Emory scientists track down immune sentinel cells with gene gun

August 29, 2003

ATLANTA--Dendritic cells monitor foreign substances in the body and communicate whether they present a danger to the rest of the immune system. Emory immunologists have developed a sensitive method to detect and follow dendritic cells by marking them with a change in their DNA, and have discovered that they are more numerous and longer lived than other scientists had previously observed. Their research uses a gene gun, which shoots DNA into the skin using microscopic gold pellets, and could lead to a faster and simpler way to vaccinate against emerging diseases like West Nile virus, SARS, or hepatitis C.

The research was published online August 10, and will appear in the journal Nature Immunology in September. Lead authors are Sanjay Garg PhD, postdoctoral fellow, and Joshy Jacob, PhD assistant professor of microbiology and immunology at Emory University School of Medicine and the Yerkes National Primate Research Center. Both are members of the Emory Vaccine Center.

Dendritic cells, the security cameras of the immune system, derive their name from their finger-like projections. They continually capture external proteins, digest the proteins into fragments, and display those fragments on their surfaces. T cells, the police who watch the cameras, have the ability to examine the fragments on the dendritic cells' surfaces and sound the alarm to the rest of the immune system if they determine that those fragments are dangerous. Although other kinds of cells also have the ability to present fragments of foreign proteins to the immune system, dendritic cells are the most proficient, and immunologists call them "professional" antigen-presenting cells.

Dendritic cells migrate between the skin, where one might expect to first encounter an intruder, and the lymph nodes, where T cells and other white blood cells congregate. Dr. Jacob's group used transgenic mice engineered with a marker gene that can be easily detected by staining, but only when that gene is rearranged by an external signal. They shot the trigger signal - DNA encoding a specialized bacterial enzyme - into the skin of the mice. All the cells in the skin received the trigger signal, but only the dendritic cells migrated to the draining lymph nodes.

Dr. Jacob estimates that there are 1,000 dendritic cells for every square millimeter of skin. His group found that the number of dendritic cells that migrate into the lymph nodes is 100 times higher than previously thought, and that they live for two weeks, rather than just a few days. The scientists were able to observe the dendritic cells more accurately because the cells were marked permanently.

"This research resolves a long-standing puzzle," says Dr. Jacob. "T cells that will recognize a given foreign protein are quite rare, so it was hard to imagine how the T cells and dendritic cells would ever meet. It is still remarkable that they do."

The gene gun used to send the DNA into the skin uses gold pellets coated with the DNA. The pellets have a diameter of one micrometer and are driven with the force of a bullet. Dr. Jacob suggests that the DNA provides just enough of a signal to induce the dendritic cells, which are activated by inflammation or physical trauma, then migrate to the lymph nodes.

The gene gun could present an attractive alternative to conventional ways of making vaccines, Dr. Jacob notes. "Usually, you have to figure out how to grow a virus, then inactivate it so that it doesn't actually cause an infection. This new methodology could take advantage of the immunizing capabilities of abundant, long-lived dendritic cells."
-end-


Emory University Health Sciences Center

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.