Hypersensitivity Reactions

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Hypersensitivity Reactions

• Gell and Coombs classification
• Type I IgE mediated (allergy)
• Type II Antibody-mediated cytotoxic
• Type III Immune Complex mediated
• Type IV Delayed-Type Hypersensitivity (DTH)
• Types I, II and III are immediate
• Type IV is delayed

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Type I Hypersensitivity

• Antigens are called allergens
• Unknown why people get allergies, but there is a
  strong genetic predisposition (called atopy)
• Hallmark is inappropriate production of IgE
  against allergens that cause mast cell
  degranulation (see fig 15-2)
• Normally IgE/mast cell activity should be
  directed against parasitic infections

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Type I Hypersensitivity

• Mediators of Type I hypersensitivites
• Mast cell granule contents (early effects)
• Histamine and Heparin - ? vascular permeability,
  smooth muscle contraction (intestines, bronchi),
  mucus secretion
• Chemotactic factors attract eosinophils and
  neutrophils
• Proteases mucus secretion, complement
  activation, degradation of blood vessel basement
  membrane
• Later Effects
• Leukotrienes and prostaglandins secreted after
  tissue disruption caused by mast cell
  degranulation, effects are similar to histamine
• Arrival of proinflammatory eosinophils and
  neutrophils

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Clinical Manifestations of Type I

• Systemic anaphylaxis
• Allergen gets into the blood stream
• Dyspnea, ?BP, bronchole constriction, GI and
  bladder smooth muscle contration, shock, death
  within minutes if untreated
• Treatment - epinephrine
• Allergic rhinitis (hay fever)
• Inhaled allergen triggers reaction in nasal
  mucosa
• Watery exudate from nose, eyes, upper respiratory
  tract, sneeezing and coughing

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Clinical Manifestations of Type I

• Asthma
• Allergic asthma due to inhaled airborne
  allergens (pollens, dust, fumes, etc)
• Intrinsic asthma triggered by cold, exercise
• Reaction develops in lower respiratory tract
• Bronchoconstriction, airway edema, mucus
  secretion, inflammation
• Food allergies
• Ingestion of allergen
• Vomiting and diarrhea
• If allergens are absorbed into bloodstream,
  reactions can occur where allergen deposits
• asthma-like symptoms
• Urticaria (hives, wheal flare response)

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Clinical Manifestations of Type I

• Atopic Dermatitis (allergic eczema)
• Often occurs in young children
• Red skin rash
• Strong hereditary predisposition

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Type I Hypersensitivity

• Skin testing
• Potential allergens are injected or scratched
  into the skin
• If the patient is allergic a wheal flare
  response occurs
• RIST radioimmunosorbent test similar to RIA,
  non-invasive way to identify allergies

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Type I Hypersensitivity

• Treatment
• Avoid allergen if possible
• Antihistamines, or anti-prostaglandins
• Hyposensitization injections of low doses of
  allergen may cause a shift from IgE to IgG as the
  dominant antibody formed.

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Type II Hypersensitivity

• Antibody-mediated Cytotoxic HS
• Antibodies (IgM or IgG) bind to cell surface
  antigens. Antigen/antibody complex may lead to
• Complement activation ? lysis
• ADCC
• Opsonization ? phagocytosis
• These are normal reactions, but when they cause
  unwarranted tissue damage, they are considered a
  hypersensitivity.

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Type II Hypersensitivity

• Examples of Type II HS
• Transfusion reactions
• To ABO blood groups
• To other RBC blood groups
• Hemolytic disease of the newborn
  (erythroblastosis fetalis)
• Drug-induced hemolytic anemia (penicillin)

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Type III Hypersensitivity

• Immune Complex Disease
• Antibody (IgG) / attaching to soluble antigen
  leads to complex formation
• Immune complexes may deposit in
• Blood vessel walls (vasculitis)
• Synovial joints (arthritis)
• Glomerular basement membrane (glomerulonephritis)
• Choroid plexus

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Type III Hypersensitivity

• Damage occurs due to
• Anaphylatoxin release due to complement
  activation (C3a, C5a) which then attracts
  neutrophils, and causes mast cell degranulation
• Neutrophils have trouble phagocytosing stuck
  immune complexes so they release their granule
  contents leading to more inflammation
• Platelet aggregation also results from complement
  activation
• These effects are also known as the Arthus
  reaction

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Type III Hypersensitivity

• Localized reactions
• edema and redness (erythema) and tissue necrosis
  of the affected tissue
• Can occur in the skin following insect bites
• Can occur in the lungs
• E.g. farmers lung from inhaling particles from
  moldy hay

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Type III Hypersenstivity

• Generalized reactions
• Serum sickness (following treatment with
  antiserum to a toxin)
• Autoimmune diseases
• SLE
• Rheumatoid arthritis
• Drug reactions (penicillin)
• Infectious diseases
• Meningitis, hepatitis, malaria, mono etc.

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Type IV Hypersensitivity

• Delayed type hypersensitivity (DTH)
• TH cells that have been sensitized by an
  antigen develop a TH1 and (sometimes a TC
  response) leading to macrophage recruitment and
  activation.
• First noticed with reaction to tuberculosis
  bacteria (tuberculin reaction)
• Hallmarks of type IV is the large number of
  macrophages at the reaction site, and that it
  takes an average of 24 hrs to manifest after
  repeat exposure.

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