A new study has unearthed the secret behind how our immune cells are able to kill infected or cancerous cells without killing themselves in the process.
The focus of the study is a molecule known as perforin, whose job it is to open up a pore in cells targeted for destruction. With that pore in place, proteases known as granzymes can enter target cells and destroy them.
Perforin is one of the most critical ingredients for a functional immune system. Without it, mice succumb to viral illness and lymphoma. Humans born without a working perforin gene develop an aggressive immunoregulatory disorder in the first few months of life and usually die unless treated with cytoxic drugs or a bone marrow transplant.
But perforin itself is an incredibly destructive molecule. "Perforin forms a massive pore," said Ilia Voskoboinik of the Peter MacCallum Cancer Centre in Australia. "It allows almost any protein to diffuse into a target cell. A few hundred molecules of perforin is sufficient to obliterate any cell."
When the immune cells known as cytotoxic lymphocytes (including cytotoxic T lymphocytes and natural killer cells) are activated, "they produce a massive amount of perforin, yet the cells are fine," Voskoboinik said.
The question was: how do our immune cells manage such toxic cargo without endangering themselves?
"Perforin goes from zero to extremely high levels within 24 hours and it has everything it needs to be functional," Voskoboinik said. "The cell relies on a really efficient transport system to move perforin away from the danger zone and as a result the cell is absolutely protected."
The findings "close a chapter" in our understanding of the immune system that has existed in the field since perforin was discovered almost 25 years ago, Voskoboinik said.
The study was recently published in Immunity, a Cell Press publication.