Granzymes are a family of enzymes, specifically proteases, that act as molecular tools within the immune system. These specialized proteins function like tiny cellular scissors, designed to break down other proteins. Their primary role involves initiating a controlled destruction process in target cells, helping to manage cellular threats as part of the body’s defense mechanisms.
The Cellular Origin of Granzymes
Granzymes originate primarily from two specialized types of immune cells: Natural Killer (NK) cells and Cytotoxic T Lymphocytes (CTLs), also known as CD8+ T cells. These cells serve as the immune system’s dedicated search-and-destroy units, constantly patrolling the body for abnormal or infected cells.
Before deployment, granzymes are carefully stored inside these immune cells within small, membrane-bound sacs called granules. These granules keep the powerful enzymes safely contained, preventing them from damaging the host cell that produces them. When an NK cell or CTL identifies a target cell, these granules move towards the point of contact, ready to release their contents.
The Mechanism of Cell Destruction
The controlled destruction of target cells by granzymes involves a precise partnership with another protein called perforin. When an immune cell encounters an infected or abnormal target cell, it forms a close connection known as an immunological synapse. Perforin is then released from the immune cell’s granules into this space.
Perforin creates pores in the target cell’s membrane, acting like a cellular punch. These pores allow granzymes to enter the target cell. Once inside, granzymes activate apoptosis, or programmed cell death. Granzyme B, for example, triggers apoptosis by activating caspases, which systematically dismantle the cell from within. Granzyme A can induce a different form of cell death by damaging the target cell’s DNA.
Granzymes in Immunity and Health
Granzymes safeguard the body against internal threats. One function is eliminating virus-infected cells. By destroying these cells, granzymes prevent viral replication and spread, limiting infection and serving as a fundamental antiviral defense.
Granzymes also contribute to the body’s continuous immune surveillance against cancerous or precancerous cells. Immune cells constantly scan for cells that have undergone abnormal changes and possess the potential to become tumors. Upon detection, granzymes initiate the destruction of these aberrant cells, preventing tumor development and progression.
The Role of Granzymes in Disease
While granzymes are beneficial, their unregulated or misdirected activity can contribute to disease. Overactivity or inappropriate release can damage healthy tissues. This misdirected activity is observed in autoimmune diseases, where the immune system mistakenly attacks the body’s own cells.
For instance, granzymes have been implicated in conditions such as rheumatoid arthritis, where they contribute to inflammation and tissue damage in joints. Granzyme K, in particular, has been identified as a factor that can activate the complement system, a part of the immune response that can cause inflammation and tissue destruction when dysregulated. Their presence in inflamed tissues in patients with various chronic inflammatory diseases suggests a role in sustaining pathology. Granzymes can also degrade components of the extracellular matrix, further contributing to tissue injury in such conditions.