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, [[Allergic Rhinitis]])
  • Allergic Urticaria (IgE-Dependent Urticaria) (see Urticaria, [[Urticaria]])
  • Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])
  • Angioedema (see Angioedema, [[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 Metabiolism
        • 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, [[Asthma]])
    • Note: some cases of asthma are not associated with elevated IgE, although all are associated with mast cell activation (the mechanism of mast cell activation in these non-IgE cases is unclear)
  • Atopic Dermatitis (see Atopic Dermatitis, [[Atopic Dermatitis]])
  • Food Allergy (see Food Allergy, [[Food Allergy]])
  • Urticaria (see Urticaria, [[Urticaria]])
    • Note: urticaria may be mediated by an IgE-Mediated mechanism (as the other conditions listed here) or alternatively, via other mechanisms (non-immunologic direct mast cell or basophil activation, etc)

Typical Treatments

  • Antihistamines (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]])
    • Pharmacology: antihistamine
  • Omalizumab (Xolair) (see Omalizumab, [[Omalizumab]])
    • Pharmacology: anti-IgE
  • Corticosteroids (see Corticosteroids, [[Corticosteroids]])
    • Pharmacology: anti-inflammatory
  • Cromolyn (see Cromolyn, [[Cromolyn]])
    • Pharmacology: mast cell stabilizer
  • Desensitization: repeated administration of small doses of allergens administered -> may induce tolerance
  • Epinephrine (see Epinephrine, [[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 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, [[Hemolytic Anemia]]): antibody against RBC membrane proteins
  • Bullous Pemphigoid (see Bullous Pemphigoid, [[Bullous Pemphigoid]])
  • Erythroblastosis Fetalis (Hemolytic Disease of the Newborn)
  • Goodpasture’s Syndrome (see Goodpasture’s Syndrome, [[Goodpastures Syndrome]]): antibody against non-collagenous protein in basement membrane of lung alveoli and renal glomeruli
  • Grave’s Disease (see Hyperthyroidism, [[Hyperthyroidism]]): antibody against TSH receptor
  • Immune Thrombocytopenic Purpura (ITP) (see Immune Thrombocytopenic Purpura, [[Immune Thrombocytopenic Purpura]]): antibody against platelet membrane protein (IIb/IIIa intgegrin)
  • Myasthenia Gravis (MG) (see Myasthenia Gravis, [[Myasthenia Gravis]]): antibody against acetylcholine receptor
  • Pemphigus Vulgaris (see Pemphigus Vulgaris, [[Pemphigus Vulgaris]]): antibody against epidermal cadherin (in intracellular junctions between epidermal cells)
  • Pernicious Anemia (see Pernicious Anemia, [[Pernicious Anemia]]): antibody against intrinsic factor of gastric parietal cells
  • Rheumatic Fever (see Rheumatic Fever, [[Rheumatic Fever]])

Typical Treatments

  • Anti-CD20 Therapy (see Anti-CD20 Therapy, [[Anti-CD20 Therapy]])
    • Pharmacology: depletes B cells
  • Corticosteroids (see Corticosteroids, [[Corticosteroids]])
    • Pharmacology: anti-inflammatory
  • Plasmapheresis (see Plasmapheresis, [[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

  • Henoch-Schonlein Purpura (see Henoch-Schonlein Purpura, [[Henoch-Schonlein Purpura]])
  • Hypersensitivity Pneumonitis (HP) (see Hypersensitivity Pneumonitis, [[Hypersensitivity Pneumonitis]])
  • Hypersensitivity Vasculitis (see Vasculitis, [[Vasculitis]]): involves both type III and type IV mechanisms
  • Polyarteritis Nodosa (PAN) (see Polyarteritis Nodosa, [[Polyarteritis Nodosa]]): antibody against hepatitis B surface antigen
  • Post-Streptococcal Glomerulonephritis: antibody against Streptococcal cell wall antigen
  • Reactive Arthritis (see Reactive Arthritis, [[Reactive Arthritis]])
  • Serum Sickness (see Serum Sickness, [[Serum Sickness]]): antibody against various antigens
  • Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]]): antibodies against DNA, nucleoproteins, etc

Typical Treatments

  • Anti-CD20 Therapy (see Anti-CD20 Therapy, [[Anti-CD20 Therapy]])
    • Pharmacology: depletes B cells
  • Corticosteroids (see Corticosteroids, [[Corticosteroids]])
    • Pharmacology: anti-inflammatory
  • Plasmapheresis (see Plasmapheresis, [[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

  • Celiac Disease (see Celiac Disease, [[Celiac Disease]])
  • Contact Dermatitis-Allergic Type (see Contact Dermatitis-Allergic, [[Contact Dermatitis-Allergic]]): T-cells target modified skin proteins
    • Chemicals: Formaldehyde, etc
    • Drugs: Benzocaine, etc
    • Metals: Gold, etc
    • Plants: Rhus Dermatitis (Poison Ivy, etc), Compositae dermatitis, etc
  • Guillain-Barre Syndrome (GBS) (see Guillain-Barre Syndrome, [[Guillain-Barre Syndrome]])
  • Hashimoto’s Thyroiditis (see Hashimoto’s Thyroiditis, [[Hashimotos Thyroiditis]])
  • Hypersensitivity Vasculitis (see Vasculitis, [[Vasculitis]]): involves both type III and type IV mechanisms
  • Inflammatory Bowel Disease (IBD) (see Inflammatory Bowel Disease, [[Inflammatory Bowel Disease]]): T-cells target against uknown antigens (there is a possible role of intestinal microbial flora in this process)
  • Insulin-Dependent Diabetes Mellitus (IDDM) (see Diabetes Mellitus, [[Diabetes Mellitus]]): T-cells target pancreatic islet cell antigens
  • Multiple Sclerosis (see Multiple Sclerosis, [[Multiple Sclerosis]]): T-cells target myelin proteins
  • Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]]): T-cells target unknown antigens in joint
  • Temporal Arteritis (Giant Cell Arteritis) (see Temporal Arteritis, [[Temporal Arteritis]])
  • Toxic Shock Syndrome: T-cells target polyclonal microbial superantigens
  • Transfusion-Associated Graft vs Host Disease (see Transfusion-Associated Graft vs Host Disease, [[Transfusion-Associated Graft vs Host Disease]])
  • Tuberculin Skin Test (Purified Protein Derivative = PPD Skin Test) (see Tuberculin Skin Test, [[Tuberculin Skin Test]])
    • Tuberculin Skin Test Turns Positive Approximately 2-8 Weeks After Mycobacterium Tuberculosis Infection (see Tuberculosis, [[Tuberculosis]])
  • Tuberculosis (see Tuberculosis, [[Tuberculosis]]): T-cells target microbial proteins
  • Viral Hepatitis
    • Hepatitis B (see Hepatitis B Virus, [[Hepatitis B Virus]]): T-cells target viral proteins
    • Hepatitis C (see Hepatitis C Virus, [[Hepatitis C Virus]]): T-cells target viral proteins

Typical Treatments

  • Corticosteroids (see Corticosteroids, [[Corticosteroids]])
    • Pharmacology: anti-inflammatory
  • Anti-Tumor Necrosis Factor-α Therapy (Anti-TNFα Therapy) (see Anti-Tumor Necrosis Factor-α Therapy, [[Anti-Tumor Necrosis Factor-α Therapy]])
    • Pharmacology: anti-TNFα
  • Cyclosporine-A (see Cyclosporine A, [[Cyclosporine A]])
    • Pharmacology: inhibits T cell responses

References

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