How do immune cells detect infections?
鈥淔or immune cells, singling out foreign proteins is like looking for a needle in a haystack 鈥� where the needle may look very much like a straw, and where some straws may also look very much like a needle,鈥� notes 平特五不中 physics professor Paul Fran莽ois.
Understanding how immune cells tackle this formidable challenge is important, because it could provide crucial insights into the understanding of immune diseases, from AIDS to auto-immune disorders.
In a study published May 21 in the journal Physical Review Lettters, Fran莽ois and 平特五不中 graduate student Jean-Beno卯t Lalanne used computational tools to examine what kind of solutions immune systems may use to detect small concentrations of foreign antigens (characteristic of potentially harmful infections) in a sea of 鈥渟elf-antigens鈥� normally present at the surface of cells.
The researchers鈥� computer simulations yielded a surprisingly simple solution related to the well-known phenomenon of biochemical adaptation 鈥� a general biochemical mechanism that enables organisms to cope with varying environmental conditions.
To find solutions, the computer uses an algorithm inspired by Darwinian evolution. This algorithm, designed previously within the Fran莽ois research group, randomly generates mathematical models of biochemical networks. It then scores them by comparing properties of these networks to predefined properties of the immune system. Networks with best scores are duplicated in the next generation and mutated, and the process is iterated over many simulated 鈥済enerations鈥� until networks reach a perfect score.
In this case, almost all solutions found were very similar, sharing a common core structure or motif.
鈥淥ur approach provides a simpler theoretical framework and understanding of what happens鈥� as immune cells sort through the 鈥渉aystack鈥� to detect foreign antigens and trigger the immune response, Fran莽ois says. 鈥淥ur model shares many similarities with real immune networks. Strikingly, the simplest evolved solution we found has both similar characteristics and some of the blind spots of real immune cells we studied in a previous collaborative study with the groups of Gr茅goire Altan-Bonnet (Memorial Sloane Kettering, New York), Eric Siggia (Rockefeller University, New York) and Massimo Vergassola (Pasteur Institute, Paris).鈥�
Funding for the research was provided by the Natural Sciences and Engineering Research Council of Canada and the Human Frontier Science Program.
To access the abstract of the paper:聽
