How hypersensitivity is tested on Step 1

Identify the effector (IgE, antibody against a fixed antigen, immune complexes, or T cells).

HypersensitivityType IIgE, mast cells;minutesType IIAntibody vs cellantigenType IIIImmune complexesType IVT cells; days
Memory aid ACID: Anaphylactic, Cytotoxic, Immune complex, Delayed. Types I–III are antibody mediated; type IV is cell mediated.
TypeMechanismClassic examples
IIgE on mast cells; histamine, leukotrienesAnaphylaxis, allergic rhinitis and asthma, urticaria
IIIgG/IgM against cell-surface or matrix antigenHemolytic transfusion reaction, autoimmune hemolytic anemia, ITP, Goodpasture, rheumatic fever, pemphigus vulgaris, Graves, myasthenia gravis
IIICirculating immune complexes deposit and activate complementSLE, poststreptococcal GN, serum sickness, Arthus reaction, polyarteritis nodosa
IVSensitized CD4 and CD8 T cellsContact dermatitis, PPD test, type 1 diabetes, Hashimoto thyroiditis, multiple sclerosis

Type II reactions affect a specific tissue (where the antigen is); type III reactions affect sites where complexes lodge (skin, joints, kidneys, vessels).

Distinguishing types II and III

Both use antibodies; where the antigen is decides the type.

Type IIAntigen fixed on cells or matrixLinear immunofluorescence (Goodpasture)Direct Coombs + in hemolysisCan block or stimulate receptorsTissue-specificType IIIAntigen–antibody complexes circulateGranular ("lumpy-bumpy") depositsLow complement levelsVasculitis, arthritis, nephritisSystemicvs
Serum sickness (fever, rash, arthralgia, proteinuria about 1–2 weeks after a foreign protein or drug) is a systemic type III reaction; the Arthus reaction is a local one at an injection site.

Transplant rejection

Timing points to the mechanism.

When rejection occurs after transplantMinutesDaysWeeksMonthsYearsHyperacuteAntibodiesAcuteT cells ± antibodyChronicFibrosisGVHDDonor T cells
Rejection timing. Approximate windows; acute rejection is most common in the first months.
TypeMechanismFeatures
HyperacutePreformed recipient antibodies (ABO, HLA) → type IIGraft thrombosis and ischemia within minutes; prevented by crossmatching
AcuteCD8 T cells against donor MHC; donor-specific antibodies may contributeInterstitial lymphocytes, vasculitis; reversible with immunosuppression
ChronicOngoing T-cell and antibody injuryVascular smooth muscle proliferation, fibrosis; e.g., bronchiolitis obliterans (lung), accelerated coronary disease (heart)
GVHDDonor T cells attack recipient tissuesRash, jaundice, diarrhea after bone marrow or stem cell transplant

Irradiating blood products prevents transfusion-associated GVHD in immunocompromised recipients.

Treatment links

Match therapy to the immune effector.

  • Anaphylaxis: IM epinephrine first; antihistamines and steroids are adjuncts. Elevated serum tryptase supports mast cell activation.
  • Antibody-mediated disease: plasmapheresis or IVIG can remove or block pathogenic antibodies.
  • Rejection prevention: calcineurin inhibitors (cyclosporine, tacrolimus), antimetabolites (mycophenolate, azathioprine), mTOR inhibitors (sirolimus), and corticosteroids.

Worked example

Classify a drug reaction.

functions Worked example — rash after antivenom

Ten days after receiving antivenom, a patient develops fever, an itchy rash, joint pain, and proteinuria. Serum C3 is low. What type of hypersensitivity is this?

  1. Symptoms began about 1–2 weeks after exposure to a foreign protein.
  2. Antibodies formed against the antivenom proteins and created circulating immune complexes.
  3. The complexes deposited in skin, joints, and kidneys and consumed complement (low C3).
  4. This is serum sickness, a systemic type III reaction.

Answer. Type III hypersensitivity (serum sickness).