Overview

Granzymes are a group of proteolytic enzymes found in the secretory granules of cytotoxic lymphocytes. They are best known for helping the immune system eliminate virus-infected or malignant cells. Granzymes are produced and released by immune cells such as cytotoxic T cells and natural killer (NK) cells and often act together with other granule components to induce target-cell death. They belong to the family of serine proteases.

Structure and mechanism

Stored in granules alongside perforin and the proteoglycan serglycin, granzymes are activated on release. Perforin facilitates entry of granzymes into the target cell cytosol, where granzymes cleave specific substrates to trigger apoptotic or other death pathways. Different family members—commonly called granzyme A, granzyme B, granzyme K and others—have distinct substrate preferences and biochemical effects.

Biological roles and examples

Granzymes play central roles in antiviral defense, tumor immunosurveillance, and the clearance of damaged cells. For example, granzyme B cleaves and activates caspases and pro-apoptotic proteins, promoting classical apoptosis, while granzyme A can provoke caspase-independent DNA damage and inflammation. Outside direct cytotoxicity, extracellular granzymes can influence inflammation and tissue remodeling.

Detection and clinical relevance

Laboratory methods can measure granzyme release or presence to assess immune activity. Common assays include ELISPOT and ELISA formats and flow-based techniques; specific protocols and reagents vary by granzyme type. Research and clinical studies use these assays to monitor responses to infection, vaccination, or immunotherapy. See assay references: ELISPOT, secretion assays.

Notable distinctions and historical notes

  • Variety: multiple granzymes differ in targets and outcomes.
  • Entry: perforin-dependent delivery is the most common route.
  • Discovery: granzymes were characterized as key cytotoxic components in the late 20th century and remain active research topics.

For deeper background and protocols consult resources on lymphocyte cytotoxic mechanisms and assay methods: granule contents, viral immunity, target-cell interaction, and reviews of granzyme biology at specialist sources: enzyme families, NK cell function.