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Australian scientists find immune complications caused by drugs

Australian scientists find immune complications caused by drugs Science & Technology World Website

Australian researchers are a step closer to understanding immune complications caused by commonly prescribed medications.

Many well-known and commonly prescribed drugs that are successfully used to treat diseases can also have harmful side effects. While it has been known that some drugs can inhibit the immune system, why it occurs has remained a mystery.

Research published by Monash University and the University of Melbourne on Tuesday has taken the most significant step yet in understanding the process that inhibits the immune system.

The research team investigated Mucosal associated invariant T (MAIT) cells, a specialized type of immune cells, to discover what type of drugs were activating the MAIT cells.

They found that some drugs prevented the MAIT cells from performing their main function of detecting infections while others activated the immune system.

Andrew Keller, lead author of the study which was published in Nature Immunology, said the research should lead to a much better understanding of immune reactions by some people to certain drugs.

Keller said that the T cells were an integral part of the body's immune system.

"They protect the body by 'checking' other cells for signs of infection and activating the immune system when they detect an invader," Keller said in a statement.

"This arrangement is dependent on both the T cells knowing what they're looking for, and the other cells in the body giving them useful information."

Sidonia Eckle from the Peter Doherty Institute for Infection and Immunity at the University of Melbourne said the implications point to possible links between MAIT cells and drug hypersensitivities.

"A greater understanding of the interaction between MAIT cells and other host cells will hopefully allow us to better predict and avoid therapeutics that influence and cause harm," Eckle said.

"It also offers the tantalizing prospect of future therapies that manipulate MAIT cell behavior, for example, by enhancing or suppressing immune responses to achieve beneficial clinical outcome."

Researchers shed new light on skin-based immune system

Australian scientists find immune complications caused by drugs Science & Technology World Website

The skin is the body's first line of defense against infection, with an extensive network of skin-based immune cells responsible for detecting the presence of foreign invaders. However, in addition to pathogens, an immune response can be triggered by allergens or even our own cells, resulting in unwanted inflammation and allergies. Researchers have now shed new light on the way the immune system in our skin works, paving the way for future improvements in tackling infections, allergies and autoimmune diseases.

An international team, comprising scientists from Monash University and the University of Melbourne in Australia and Harvard University in the US, looked at how our skin’s immune cells make sense of foreign lipids (fat-like molecules derived from bacteria), as well as lipids from human cells.

Scientists have known for years that a molecule found in skin-based immune cells called CD1a played a role in immunity to mycobacteria (a genus of Actinobacteria that includes pathogens that cause serious diseases in mammals, such as tuberculosis) and bee stings, but were unsure exactly what that role was. It is this mystery the research team has solved.

Using x-ray crystallography, which can identify structures at the atomic and molecular level, they found how CD1a binds to lipids – be they from pathogens, allergens or our own cells – highlighting them for recognition by T lymphocytes (or T cells), a type of white blood cell that is an integral part of the immune system.

The scientists not only uncovered this hitherto unknown operation of how the immune system interacts with CD1a molecules, but have also begun to understand how this might be used to improve immunity from infection as well as suppress the kind of immunity that misfires and leads to allergic reaction.

"By understanding how the human immune system can sense and respond to lipids, we can make them more or less potent by subtly altering their structure," says Professor Jamie Rossjohn from Monash University.

However, the scientists stress that the research is still in its nascent stage at this point and direct applications will be some time coming.

Vaccine-style treatment for rheumatoid arthritis retrains the immune system

Australian scientists find immune complications caused by drugs Science & Technology World Website

According to the American College of Rheumatology, more than one million Americans suffer from rheumatoid arthritis. The disease gives rise to swelling and pain by causing the immune system to malfunction and attack healthy tissue. No cure is available, though aggressive and varied drug treatments can curb its effects. Now, success in an early clinical trial suggests that a new form of therapy could stop these symptoms taking hold by retraining the patient's immune system to ignore a peptide it normally identifies as a foreign foe.

Normally, our immune cells trawl through our blood and tissue, sorting foreign matter from healthy tissue to fight off signs of infection. Rheumatoid arthritis takes effect when these immune cells incorrectly identify healthy cells as foreign and attack them instead.

Rather than looking at ways to treat the effects once this chain of events has already played out, researchers from Australia's University of Queensland looked to zero in on the root cause. Led by Professor Ranjeny Thomas, the team developed a vaccine-style therapeutic approach, or immunotherapy, for people with the most common form of rheumatoid arthritis, known as CCP-positive.

The treatment is designed to re-educate the body's immune system to leave certain naturally occurring peptides alone, therefore preventing inflammation. To accomplish this, immune cells known as dendritic cells are extracted from the body and mixed with an anti-inflammatory drug and a natural peptide found in arthritic joints, before being injected back into the body once again.

"The dendritic cells are educators of the immune system," Thomas explains to Gizmag. "They show peptides to the immune system and the T lymphocytes (student soldiers) then get the message to either attack or do a peace-keeping mission for that peptide. When we deliver peptide and an anti-inflammatory drug to a dendritic cell, it teaches the T lymphocytes to keep the peace in that tissue, thus keeping it healthy."

In its current state, the treatment is too expensive and time-consuming to see it adopted for widespread use. But Thomas says the study's results, which indicate a single injection of the immune-modified dendritic cells can help suppress the effects of rheumatoid arthritis, are promising enough to continue development of more practical versions of the therapy, such as using nanoparticles as a delivery mechanism.

"We can use a nanoparticle to package the drug and the peptide," she says. "After injection, the nanoparticle finds the dendritic cells and delivers the payload to them in the body. So far this has been tested in animal models but we plan to test in RA (rheumatoid arthritis) patients in 2016."

If the approach is proven successful for sufferers of rheumatoid arthritis, it could potentially be used to treat other autoimmune diseases, such as Type 1 diabetes and and multiple sclerosis.

The research findings were published in the journal Science Translational Medicine.



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