanical Treatment of Hydrogen → Solving the Schrödinger Equation for Hydrogen Atom → Quantum Numbers → Electron Configuration → Periodic Trends → Covalent Bonding → Electronegativity and Bond Polarity → Ionic Bonding → Lewis Structures → VSEPR Theory and Molecular Geometry → Molecular Geometry and Electron Pair Geometry → Molecular Polarity and Dipole Moments → Intermolecular Forces → States of Matter and Phase Changes: Melting, Boiling, and Sublimation → Gas Laws and the Ideal Gas Equation → Gas Stoichiometry and Volume-Volume Calculations → Thermochemistry and Enthalpy → Heat Capacity and Calorimetry → Entropy and Molecular Disorder → Spontaneity and ΔG → Entropy and Gibbs Free Energy → Chemical Equilibrium → Acid-Base Chemistry → Weak Acid Ionization → Weak Base Ionization → Acid and Base Strength: Ka, Kb, and Ionization → Leaving Groups and Nucleofugality → SN2 Substitution Reactions → SN1 Substitution Reactions → E1 Elimination Reactions → Alcohols and Ethers: Structure, Properties, and Nomenclature → Reactions of Alcohols → Aldehydes and Ketones: Structure and Reactivity → Oxidation Reactions in Organic Chemistry → Oxidation of Alcohols to Aldehydes and Ketones → Aldehyde and Ketone Structure and Nomenclature → Nucleophilic Addition to Aldehydes and Ketones → Carboxylic Acids and Their Derivatives → IUPAC Nomenclature of Carbonyls and Carboxylic Acids → IUPAC Nomenclature of Alkenes → Electrophilic Addition to Alkenes → Aromaticity and Benzene → Electrophilic Aromatic Substitution (EAS) → Nucleophilic Aromatic Substitution (SNAr) → Nucleophilic Acyl Substitution → Amines: Structure, Basicity, and Reactions → Amine Reactivity: Nucleophilicity and Basicity → Amino Acid Structure and Properties → Peptide Bonds and Polypeptide Formation → Protein Primary Structure → Protein Secondary Structure → Protein Tertiary Structure → Ion Channels and Selective Permeability Mechanisms → Osmotic Regulation and Cellular Water Balance → Osmosis and Tonicity → Active Transport → Cell Signaling and Signal Transduction → Homeostasis and Feedback Loops → Cardiovascular System Overview → Blood Composition and Function → Innate Immune Response → Inflammation and Wound Healing → Foundations of Immunology → Innate Immune System Components → Adaptive Immunity and Lymphocyte Diversity → Major Histocompatibility Complex Structure and Function → Antigen Processing and Presentation Pathways → Dendritic Cells and Professional Antigen-Presenting Cells → MHC Class II Antigen Presentation Pathway → CD4+ Helper T Cell Differentiation and Function → B Cell Activation and Germinal Center Responses → Class Switch Recombination and Isotype Switching → Antibody Isotypes and Effector Functions → Type II Hypersensitivity: Antibody-Mediated Cytotoxic Reactions → Type I Hypersensitivity: Allergic Reactions and IgE → High-Affinity IgE Receptor and Mast Cell Activation → Mast Cells and Basophils in Allergic and Innate Responses → Hypersensitivity Reactions (Types I–IV)

Longest path: 229 steps · 1222 total prerequisite topics

Prerequisites (6)

Leads To (2)