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
- Mast Cell-Mediated Mechanism
- Anaphylaxis Can Be Caused by Multiple Mechanisms
- 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
- Mast Cell-Mediated Mechanism
- Angioedema Can Be Caused by Multiple Mechanisms
- 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
- Mast Cell-Mediated Mechanism
- Urticaria Can Be Caused by Multiple Mechanisms
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
- Chemicals
- 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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