STEPTRACKERIMMUNOLOGY + NEPHROLOGY + HEMATOLOGY | HYPERSENSITIVITY | HIGH-YIELD REVIEW

Type II & Type III Hypersensitivity

Type II: antibody binds an antigen fixed on a cell or tissue. Type III: antibody and soluble antigen form complexes that lodge in vessels and glomeruli.

FOCUS ON
Type II (IgG/IgM vs fixed antigen) — three mechanisms: (1) opsonization/phagocytosis or complement lysis (autoimmune hemolytic anemia, ITP, transfusion reactions, hemolytic disease of the newborn); (2) inflammation via complement and Fc receptors (Goodpasture — linear IF, acute rheumatic fever, pemphigus vulgaris, bullous pemphigoid); (3) receptor dysfunction without damage (Graves — stimulating TSH-R; myasthenia gravis — blocking AChR; pernicious anemia; type B insulin resistance). Direct Coombs ⁺ for RBC antibodies. Type III (immune complexes): SLE, PSGN, PAN (HBV), cryoglobulinemia (HCV), serum sickness (fever, rash, arthralgia, ↓ C3 ~1–2 weeks after foreign protein or drugs), Arthus reaction (local, hours after intradermal booster); granular ("lumpy-bumpy") IF, ↓ complement, vasculitis.
DISEASE
TYPE · TARGET
MECHANISM
CLUE
Autoimmune hemolytic anemia
II · RBC antigens
Warm IgG → splenic removal (spherocytes) · cold IgM → complement
Direct Coombs ⁺
Immune thrombocytopenia
II · GPIIb/IIIa
IgG-coated platelets cleared by splenic macrophages
Isolated low platelets, normal marrow
Hemolytic disease of the newborn
II · fetal Rh(D) RBCs
Maternal anti-D IgG crosses placenta
Prevented by anti-D immune globulin (RhoGAM)
Goodpasture (anti-GBM) disease
II · type IV collagen α3
Complement + neutrophils in glomeruli and alveoli
Hemoptysis + RPGN · linear IgG on IF
Acute rheumatic fever
II · cardiac myosin (mimicry with M protein)
Cross-reacting antibodies after GAS pharyngitis
Aschoff bodies, mitral damage
Pemphigus vulgaris · bullous pemphigoid
II · desmoglein 1/3 · hemidesmosome (BP180/230)
Acantholysis (intraepidermal) · subepidermal split
Flaccid bullae, ⁺ Nikolsky, mucosa · tense bullae, elderly
Graves disease · myasthenia gravis
II · TSH receptor · ACh receptor
Stimulating · blocking antibodies (no cell damage)
Transient neonatal disease from maternal IgG
Pernicious anemia
II · parietal cells / intrinsic factor
Loss of IF → B12 deficiency
Atrophic gastritis of body/fundus
Systemic lupus erythematosus
III · nuclear antigens (DNA, histones)
Immune complexes in skin, joints, kidney, serosa
↓ C3/C4 in flares · also type II cytopenias
Post-streptococcal GN
III · streptococcal antigens
Subepithelial humps, complement consumption
Cola urine 2–3 weeks after infection · ↓ C3
Polyarteritis nodosa · cryoglobulinemia
III · HBV antigens · HCV-related IgM-IgG
Vessel-wall complexes
PAN spares lungs · palpable purpura, low C4
Serum sickness
III · foreign proteins (antivenom, rituximab, infliximab) or drugs (penicillin, cefaclor, TMP-SMX)
Antibodies form after ~1–2 weeks; complexes deposit
Fever, urticarial rash, arthralgia, lymphadenopathy, proteinuria, ↓ C3
Arthus reaction
III · local antigen (tetanus/diphtheria booster) with high preexisting IgG
Complexes in dermal vessels → local vasculitis, necrosis
Hours after injection

Mechanism — type II vs type III

Type IIAntibody on a fixed cell or matrix
→
Damage where the antigen isLinear IF
Type IIIAntibody + soluble antigen in blood
→
Complexes deposit in vessels, glomeruli, joints
→
Complement → neutrophils → vasculitisGranular IF, ↓ C3

Type II subtypes

MECHANISM
EXAMPLES
RESULT
Cell destruction
AIHA, ITP, HDFN, transfusion
Lysis, phagocytosis
Inflammation
Goodpasture, rheumatic fever, pemphigus
Tissue injury
Receptor dysfunction
Graves, myasthenia, pernicious anemia
Altered function, no injury

How it's tested

COMMON CONFUSIONLinear IgG on GBM (Goodpasture, type II) vs granular "lumpy-bumpy" deposits (lupus nephritis, PSGN, type III).
THE TRAPSerum sickness appears 1–2 weeks after the drug or antiserum — the delay is the time to make antibodies.
YOUR APPROACHIs the antigen fixed (type II) or soluble (type III)? → mechanism → IF pattern and complement level → disease.

If you see… think…

Positive direct Coombs test → type II (antibody on RBCs)
Hemoptysis + RPGN with linear IgG → Goodpasture
Antibodies that stimulate the TSH receptor → Graves (type II, no damage)
Ptosis that worsens through the day, anti-AChR → myasthenia gravis
Flaccid bullae, oral erosions, anti-desmoglein → pemphigus vulgaris
Fever, rash, arthralgia 10 days after antivenom → serum sickness
Swollen, necrotic area hours after a tetanus booster → Arthus reaction
Granular IgG + C3 in glomeruli, low C3 → immune-complex GN
Rh ⁻ mother after delivery of Rh ⁺ baby → anti-D immune globulin
Polyarteritis nodosa association → hepatitis B