Snapshot A 12-year-old boy presents to the emergency department with dyspnea and urticaria. His symptoms began approximately 30 minutes after being stung by bee. Medical history is significant for asthma and an allergy to shellfish. On physical exam, breathing is labored, and wheezes are appreciated on pulmonary auscultation. Airway, breathing, and circulation is intact. The boy is immediately started on intramuscular epinephrine. (Anaphylaxis) Introduction Hypersensitivity reactions (HSR) can be considered as an overreactive immune response HSR can be classified into four categories type I, II, III, and IV type I, II, and III are antibody mediated type IV is cell mediated Speed of reaction type I HSR is immediate (fastest) type IV HSR is delayed (slowest) Type I HSR (Anaphylactic and Atopic) Mechanism of action initial exposure to an allergen causes Th2 cells to stimulate (via IL-4 and -13) B-cells to produce IgE antibodies which attaches to mast cells and basophils (these are said to be sensitized) second exposure to the allergen causes IgE cross-linking on mast cells and basophil which results in the immediate release of vasoactive amines (e.g., histamine and heparin) that can cause vascular leakage bronchoconstriction intestinal hypermotility inflammation since the antibodies are pre-formed, the reaction is immediate a few hours after the immediate response ensues, a late-phase reaction occurs which is mediated by downstream products of the arachidonic acid cascade such as prostaglandins leukotrienes Clinical disorders refer to chart Diagnostic testing allergen-specific IgE can be assessed with skin testing for allergic disease Type II HSR (Cytotoxic) Mechanism of action antibodies are directed against tissue specific antigens which can result in opsonization complement activation neutrophil and macrophage recruitment NK cell killing impair cell function if targetting a cellular receptor Clinical disorders refer to chart Diagnostic testing direct Coombs test assesses antibodies that are attached directly to the erythrocyte surface indirect Coombs test assesses antibodies that are unbound in the serum Type III HSR (Immune-Complex) Mechanism of action antibodies bind to self or foreign antigen forming immune complexes immune complexes activate the complement cascade and results in systemic manifestations Clinical disorders refer to chart Type IV HSR (Cell-Mediated) Mechanism of action T-cell-mediated tissue injury resulting from CD8+ T-cells directly killing a target cell pre-sensitized CD4+ helper T-cells are exposed to the insult, which results in cytokine release (delayed-type HSR), which leads to macrophage activation and inflammation Clinical disorders refer to chart Summary Hypersensitivity Reactions Hypersensitivity Reaction Type Pathophysiology Clinical Examples Type I (anaphylactic and atopic) Immediate Antigens cross-linkIgE antibodiestriggering vasoactive amine release (e.g., histamine) Anaphylaxis allergens bee sting food (e.g., peanuts) drugs Asthma allergens inhaled materials Allergic rhinitis allergens animals trees Type II (cytotoxic) Antibodies are directed against cell-surface antigens resulting in opsonization complement activation neutrophil and macrophage recruiting NK cell killing impairment of cellular function Autoimmune hemolytic anemia antigen erythrocyte membrane proteins Acute rheumatic fever antigen myocardial antigens via cross-reacting with S. pyogenes M protein Goodpasture syndrome antigen type IV collagen Immune thrombocytopenic purpura antigen platelet membrane proteins Myasthenia gravis antigen acetylcholine receptors Graves' disease antigen TSH receptors Erythroblastosis fetalis antigen Rh antigen Pemphigus vulgaris antigen desmosomes Type III (immune-complex) IgG antibodies complexes withself or foreign antigensresulting in complement activation Serum sickness Arthus reaction Systemic lupus erythematosis Polyarteritis nodosa Poststreptococcal glomerulonephritis Type IV (cell mediated) CD8+ T-cells directly destroy the target cell Pre-sensitized CD4+ helper T-cell releases cytokines when re-exposed to the offending material Notice this does NOT involve antibodies Type I diabetes meilltus Contact dermatitis Tuberculin test Sympathetic ophthalmia