Cell injury: necroptosis: practice question

A Pathology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pathology · Cell injury: necroptosis

Sample item

In cultured hepatocytes infected with a virus that expresses a caspase-8 inhibitor, TNF still causes cell death with swelling, membrane rupture and release of inflammatory contents. No caspase activation is detected. Which mediators drive this death?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. RIPK1, RIPK3 and the pseudokinase MLKL

When caspase-8 is blocked, TNF receptor signalling shifts from apoptosis to necroptosis, a regulated form of necrosis. RIPK1 and RIPK3 phosphorylate MLKL, which oligomerises and ruptures the plasma membrane, so inflammatory contents leak out. It looks morphologically like necrosis but is genetically programmed and caspase independent.

Option by option

  • A. Apaf-1 and caspase-9 forming an apoptosome after cytochrome c release

    The apoptosome is the intrinsic apoptotic pathway and requires caspase-9 activation, which was excluded.

  • B. RIPK1, RIPK3 and the pseudokinase MLKL (correct)

    Correct. The RIPK1, RIPK3 and MLKL axis defines necroptosis.

  • C. NLRP3 inflammasome activation of caspase-1 with release of IL-1 beta

    Caspase-1 activation is pyroptosis, which is a caspase-dependent death triggered by inflammasomes, not by TNF with blocked caspase-8.

  • D. Granzyme B delivered through perforin pores of cytotoxic T cells

    Granzyme B triggers apoptosis through caspases and acts on targets of cytotoxic lymphocytes, not on TNF-stimulated hepatocytes.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

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Questions about this Pathology question

What is the answer to this Pathology question?

The best answer is B, RIPK1, RIPK3 and the pseudokinase MLKL. When caspase-8 is blocked, TNF receptor signalling shifts from apoptosis to necroptosis, a regulated form of necrosis.

Why is "Apaf-1 and caspase-9 forming an apoptosome after cytochrome c release" not the answer?

The apoptosome is the intrinsic apoptotic pathway and requires caspase-9 activation, which was excluded.

Why is "NLRP3 inflammasome activation of caspase-1 with release of IL-1 beta" not the answer?

Caspase-1 activation is pyroptosis, which is a caspase-dependent death triggered by inflammasomes, not by TNF with blocked caspase-8.

Why is "Granzyme B delivered through perforin pores of cytotoxic T cells" not the answer?

Granzyme B triggers apoptosis through caspases and acts on targets of cytotoxic lymphocytes, not on TNF-stimulated hepatocytes.

What concept does this question test?

It tests Cell injury: necroptosis in Pathology. RIPK1 and RIPK3 phosphorylate MLKL, which oligomerises and ruptures the plasma membrane, so inflammatory contents leak out. It looks morphologically like necrosis but is genetically programmed and caspase independent.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Cell injury: necroptosis?

Learn each disease as a bundle: cause, key histology, markers, and the clinical hallmark. Then use the flashcards and the other Pathology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.