Related Experiment Video
Updated: Jul 19, 2026
05:20
A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
Granzyme B and natural killer (NK) cell death
Hiroaki Ida1, Paul J Utz, Paul Anderson
1First Department of Internal Medicine, Graduate School of Biochemical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan. idah@net.nagasaki-u.ac.jp
Modern Rheumatology
|October 10, 2006
Summary
Granzyme B, a serine protease, induces target cell death and is implicated in autoimmune diseases. Its leakage from natural killer (NK) cells triggers apoptosis, contributing to cell death in conditions like rheumatoid arthritis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Medicine
Background:
- Granzyme B is a serine protease vital for inducing target cell death.
- Mechanisms of granzyme B delivery to target cells and its role in autoimmunity are under investigation.
- Autoantibodies against granzyme B neoepitopes are found in autoimmune diseases, suggesting its involvement in disease progression or regulation.
Purpose of the Study:
- To explore the role of granzyme B in target cell death and autoimmunity.
- To investigate a novel mechanism of granzyme B-mediated cell death: granzyme B leakage-induced cell death.
- To discuss the influence of granzyme B on natural killer (NK) cell death.
Main Methods:
- Analysis of granzyme B's role in target cell death pathways.
- Identification and characterization of granzyme B leakage-induced cell death.
- Evaluation of granzyme B's interaction with its inhibitor, serpin proteinase inhibitor 9.
- Discussion of granzyme B's involvement in autoimmune diseases and NK cell apoptosis.
Main Results:
- Granzyme B directly activates Bid, leading to caspase activation and apoptosis.
- A novel mechanism, granzyme B leakage-induced cell death, was identified in activated NK cells.
- Leakage of granzyme B from NK cell granules into the cytoplasm triggers apoptosis by directing Bid to mitochondria.
- An imbalance between granzyme B and its inhibitor, serpin proteinase inhibitor 9, determines cell death.
Conclusions:
- Granzyme B plays a significant role in both target cell death and autoimmune processes.
- Granzyme B leakage from NK cells is a critical mechanism for inducing apoptosis, particularly when granzyme B levels exceed those of its inhibitor.
- Understanding granzyme B's function in autoimmunity and NK cell death offers insights into disease pathogenesis and potential therapeutic targets.
Related Concept Videos
01:28Cells of the Innate Immune Response
The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
01:25Immune Surveillance by NK Cells and Phagocytes
Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
01:27Cytotoxic T Cells-mediated Immune Response
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...