Granzymes

Definition

Granzymes are a family of serine proteases found in the cytotoxic granules of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). They play a crucial role in the adaptive immune response by inducing apoptosis, or programmed cell death, in target cells that are infected or cancerous.

5 Must Know Facts For Your Next Test

1. Granzymes trigger apoptosis in target cells through the activation of caspase enzymes, which dismantle the cell from within.
2. There are several different types of granzymes (e.g., granzyme A, B, H, K, and M) that can induce cell death through distinct pathways.
3. Granzymes work in conjunction with the pore-forming protein perforin, which creates holes in the target cell membrane to allow the entry of granzymes.
4. The expression and release of granzymes are tightly regulated to prevent damage to healthy cells and ensure the specificity of the cytotoxic immune response.
5. Dysregulation of granzyme-mediated cell death has been implicated in various autoimmune disorders and chronic inflammatory conditions.

Review Questions

• Explain the role of granzymes in the cytotoxic activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs).
  • Granzymes are serine proteases found in the cytotoxic granules of NK cells and CTLs. These cells release granzymes, along with the pore-forming protein perforin, to induce apoptosis in target cells that are infected or cancerous. Granzymes trigger a cascade of caspase enzyme activation, leading to the systematic dismantling of the target cell from within. The coordinated action of granzymes and perforin is a key mechanism by which cytotoxic lymphocytes eliminate threats to the body's health and integrity.
• Describe the different types of granzymes and their distinct pathways for inducing cell death.
  • There are several different types of granzymes, including granzyme A, B, H, K, and M, each with its own unique mechanisms for triggering apoptosis. For example, granzyme B directly activates caspase enzymes, while granzyme A induces cell death through a caspase-independent pathway involving the cleavage of specific cellular substrates. The diversity of granzyme subtypes allows cytotoxic lymphocytes to target and eliminate infected or cancerous cells through multiple, complementary pathways, ensuring a robust and effective immune response.
• Discuss the importance of the regulation of granzyme expression and release in maintaining the specificity and safety of the cytotoxic immune response.
  • The expression and release of granzymes are tightly regulated to prevent damage to healthy cells and ensure the specificity of the cytotoxic immune response. Granzymes are stored in cytotoxic granules within NK cells and CTLs, and their release is carefully controlled to only occur when the lymphocyte recognizes a target cell as infected or cancerous. Dysregulation of granzyme-mediated cell death has been implicated in various autoimmune disorders and chronic inflammatory conditions, highlighting the critical role of this regulatory mechanism in maintaining immune homeostasis and preventing self-harm. The precise regulation of granzyme activity is, therefore, essential for the adaptive immune system to effectively eliminate threats while preserving the integrity of the host.

Related terms

Cytotoxic T Lymphocytes (CTLs):

A type of T cell that can directly kill virus-infected or cancerous cells through the release of cytotoxic granules containing granzymes and perforin.

Natural Killer (NK) Cells:

A type of lymphocyte that can directly kill virus-infected, stressed, or cancerous cells through the release of cytotoxic granules containing granzymes and perforin.

Apoptosis:

A form of programmed cell death that occurs in multicellular organisms, characterized by specific morphological and biochemical changes, including the activation of granzymes.