Type I Hypersensitivity Reactions – Key Mechanisms and Mediators

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Overview:
    • Type I (immediate) hypersensitivity:
      • Is the classic IgE – mediated allergic reaction
    • Sensitized individuals produce allergen – specific IgE:
      • That binds to FcεRI receptors on mast cells and basophils:
        • On re-exposure, cross-linking of IgE:
          • Triggers rapid release of pre-formed mediators and synthesis of secondary mediators:
            • Producing the acute allergic response
  • Key Chemical Mediators:
    • Histamine:
      • Source:
        • Mast cells (tissue)
        • Basophils (blood)
      • Actions: 
        • Vasodilation
        • Increased vascular permeability:
          • Leading to tissue edema and post-capillary venule leakage
        • Smooth-muscle contraction:
          • Bronchospasm
        • Pruritus
    • Bradykinin:
      • Formation: 
        • Generated from high-molecular-weight kininogen by kallikrein
      • Actions: 
        • Peripheral vasodilation
        • Marked increase in vascular permeability
        • Pain
        • Pulmonary vasoconstriction
        • Bronchoconstriction
      • Clinical link: 
        • Major mediator of hereditary or ACE-inhibitor – induced angioedema.
    • Leukotrienes (C₄, D₄, E₄):
      • Potent, sustained bronchoconstrictors
      • Increase vascular permeability
      • Promote mucus secretion
    • Prostaglandin D₂ and platelet-activating factor:
      • Contribute to vasodilation, bronchospasm, and recruitment of inflammatory cells
  • Regulation by ACE:
    • Angiotensin-converting enzyme (ACE):
      • Highly expressed on pulmonary and endothelial surfaces
      • Inactivates bradykinin and other kinins,:
        • Limiting edema
      • ACE inhibition (e.g., by ACE-inhibitor medications):
        • Elevates bradykinin levels:
          • Predisposing to angioedema with airway compromise
  • Clinical Correlates:
    • Immediate phase (minutes): 
      • Mast-cell histamine release → urticaria, bronchospasm, hypotension (anaphylaxis)
    • Late phase (hours): 
      • Cytokine and leukotriene–driven influx of eosinophils and neutrophils:
        • Sustained inflammation (e.g., asthma exacerbation)
  • Key Takeaway:
    • Type I hypersensitivity hinges on IgE-primed mast cells and basophils as the principal histamine sources:
      • With histamine as the rapid primary effector
    • Bradykinin amplifies vascular leakage and pain but is normally curtailed by ACE:
      • Impaired degradation (e.g., ACE-inhibitor therapy) can precipitate angioedema independent of histamine
Rodrigo Arrangoiz, MD (Oncology Surgeon)
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Published by Rodrigo Arrangoiz MS, MD, FACS, FSSO

My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida. I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016. Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida. Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.

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