What are the different types of hypersensitivity reactions?

Types of Hypersensitivity Reactions

Hypersensitivity reactions are classified into four main types according to the Gell and Coombs classification system: Type I (IgE-mediated), Type II (antibody-mediated cytotoxic), Type III (immune complex-mediated), and Type IV (delayed T cell-mediated). 1

Type I: IgE Antibody-Mediated Reactions

• Type I reactions are immediate hypersensitivity responses where allergens cross-link IgE antibodies bound to mast cells and basophils, triggering degranulation within minutes to hours (typically 1-6 hours) after exposure 2

• Clinical manifestations include:

  • Anaphylaxis (severe, life-threatening systemic reaction) 1, 2
  • Urticaria, pruritus, flushing, and angioedema 2
  • Bronchospasm, wheezing, and respiratory distress 2
  • Hypotension, tachycardia, and potential cardiovascular collapse 2

• Key mediators: Histamine (released within 5 minutes, elevated for 15-60 minutes) and tryptase (measurable 15 minutes to 3 hours after reaction onset) 2

• First-line treatment is epinephrine 0.01 mg/kg intramuscularly (maximum 0.5 mg adults, 0.3 mg children), with antihistamines and corticosteroids as adjuncts 2

Type II: Antibody-Mediated Cytotoxic Reactions

• Type II reactions involve IgG or IgM antibodies directed against cell surface antigens, leading to cell destruction 1

• Clinical examples include:

  • Hemolytic anemia 1
  • Thrombocytopenia 1
  • Blood transfusion reactions 1

• The classification has been refined to include Type IIa (cytotoxic) and Type IIb (antibody-mediated cell stimulation, such as Graves disease) 3

Type III: Immune Complex-Mediated Hypersensitivity

• Type III reactions result from deposition of antigen-antibody immune complexes (IgG/IgM) in tissues, causing inflammation and tissue damage 1

• Clinical manifestations include:

  • Serum sickness 1
  • Vasculitis 1

Type IV: Delayed T Cell-Mediated Responses

• Type IV reactions are delayed hypersensitivity responses occurring hours to days after antigen exposure, mediated by T lymphocytes rather than antibodies 4, 3

• The modern classification divides Type IV into four subtypes: 3, 5

  • Type IVa: CD4+ Th1 lymphocyte-mediated with macrophage activation (contact dermatitis, granuloma formation) 3, 5
  • Type IVb: CD4+ Th2 lymphocyte-mediated with eosinophilic involvement (chronic asthma, allergic rhinitis, maculopapular exanthema with eosinophilia) 3, 5
  • Type IVc: Cytotoxic CD8+ T lymphocyte-mediated with perforin-granzyme B involvement (Stevens-Johnson syndrome, toxic epidermal necrolysis) 3, 5
  • Type IVd: T lymphocyte-driven neutrophilic inflammation (acute generalized exanthematous pustulosis, pustular psoriasis) 3, 5

• Clinical presentations include:

  • Allergic contact dermatitis 1
  • Maculopapular exanthema 1, 4
  • Severe cutaneous adverse reactions (SJS/TEN, DRESS) 4
  • Erythema multiforme 1

• Type IV reactions are NOT amenable to desensitization, and drugs causing severe T-cell mediated reactions must be completely avoided due to long-lasting memory T-cell responses 4

Important Clinical Distinctions

• True hypersensitivity reactions must be distinguished from non-immune-mediated reactions including pseudo-allergic (anaphylactoid) reactions that cause direct mast cell degranulation without IgE involvement 1

• Timing is critical for classification: immediate reactions occur within 1 hour (typically Type I), while delayed reactions occur after 1 hour and commonly manifest after many days (typically Type IV) 6

• Many diseases involve multiple types of hypersensitivity simultaneously, making the clinical picture more complex than the traditional classification suggests 7