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Related Experiment Videos

The granule pathway of programmed cell death.

Philip G Ashton-Rickardt1

  • 1The University of Chicago, Department of Pathology and Ben May Institute for Cancer Research, 924 E. 57th Street, Chicago, IL 60637, USA.

Critical Reviews in Immunology
|July 29, 2005
PubMed
Summary

Cytotoxic lymphocytes use granzymes and perforin to kill cells, but can also damage themselves. They possess protective mechanisms, like serine protease inhibitors, to prevent self-inflicted harm from granzyme B.

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Cytotoxic lymphocytes eliminate infected or transformed cells via exocytosis of granzymes.
  • Perforin facilitates granzyme entry, initiating apoptosis through substrate cleavage.
  • Granzymes induce cell death via mitochondrial dysfunction and DNA/nuclear damage.

Purpose of the Study:

  • To explore the self-damaging potential of cytotoxic lymphocytes.
  • To investigate mechanisms protecting cytotoxic lymphocytes from granzyme-mediated damage.
  • To understand how pathogens and tumors evade granzyme-induced cell death.

Main Methods:

  • Review of existing literature on granzyme function and lymphocyte protection.
  • Analysis of studies involving perforin and granzyme-deficient mice and humans.

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  • Examination of proposed endogenous protective mechanisms.

    • Main Results:

    • Cytotoxic lymphocytes are vulnerable to self-inflicted damage from their own granzymes.
    • Deficiencies in perforin and granzymes suggest a role in regulating immune responses.
    • Endogenous serine protease inhibitors are implicated in protecting lymphocytes from granzyme B.
    • Viruses and tumors may exploit these protective pathways to evade immune attack.

    Conclusions:

    • Cytotoxic lymphocytes have evolved self-protection mechanisms against granzyme-induced damage.
    • Understanding these mechanisms is crucial for both immune regulation and therapeutic strategies against cancer and infections.