Pathology · Advanced Pathology Mechanisms (Multi-topic)

Activation of the NLRP3 inflammasome in macrophages exposed to urate crystals leads to a form of regulated cell death characterised by membrane rupture and release of IL-1beta and IL-18. This death pathway is executed by:

  • A Gasdermin D pores formed after caspase-1 cleaves its N-terminal inhibitory domain
  • B MLKL oligomerising in the plasma membrane after RIPK3 phosphorylation
  • C Perforin-granzyme B entry through complement membrane attack complex pores
  • D Mitochondrial outer membrane permeabilisation by Bax and Bak oligomers
Correct answer: A. Gasdermin D pores formed after caspase-1 cleaves its N-terminal inhibitory domain

Explanation

Pyroptosis is executed by gasdermin D. Inflammasome-activated caspase-1 cleaves gasdermin D, releasing an N-terminal fragment that oligomerises into plasma membrane pores, causing osmotic lysis and secretion of mature IL-1beta and IL-18. Option B describes necroptosis, which is TNF-driven and independent of caspase-1. Perforin kills target cells via granzymes, and mitochondrial permeabilisation is the hallmark of apoptosis, which does not release inflammatory cytokines.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.

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