Hypersensitivity refers to exaggerated or harmful immune responses that damage host tissues. Unlike normal protective immunity, hypersensitivity reactions are inappropriate, excessive and may sometimes be fatal. They are classified into four major types based on the immune mechanism involved.
Type I Hypersensitivity (Immediate / IgE-Mediated)
This reaction occurs when an allergen binds to IgE antibodies attached to mast cells and basophils. It produces symptoms within minutes.
Sensitization Phase
- Initial exposure to the allergen activates TH2 cells and B cells.
- B cells produce allergen-specific IgE.
- IgE binds to mast cells (no symptoms yet).
Activation Phase
- Re-exposure to the allergen cross-links IgE on mast cells.
- Mast cells degranulate immediately.
- Mediators released: histamine, proteases, TNF-α, leukotrienes, prostaglandins.
Effector Phase
- Histamine → vasodilation, increased permeability, mucus secretion, bronchoconstriction.
- Leukotrienes and prostaglandins → prolonged bronchoconstriction.
- Cytokines → attract eosinophils and neutrophils.
Clinical Examples
- Allergic rhinitis: Sneezing, itching, runny nose due to airborne allergens.
- Asthma: Reversible airway obstruction and inflammation.
- Food allergy: Vomiting, diarrhea, hives due to mast cell activation in GIT/skin.
- Anaphylaxis: Life-threatening systemic mast cell degranulation causing bronchospasm and shock.
Diagnosis
- Skin prick/scratch test → wheal and flare reaction within 30 mins.
- Serum IgE tests (RAST or ELISA).
Treatment
- Avoid allergen exposure.
- Desensitization (allergen immunotherapy).
- Anti-IgE monoclonal antibody (omalizumab).
- Mast cell stabilizers (cromolyn sodium).
- Antihistamines (H1 and H2 blockers).
- Epinephrine → drug of choice for anaphylaxis.
Type II Hypersensitivity (Antibody-Mediated)
This involves IgG or IgM antibodies directed against antigens on cell surfaces. The target cell is destroyed by:
- Complement-mediated lysis
- Antibody-dependent cytotoxicity (NK cells)
- Phagocytosis by macrophages/neutrophils
Clinical Examples
- Drug-induced reactions: Penicillin or cephalosporin binding to RBCs → hemolytic anemia; quinine → thrombocytopenia.
- Blood transfusion reaction: ABO incompatibility.
- Rh incompatibility (Hemolytic disease of newborn): Rh-negative mother sensitized to Rh-positive fetus.
Rh Disease Prevention
Rh-negative mothers receive RhoGAM (anti-D immunoglobulin) during late pregnancy and after delivery to prevent sensitization.
Type III Hypersensitivity (Immune Complex–Mediated)
This reaction occurs when antigen–antibody complexes (IgG or IgM) form in excess and deposit in small blood vessels. Complement activation causes inflammation and tissue injury.
Clinical Examples
- Arthus Reaction: Local reaction after injected antigen in a sensitized person → redness, swelling within 3–8 hrs.
- Serum Sickness: Systemic complex deposition after injection of foreign proteins (e.g., antivenom). Symptoms: fever, joint pain, urticaria, enlarged spleen.
- Hypersensitivity pneumonitis (Farmer’s lung): Inhaled fungal spores cause IgE and IgG formation, leading to lung inflammation and fibrosis.
Treatment
- Avoid exposure to the antigen.
- High-dose corticosteroids for severe lung involvement.
- Supportive therapy as needed.
Type IV Hypersensitivity (Delayed-Type / T Cell–Mediated)
This response is mediated by T lymphocytes rather than antibodies. It appears 48–72 hours after exposure.
Clinical Examples
- Tuberculin (Mantoux) Test: Redness and induration 48–72 hrs after PPD injection.
- Contact dermatitis: Caused by nickel, rubber, latex, lanolin, plant chemicals (e.g., poison ivy). Symptoms: red rash, blisters, itching.
- Celiac disease: T cell–mediated response to gluten (HLA-DQ2/DQ8 linked). Causes villous atrophy, diarrhea, anemia.
Treatment
- Topical steroids for mild dermatitis.
- Systemic corticosteroids for severe cases.
- Gluten-free diet for celiac disease.
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