Immune Hypersensitivity Reactions

Definition

  • Immune Hypersensitivity Reaction: immune responses which result in tissue damage

Type I Hypersensitivity = Immediate Hypersensitivity (Allergy)

Mechanism

  • Initial Encounter with Allergen (Pollen, Food, Insect Venom, Animal Dander, Drugs): leads to sensitization (which is often asymptomatic)
  • Repeat Encounter with Allergen in Allergic Person: leads to activation of TH2 Cells -> IL-4 and IL-13 secretion -> IgE antibody directed against environmental antigen -> IgE binds to mast cells -> mast cell release of vasoactive amines/lipid mediators/cytokines -> recruitment of leukocytes (eosinophils, neutrophils, and Th2 cells)
    • Early Phase (Within Minutes): increased vascular permeability and smooth muscle contraction
    • Late Phase (Within Hours): cytokine-mediated inflammation with eosinophils and neutrophils (cytokine-mediated inflammation) -> tissue injury

Typical Diseases

  • Allergic Rhinitis (see Allergic Rhinitis)
  • Anaphylaxis (see Anaphylaxis)
    • Anaphylaxis Can Be Caused by Multiple Mechanisms
      • Mast Cell-Mediated Mechanism
        • IgE-Mediated Mast Cell Activation (Type I Hypersensitivity): similar to the other type I hypersensitivity conditions listed here
        • Immunologic Non-IgE-Mediated Mast Cell Activation
        • Non-Immunologic Direct Mast Cell/Basophil Activation
      • Other
  • Angioedema (see Angioedema)
    • Angioedema Can Be Caused by Multiple Mechanisms
      • Mast Cell-Mediated Mechanism
        • IgE-Mediated Mast Cell Activation (Type I Hypersensitivity): similar to the other type I hypersensitivity conditions listed here
        • Immunologic Non-IgE-Mediated Mast Cell Activation
        • Non-Immunologic Direct Mast Cell/Basophil Activation
        • Altered Arachidonic Acid Metabolism
        • Other
      • Bradykinin-Mediated Mechanism
        • Altered Bradykinin Metabolism
        • Hereditary Angioedema (Hereditary C1 Inhibitor Deficiency/Dysfunction)
        • Acquired C1 Inhibitor Deficiency (Acquired Angioedema)
      • Unknown Mechanism
        • Infection
        • Drug/Toxin
        • Other
  • Asthma (see Asthma)
    • While Some Cases of Asthma are Not Associated with Elevated IgE, All Cases of Asthma are Associated with Mast Cell Activation (The mechanism of Mast Cell Activation in These Non-IgE Cases is Unclear)
  • Atopic Dermatitis (see Atopic Dermatitis)
  • Food Allergy (see Food Allergy)
  • Urticaria (see Urticaria)
    • Urticaria Can Be Caused by Multiple Mechanisms
      • Mast Cell-Mediated Mechanism
        • IgE-Mediated Mast Cell Activation (Type I Hypersensitivity): similar to the other type I hypersensitivity conditions listed here
        • Immunologic Non-IgE-Mediated Mast Cell Activation
        • Non-Immunologic Direct Mast Cell/Basophil Activation
        • Altered Arachidonic Acid Metabolism
      • Infection
      • Physical Stimuli
      • Autoimmune Disease
      • Other

Typical Treatments

  • Antihistamines (see H1-Histamine Receptor Antagonists)
    • Pharmacology: antihistamine
  • Omalizumab (Xolair) (see Omalizumab)
    • Pharmacology: anti-IgE
  • Corticosteroids (see Corticosteroids)
    • Pharmacology: anti-inflammatory
  • Cromolyn (see Cromolyn)
    • Pharmacology: mast cell stabilizer
  • Desensitization: repeated administration of small doses of allergens administered -> may induce tolerance
  • Epinephrine (see Epinephrine)
    • Clinical Use: commonly used in anaphylaxis
    • Pharmacology: vasoconstriction, bronchodilation, etc

Type II Hypersensitivity = Antibody-Mediated

Mechanism

  • IgM/IgG Antibodies Against Cell Surface or Extracellular Matrix Antigens: leads to complement + Fc receptor-mediated recruitment and activation of neutrophils/macrophages -> opsonization and phagocytosis of cells
    • Abnormalities in cellular function (hormone receptor signaling)

Examples

  • Acute Hemolytic Transfusion Reaction (see Acute Hemolytic Transfusion Reaction)
  • Acute Rheumatic Fever: antibody against Streptococcal cell wall antigen (this antibody cross-reacts with myocardial antigen)
  • Autoimmune Hemolytic Anemia (see Hemolytic Anemia): antibody against RBC membrane proteins
  • Bullous Pemphigoid (see Bullous Pemphigoid)
  • Erythroblastosis Fetalis (Hemolytic Disease of the Newborn)
  • Goodpasture’s Syndrome (see Goodpasture’s Syndrome): antibody against non-collagenous protein in basement membrane of lung alveoli and renal glomeruli
  • Grave’s Disease (see Hyperthyroidism): antibody against TSH receptor
  • Immune Thrombocytopenic Purpura (ITP) (see Immune Thrombocytopenic Purpura): antibody against platelet membrane protein (IIb/IIIa intgegrin)
  • Myasthenia Gravis (MG) (see Myasthenia Gravis): antibody against acetylcholine receptor
  • Pemphigus Vulgaris (see Pemphigus Vulgaris): antibody against epidermal cadherin (in intracellular junctions between epidermal cells)
  • Pernicious Anemia (see Pernicious Anemia): antibody against intrinsic factor of gastric parietal cells
  • Rheumatic Fever (see Rheumatic Fever)

Typical Treatments

  • Anti-CD20 Therapy (see Anti-CD20 Therapy)
    • Pharmacology: depletes B cells
  • Corticosteroids (see Corticosteroids)
    • Pharmacology: anti-inflammatory
  • Plasmapheresis (see Plasmapheresis)
    • Pharmacology: decreases antibody and immune complex levels

Type III Hypersensitivity = Immune Complex-Mediated

Mechanism

  • Immune Complexes of Circulating Antigens + IgM/IgG Antibodies Deposited in Vascular Basement Membrane: leads to complement + Fc receptor-mediated recruitment and activation of neutrophils/macrophages

Examples

Typical Treatments

  • Anti-CD20 Therapy (see Anti-CD20 Therapy)
    • Pharmacology: depletes B cells
  • Corticosteroids (see Corticosteroids)
    • Pharmacology: anti-inflammatory
  • Plasmapheresis (see Plasmapheresis)
    • Pharmacology: decreases antibody and immune complex levels

Type IV Hypersensitivity = T Cell-Mediated

Mechanism

  • CD4 Cells (Delayed-Type Hypersensitivity) and CD8 Cells (T Cell-Mediated Cytolysis of Host Cells): leads to macrophage activation and cytokine-mediated inflammation -> direct target cell lysis and cytokine-mediated inflammation

Examples

Typical Treatments

References

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