New device detects signal from immune system cellSeptember 4th, 2008 - 2:20 pm ICT by IANS
Washington, Sep 4 (IANS) Scientists have detected for the first time chemical signals that single cells in the immune system use to communicate with one another over short distances.The signals were found to originate in dendritic cells - sentinels of the immune system that detect microscopic invaders at the outset - and were received by nearby T-cells, which play crucial roles in the immune system, including coordination of attacks on invading agents.
The chemical signals that cells exchange have been studied extensively. But it has not been possible to detect chemical messages travelling between cells that are close but not in contact - called paracrine signals - because they are highly localised and they are produced in concentrations below detection levels.
A new technology, called a multi-trap nanophysiometer (MTN), was required to demonstrate the existence of non-contact signalling. This is one of the first microfluidic devices that has been applied successfully to the study of cell-to-cell signalling in the immune system.
The MTN was developed by a team of researchers at the Vanderbilt Institute for Integrative Biosystems Research and Education headed by John P. Wikswo, Gordon A. Cain University professor at Vanderbilt.
“This is an important advance and potentially very useful technology,” said study co-author Derya Unutmaz, now an associate professor of microbiology at New York University’s School of Medicine.
“The ability to study the behaviour of single cells may not be as critical if you are studying the heart or muscles, which are mostly formed by uniform cells, but it is crucial for understanding how the immune system functions.
“The wide surveillance of the body that it conducts requires extensive communication between dozens of different kinds of immune cells,” Unutmaz said.
The reason for this is that the dendritic cells, T-cells and B-cells in the immune system, which tend to concentrate in the lymph nodes spread throughout the body, function as individual, unattached cells.
If dendritic cells detect invaders in the body, they rapidly migrate to lymph nodes and have to find the appropriate T-cells to alert them. But how dendritic cells attract the right T-cells among millions of cells within the lymph nodes remains an immunological puzzle.
Scientists have been trying to develop systems for single-cell analysis for a number of years. Because of the difficulty of keeping normal cells alive, they have been forced to use cells that have been genetically altered so they can be cultured indefinitely.
Although the alteration “immortalises” the cells, it also significantly limits their usefulness. The MTN is the first system that can monitor biochemical changes in large numbers of normal or primary cells at the single-cell level for prolonged periods, Unutmaz says.
Researchers monitor the cells with a digital camera attached to a standard microscope, typically snapping images every 30 seconds.
They have written software that allows them to analyse the movements and reactions of individual cells. They can record various cell behaviours by injecting different fluorescent dyes into the cells.
The surprise discovery of paracrine signalling was made by graduate student Shannon Faley, now a postdoctoral research associate at the University of Glasgow, Scotland.
These findings appeared online in Lab on a Chip journal.