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Posts Tagged ‘immune system’

White blood cell chasing bacteria

Editor’s note: this is the 500th ThinkGene.com post, hurray!

It’s amazing how the cells look like conscious organisms chasing one another. Organisms on any level that are effectively predator and prey behave the same, be they single cells, insects, or animals.

Control switches found for immune cells that fight cancer, viral infection

Josh: If we can learn how to selectively disable/enable these specific points on HS1, then it would really help in cancer treatment. However, a lot of precautions have to be taken; incorrectly “programming” HS1 could lead to the NK (natural killer) cells attacking the body and doing more harm than good.

Medical science may be a significant step closer to climbing into the driver’s seat of an important class of immune cells, researchers at Washington University School of Medicine in St. Louis report in Nature Immunology.

The researchers showed that a single protein, HS1, enables key functions of natural killer (NK) cells, which kill early cancers and fight off viral infections. The protein allows the NK cells to pursue their targets, latch on to them and configure the cellular machinery it uses to kill them. … Continue Reading »

Researchers hack final part of the immune system code

A group of researchers from the University of Copenhagen and the Biocentre at the Technical University of Denmark have managed to decipher the final part of the immune system’s key codes.

The same researchers already broke the first part of the codes last autumn, and have now put together a comprehensive picture of how the immune system checks for dangers both in and outside our cells.

According to the researchers this new information, produced with the aid of artificial neural networks, means that it should be possible to predict all the immune system’s known, and also as yet unknown codes. This should in turn lead to the development of new targeted treatments, for e.g. cancer and infectious diseases.

Professor Søren Buus from the Faculty of Health Sciences at the University of Copenhagen has been at the forefront of this research project.

The body’s natural defences uses these key codes in such a way that microorganisms cannot spy on and discover its functions. It this unique protection that has so far made it difficult for scientists to decode the entire human immune system and thus develop precise immunological tools and carry out organ transplants.

Source: University of Copenhagen

Immune molecule that plays a powerful role in avoiding organ rejection identified

When a mouse’s immune system is deciding whether to reject a skin graft, one powerful member of a molecular family designed to provoke such a response can effectively reduce the visibility of the mouse’s own cells and help the graft survive, researchers say.

“This is a molecule with huge potential to regulate immune response,” Dr. Anatolij Horuzsko, reproductive immunologist at the Medical College of Georgia Center for Molecular Chaperone/Radiobiology and Cancer Virology, says of HLA-G dimer.

Dimer appears to be the most powerful among several known forms of HLA-G at inhibiting the immune response, researchers have found. Fetuses use this natural mechanism to hide from the mother’s immune system and it’s at work in some transplant patients as well.

Now that the scientists know which HLA-G is best at down-regulating the immune response and how it works, they believe the molecule’s action can be augmented in people with organ transplants and autoimmune disease and turned down to help fight a tumor. Measuring endogenous levels of HLA-G dimer may also help physicians identify which transplant patients require little, if any, immune suppression.

Research published online in Proceedings of the National Academy of Sciences details that when HLA-G dimer binds with its inhibitory receptor, ILT4, it triggers a signaling pathway in which immune molecules IL-6 and STAT3 play a major role. “Biologically this is an interaction that requires several important suppressive molecules,” says Dr. Horuzsko, the study’s corresponding author and a faculty member in the MCG Schools of Medicine and Graduate Studies.

They looked at the resulting strong signaling in culture, then measured its impact on skin graft survival in mice and found it prolonged survival. Now Dr. Horuzsko is working with Dr. Laura Mulloy, chief of the Section of Nephrology, Hypertension and Transplantation Medicine in the MCG School of Medicine, to see if this dimer form is at work in kidney transplant patients who avoid rejection.

HLA-G dimer’s target is another MHC molecule, which is essentially an individual’s unique tissue signature; HLA-G itself is a type of MHC. In fact, HLA – human leukocyte antigen – matching is done for organ and bone marrow transplants to try minimize the recipient’s reaction to the new organ. Transplant patients also take drugs that broadly dampen the immune response but can leave them more vulnerable to infections and disease.

Dr. Horuzsko notes that HLA-G can work through other cells, not just MHC molecules, and that not every HLA-G form is good at down-regulating MHC.

He plans to look at HLA-G dimer levels in tumor patients as well. “Tumors already down- regulate MHC molecules,” he says, referencing how tumors turn down their tissue expression so they can fly below the radar of the immune system. “We need to see what form of HLA-G cancers – including leukemia, lymphoma, melanoma and breast cancer – use and see their level of expression.” He notes that HLA-G isn’t the only mechanism cancers use to escape the immune response but that being able to control a tumor’s use of this molecule could offer a new way to target tumors for natural destruction.

A recent grant from the National Multiple Sclerosis Society is enabling studies of whether down-regulating MHC expression in multiple sclerosis patients can slow or arrest the immune system’s attack of the nerve’s protective covering. “The expression of the MHC molecule for some reason goes up – an infection might trigger the recognition of your own tissue – and the immune system attacks,” says Dr. Horuzsko. “We can generate a mouse with MS-like disease and target the HLA-G inhibitory receptor to see if it effectively down-regulates the disease.” He’ll look to see which, if any, of the HLA-G forms are most powerful in this autoimmune scenario.

Source: Medical College of Georgia

Siyuan Liang, Vladimir Ristich, Hisashi Arase, Jean Dausset, Edgardo D. Carosella, and Anatolij Horuzsko. Modulation of dendritic cell differentiation by HLA-G and ILT4 requires the IL-6—STAT3 signaling pathway. PNAS published June 11, 2008, 10.1073/pnas.0803341105 (Immunology).

Josh says:

I’ve always found immunology fascinating, and at one point was considering going into the field. This press release is a little on the technical side, as I’m not familiar with many of the molecules other than MHC (Major Histocompatibility Complex), which basically allows an organism to recognize itself from that which is foreign.

“Vaccine” for leukemia

Biology News reports that a research team at the Moores Cancer Center at University of California, San Diego (UCSD) have gotten a leukemia patient’s immune system to start attacking their leukemia cancer cells. To do this, the researchers modified cancer cells to make them more recognizable by the immune system. These immunity-recognizable cancer cells were then injected back into the patient so that their body could begin producing antibodies.

Basically: a vaccine for leukemia.

This works because the antibodies that are produced target a transmembrane receptor called ROR1, which is involved in the Wnt pathway. Normally our bodies destroy all immune cells that make antibodies that recognize self, which is anything that is naturally present in the body. However, this particular part of the Wnt pathway is only present early on in development, so all the ROR1 receptors are gone before the immune system develops.