Type I and Type II hypersensitivity reactions and their pathological presentations

1. Hypersensitivity reactions — general

Hypersensitivity reactions are normally protective immune responses that instead cause host-tissue injury, due to inadequate control or an inappropriate target. Triggering stimuli are hard to eliminate (self-antigens, persistent microbes, environmental antigens), so once started the response is difficult to terminate.

Causes: autoimmunity (loss of self-tolerance), excessive reactions to microbes (e.g. immune-complex post-streptococcal GN; T-cell injury in viral hepatitis), and reactions to environmental antigens (~20% of the population, genetic predisposition).

Type	Mechanism	Prototype disorders
I — Immediate	IgE → mast-cell mediators	Anaphylaxis, atopic asthma, allergic rhinitis
II — Antibody-mediated	IgG/IgM vs cell-surface/ECM antigen	AIHA, Goodpasture, myasthenia gravis, Graves
III — Immune complex	Ag–Ab complex deposition	SLE, serum sickness, Arthus reaction
IV — Cell-mediated	T cells / macrophages	Contact dermatitis, TB, T1DM, MS

Types I–III are antibody-mediated; type IV is T-cell mediated.

2. Type I (Immediate / anaphylactic)

IgE-mediated, occurs within minutes of antigen exposure; may be local (hay fever, asthma) or fatal (anaphylaxis).

Sequence:

1. First exposure → APC presents allergen on MHC-II to Th2 cells.
2. Th2 cytokines: IL-4 → B cells class-switch to IgE; IL-5 → recruits eosinophils; IL-13 → mucus secretion.
3. IgE binds mast cells via the Fc portion (sensitization).
4. Re-exposure cross-links IgE → mast-cell degranulation:
   • Immediate phase (5–30 min) — preformed/primary mediators: histamine, serotonin (vasodilation, ↑ permeability, smooth-muscle contraction, mucus); newly synthesized prostaglandins (bronchospasm) and leukotrienes (chemotaxis, spasm).
   • Late phase (2–8 h, days) — eosinophils, neutrophils, lymphocytes (TNF-α driven); eosinophil major basic protein → epithelial damage.

Clinical/pathology:

• Local (atopy): rhinitis, urticaria, food allergy, asthma bronchiale — reversible bronchoconstriction, airway hyperreactivity, mucus hypersecretion; features include Curschmann spirals, Charcot–Leyden crystals, eosinophilic infiltrate; chronic → emphysema → cor pulmonale.
• Systemic anaphylaxis (bee venom, penicillin): urticaria, bronchospasm, laryngeal edema, GI symptoms → anaphylactic shock; autopsy shows pulmonary edema/ARDS-type hyaline membranes.

3. Type II (Antibody-mediated / cytotoxic)

IgG/IgM bind antigens fixed on a cell surface or ECM (endogenous or exogenous, e.g. drugs). Three mechanisms:

1. Opsonization & phagocytosis — antibody/C3b-coated cells ingested via Fc/C3b receptors (e.g. autoimmune hemolytic anemia, immune thrombocytopenia).
2. Complement- & Fc-mediated inflammation — classical complement activation recruits neutrophils → tissue injury, MAC lysis (e.g. Goodpasture, pemphigus vulgaris, vasculitis).
3. Antibody-mediated cellular dysfunction — antibodies alter receptor function without injury: myasthenia gravis (anti-AChR → block), Graves (anti-TSHR → stimulation → hyperthyroidism).

Disease	Target antigen	Manifestation
Autoimmune hemolytic anemia	RBC membrane proteins	Hemolysis, anemia
Immune thrombocytopenic purpura	Platelet GpIIb/IIIa	Bleeding
Pemphigus vulgaris	Desmoglein (epidermal)	Skin bullae
Goodpasture syndrome	Basement membrane (NC1 collagen IV)	Nephritis, lung hemorrhage
Myasthenia gravis	ACh receptor	Muscle weakness
Graves disease	TSH receptor	Hyperthyroidism
Pernicious anemia	Intrinsic factor	↓ B12 absorption, anemia

Also Rh incompatibility — Rh⁻ mother sensitized by Rh⁺ fetus → IgG crosses placenta in next pregnancy → fetal hemolysis, edema, jaundice.

💡 High-yield: Type I = IgE + mast cells (Th2 → IL-4/IL-5/IL-13); immediate phase = histamine, late phase = eosinophils → anaphylaxis/asthma. Type II = IgG/IgM vs surface antigen via opsonization, complement inflammation, or receptor dysfunction (Graves = stimulating, myasthenia = blocking). Goodpasture (anti-GBM) → lung + kidney.