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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-link IgE antibodies triggering
    • 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 with self or foreign antigens resulting 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
 

References

 

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