During a dengue outbreak, serotype-2 (DENV-2) is identified. A patient who had dengue serotype-1 (DENV-1) three years ago now presents with dengue hemorrhagic fever (DHF). The immunopathological basis of increased severity on secondary infection is:

• A Primary DENV-1 infection depleted memory T cells, leaving the patient immunocompromised
• B DENV-2 is intrinsically more virulent than DENV-1 and always causes DHF regardless of prior immunity
• C Cross-reactive IgM from the first infection directly activates complement causing vascular damage
• D Antibody-dependent enhancement (ADE): cross-reactive non-neutralizing IgG from DENV-1 binds DENV-2, facilitating Fc-receptor-mediated entry into monocytes/macrophages, amplifying viral load and cytokine storm ✓

Explanation

The ADE hypothesis explains DHF/DSS in secondary heterotypic dengue infection. Non-neutralizing (sub-threshold) IgG antibodies from the primary infection cross-react with the new serotype and form immune complexes. Instead of neutralizing the virus, these complexes promote efficient Fc-γRII–mediated uptake into monocytes and macrophages — the primary replication sites — increasing viral load. Activated infected monocytes release massive amounts of TNF-α, IL-6, and IL-10, causing plasma leakage and hemorrhage.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.