STEPTRACKERGENERAL PRINCIPLES | IMMUNOLOGY + PATHOLOGY | HIGH-YIELD REVIEW

Hypersensitivity Types

Four ways the immune system injures its own host — sorted by effector, timing and the test that shows it.

FOCUS ON
Type I is IgE on mast cells (minutes). Type II is antibody bound to a fixed antigen on cells or matrix. Type III is circulating immune complexes that deposit and consume complement. Type IV is T cells, with a 48–72 hour delay. Transfusion reactions are a favorite application.
TYPE
MECHANISM
TIMING · TEST
CLASSIC EXAMPLES
Type I — immediate
IgE · mast cells
First exposure: Th2 (IL-4) switches B cells to IgE, which coats mast cells. Re-exposure cross-links IgE → histamine now, then leukotrienes and eosinophils (late phase).
Minutes; late phase 2–8 h · skin prick test, ↑ IgE, ↑ tryptase after anaphylaxis
Anaphylaxis, allergic rhinitis, asthma, urticaria, food and insect-sting allergy
Type II — cytotoxic
antibody vs fixed antigen
IgG/IgM bind antigen on a cell or matrix → complement lysis, opsonization and splenic removal, ADCC by NK cells — or receptor stimulation/blockade without damage.
Hours to days · direct Coombs, tissue immunofluorescence (linear)
AIHA, ITP, HDFN, acute hemolytic transfusion reaction, Goodpasture, pemphigus, bullous pemphigoid, rheumatic fever, Graves, myasthenia gravis, pernicious anemia
Type III — immune complex
complexes deposit
Antigen–antibody complexes form in blood, lodge in vessel walls, glomeruli and joints → complement activation (↓ C3) → neutrophils damage tissue.
Local Arthus: hours · serum sickness: 5–14 days · granular immunofluorescence, ↓ complement
SLE, poststreptococcal GN, polyarteritis nodosa, cryoglobulinemia, serum sickness, Arthus reaction
Type IV — delayed
T cells, no antibody
CD4 Th1 cells release IFN-γ to activate macrophages; CD8 cells kill targets directly.
48–72 h · PPD skin test, patch test
Contact dermatitis (poison ivy, nickel), PPD, type 1 DM, MS, Hashimoto, Guillain-Barré, GVHD, acute cellular rejection
Mixed patterns
more than one type
Some diseases use several mechanisms together.
Read the dominant lesion
Hypersensitivity pneumonitis (III + IV), SLE (II cytopenias + III nephritis)
Anaphylaxis care
type I emergency
Systemic mast-cell degranulation → bronchospasm, vasodilation, airway edema.
IM epinephrine first; then antihistamines, steroids
Biphasic reaction can recur hours later

Mechanism — four effectors

I · IgE
Allergen → IgE on mast cell → cross-link → histamine, leukotrienes
II · Antibody on cell
IgG/IgM → complement, phagocytosis, ADCC, receptor effect
III · Complexes
Soluble complexes → deposit in vessels → complement ↓ → neutrophils
IV · T cell
Th1 → IFN-γ → macrophages; CD8 → direct killing

Only type IV involves no antibody. Only type III lowers serum complement consistently.

Transfusion reactions

REACTION
MECHANISM
CLUE
Allergic / anaphylactic
Type I to plasma proteins; anti-IgA in IgA deficiency
Urticaria within minutes; shock if IgA-deficient
Acute hemolytic
Type II — ABO-incompatible RBCs lysed intravascularly
Fever, flank pain, hemoglobinuria, + Coombs
Febrile nonhemolytic
Cytokines from donor leukocytes in stored blood
Fever, chills; no hemolysis → leukoreduce
TRALI
Donor anti-HLA/anti-neutrophil antibodies activate neutrophils in lung
Hypoxemia, bilateral infiltrates within 6 h
Delayed hemolytic
Anamnestic antibody to minor RBC antigens
Anemia + jaundice 1–2 weeks later

How it's tested

COMMON CONFUSIONType II: antibody binds antigen already fixed in tissue (linear IF in Goodpasture). Type III: complexes form in blood and then deposit (granular, "lumpy-bumpy" IF).
THE TRAPFever, rash, joint pain and proteinuria a week after antivenom or a new drug, with low C3, is serum sickness (type III), not an allergy (type I).
YOUR APPROACHAsk three things: how long after exposure, what effector (IgE, antibody on cell, complexes, T cells), and which test would be positive.

If you see… think…

Wheeze and hypotension minutes after peanuts → type I — epinephrine
Positive direct Coombs with hemolysis → type II
Hemoptysis + hematuria, linear IgG on GBM → Goodpasture (type II)
Fever, rash, arthralgia 7–10 days after antivenom, low C3 → serum sickness (type III)
Painful local swelling hours after a tetanus booster → Arthus reaction (type III)
Itchy vesicles 2 days after touching poison ivy → contact dermatitis (type IV)
Induration read at 48–72 h after PPD → type IV
Fever during transfusion, no hemolysis → febrile nonhemolytic — leukoreduce
Acute hypoxemia within hours of plasma transfusion → TRALI
Thyroid stimulated by antibody → Graves (type II, non-cytotoxic)