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

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

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

Celiac Disease (see Celiac Disease)
Contact Dermatitis-Allergic Type (see Contact Dermatitis-Allergic): T-cells target modified skin proteins
- Chemicals
  - Formaldehyde (see Formaldehyde)
- Drugs
  - Benzocaine (see Benzocaine)
- Metals
  - Gold (see Gold)
- Plants
  - Rhus Dermatitis (Poison Ivy, etc)
  - Compositae Dermatitis
Exanthematous Drug Eruption (Morbilliform Drug Eruption, Maculopapular Drug Eruption) (see Exanthematous Drug Eruption)
- Physiology: many (but not all) exanthematous drug eruptions involve a type IV hypersensitivity mechanism
Guillain-Barre Syndrome (GBS) (see Guillain-Barre Syndrome)
Hashimoto’s Thyroiditis (see Hashimoto’s Thyroiditis)
Hypersensitivity Vasculitis (see Vasculitis): involves both type III and type IV mechanisms
Inflammatory Bowel Disease (IBD) (see 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): T-cells target pancreatic islet cell antigens
Multiple Sclerosis (see Multiple Sclerosis): T-cells target myelin proteins
Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis): T-cells target unknown antigens in joint
Temporal Arteritis (Giant Cell Arteritis) (see Temporal Arteritis)
Toxic Shock Syndrome: T-cells target polyclonal microbial superantigens
- Staphylococcal Toxic Shock Syndrome (see Staphylococcal Toxic Shock Syndrome)
- Streptococcal Toxic Shock Syndrome (see Streptococcal Toxic Shock Syndrome)
Transfusion-Associated Graft vs Host Disease (see Transfusion-Associated Graft vs Host Disease)
Tuberculin Skin Test (Purified Protein Derivative = PPD Skin Test) (see Tuberculin Skin Test)
- Tuberculin Skin Test Turns Positive Approximately 2-8 Weeks After Mycobacterium Tuberculosis Infection (see Tuberculosis)
Tuberculosis (see Tuberculosis): T-cells target microbial proteins
Viral Hepatitis
- Hepatitis B (see Hepatitis B Virus): T-cells target viral proteins
- Hepatitis C (see Hepatitis C Virus): T-cells target viral proteins

Typical Treatments

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

References

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