Granzymes

Definition

Granzymes are serine proteases that are released by cytotoxic T lymphocytes and natural killer (NK) cells to induce apoptosis, or programmed cell death, in target cells. These enzymes play a critical role in the immune response by effectively eliminating infected or cancerous cells, thereby maintaining the integrity of the organism. Their mechanism involves entering target cells through perforin-formed pores, leading to a cascade of events that ultimately trigger cell death.

5 Must Know Facts For Your Next Test

1. Granzymes are classified into different types, with granzyme A and granzyme B being the most studied due to their significant roles in mediating apoptosis in target cells.
2. These enzymes can cleave various substrates within the target cell, leading to activation of caspases, which are key enzymes in the apoptotic pathway.
3. Granzymes can also exhibit pro-inflammatory effects and influence immune responses beyond just killing target cells.
4. Dysfunction or dysregulation of granzyme activity has been associated with various diseases, including autoimmune disorders and cancer progression.
5. Granzymes can also enter non-target cells under certain conditions, contributing to collateral damage during immune responses.

Review Questions

• How do granzymes function in the immune response to eliminate infected or cancerous cells?
  • Granzymes function by being released from cytotoxic T lymphocytes and NK cells upon recognizing infected or cancerous cells. They enter these target cells through pores formed by perforin. Once inside, granzymes activate caspases and other cellular pathways that lead to apoptosis, effectively killing the compromised cells and preventing further infection or tumor growth.
• Discuss the potential consequences of dysregulated granzyme activity in the context of immune diseases.
  • Dysregulated granzyme activity can lead to either excessive or insufficient apoptosis. In autoimmune disorders, overactive granzymes may cause healthy tissues to be targeted for destruction, leading to tissue damage and chronic inflammation. Conversely, in certain cancers, reduced granzyme activity can allow tumor cells to evade immune detection and destruction, promoting tumor survival and growth.
• Evaluate the role of granzymes in shaping both adaptive immunity and potential therapeutic strategies against tumors.
  • Granzymes play a pivotal role in adaptive immunity by ensuring that infected or cancerous cells are efficiently eliminated. Their ability to induce apoptosis provides a mechanism for maintaining tissue homeostasis while preventing the spread of infections. Understanding granzymes' functions has led to therapeutic strategies aimed at enhancing their activity against tumors or modifying their action to minimize damage in autoimmune conditions. This dual perspective on granzymes highlights their importance not only as immune effectors but also as potential targets for immunotherapy.

Related terms

Perforin: A pore-forming protein released by cytotoxic T cells and NK cells that facilitates the entry of granzymes into target cells.

Cytotoxic T lymphocytes (CTLs): A subtype of T cells that directly kill infected or cancerous cells, utilizing granzymes and perforin as part of their effector functions.

Apoptosis: A form of programmed cell death that is vital for development and homeostasis, characterized by specific cellular changes and elimination without triggering inflammation.