Tag Archives: immune system

Dead and dying metastatic prostate cancer cells (round light-colored area) inside a lymph node, surrounded by purple-stained lymphocytes of the immune system. Upper left and lower right corners: degenerating metastatic cells that still make prostate-specific antigen (PSA), which stains brown. (c) University of Minnesota

Going to the root of cancer fatality: metastasis

It’s not the cancer tumor itself that kills people, but rather the spread of cancer cells is what ultimately may bring the killing blow to patients. This is called metastasis, and oddly enough not nearly enough is known about how it works. University of Minnesota researchers have devised a pathological method for doctors to assess whether or not in lymph nodes the immune cells are winning against cancer or not. This may help predict outcomes for patients.

Metastasis is responsible for 90% death related to human solid-organ cancer. Many of the metastasizing cells  accumulate into what are called lymph nodes  – an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach and linked by lymphatic vessels. In these key locations, the immune system is on full on war with cancer cells, trying to seek out the cancer and destroy it. From the lymph glands, some cancer cells manage to escape through the bloodstream and sometimes can spread into other parts of the body. Doctors typically analyze lymph nodes thoroughly because they serve as a good indicator for metastasis concentration and staging cancer.

There are many things we don’t know yet about metastasis works, however. For instance, some lymph nodes may be positive or negative for cancer cells. Oddly enough, many patients diagnosed with positive lymph nodes (filled with cancer) out live those with negative lymph nodes. University of Minnesota prostate cancer researcher Akhouri Sinha and colleagues sought to understand why some patients with positive nodes survive a long time, while others die within a few years by looking deeper in nodes after cancer cells have metastasized there.

[RELATED] Cancer cells imaged in real time

After analyzing 32 cancer-positive pelvic lymph nodes from prostate cancer patients the researchers found that in some of these nodes the immune system was doing a pretty good job – it was winning the fight against cancer. In other nodes, however, the immune system was failing at killing cancer cells. So two types of nodes suddenly surface: one type where the immune system is more vulnerable to cancer, and the other where it’s less vulnerable.

Dead and dying metastatic prostate cancer cells (round light-colored area) inside a lymph node, surrounded by purple-stained lymphocytes of the immune system. Upper left and lower right corners: degenerating metastatic cells that still make prostate-specific antigen (PSA), which stains brown.  (c) University of Minnesota

Dead and dying metastatic prostate cancer cells (round light-colored area) inside a lymph node, surrounded by purple-stained lymphocytes of the immune system. Upper left and lower right corners: degenerating metastatic cells that still make prostate-specific antigen (PSA), which stains brown. (c) University of Minnesota

The researchers hypothesize that patients whose nodes show significant cancer cell death will do better than those whose nodes show little or none because that may signal the rise of cells resistant to attack by the immune system. These patients may require more aggressive therapy.  It’s important to note that his approach can be applied to breast, lung, pancreas, colon, and other solid organ cancers.

“Our paper shows that some populations of metastatic cells are [susceptible to immune attack], and others are not,” Dr. Sinha says. “This provides a potential explanation for the observation that some patients survive longer, even with metastatic disease.”

With this in mind, the researchers suggest that cancer patients asks their pathologists to analyze their lymph nodes, through a standard procedure, to see whether or not the immune system is winning against cancer cells. Next, the researchers plan on making a thorough correlation between the degree of cancer cell death in the nodes and patient survival rates. Also, the genetic markup of cancer cells in lymph nodes will be compared to those win the original tumor to see if this makes a vital difference in how cancer metastasizes.

Findings appeared in the journal Anticancer Research.

Researcher finds new immune system in mucus

Think about mucus – what comes to mind? It’s slimy, it’s gross, no one really likes it, right? Well, as a team from San Diego State University showed, mucus is also home to a very powerful immune system that has the possibility to change the way doctors treat a number of diseases.

Bacteriophages are basically viruses that infect and replicates within bacteria. The research addressed all sorts of animals, from sea anemones to mice and humans, and found that bacteriophages adhere to the mucus of all of them. They placed bacteriophage on top of a layer of mucus-producing tissue and observed that the bacteriophage formed bonds with sugars within the mucus, adhering to its surface every single time.

Print

They then challenged them by injecting E. Coli in the mucus, and they found that the bacteriophage attacked and killed off the E. coli in the mucus, effectively forming an anti-microbial barrier protecting the host from infection and disease.

In order to test their discovery, they then conducted parallel research on non-mucus producing cells, infecting them with E. Coli, in the same fashion. The results were disastrous for the cells.

“Taking previous research into consideration, we are able to propose the Bacteriophage Adherence to Mucus — or BAM — is a new model of immunity, which emphasizes the important role bacteriophage play in protecting the body from invading pathogens,” Barr said.

But what makes this finding really special is that that the bacteriophage are already present on all humans and animals; they are recruited almost as mercenaries by cells who support them and then act as protectors to the host, attacking invaders on their own.

“The research could be applied to any mucosal surface,” Barr said. “We envision BAM influencing the prevention and treatment of mucosal infections seen in the gut and lungs, having applications for phage therapy and even directly interacting with the human immune system.”

Research paper.

old-age

Women may live longer than men due to stronger immune system

old-age

The life expectancy gap between men and women is a rather attested fact, and while in the past a laborious, physically tense lifestyle for men was used to serve as an explanation, in our day and age of gender equality this doesn’t quite cut it anymore. Researchers in Japan might have stumbled across a clue that explains why women life longer then men, after they found that at old age women’s immune system is stronger than men’s.

In the United States, based on a 2005 census, the life expectancy gap between men and women is 5.3 years, with women expected to live on average up to 80.1 years. In Japan, a country which holds the record for life expectancy among the world’s populations, the gap is even wider with women being expected to live on average six years longer than men.

Many theories have been proposed in attempt to explain this gap. In fact, it turns out the females of most species live longer than males, which might mean that the life expectancy gap might be deeply rooted in our biology. A theory says women live longer men because they’re less ‘disposable’. Bear with me. The idea is that men’s reproductive role is less dependent on health than that of women, and as such the biological repairing mechanisms (DNA and cell division to replace old and dead cells) might be more refined in women. Other ideas state that male testosterone is actually harmful in the long run and may reduce life expectancy, although tangible evidence is insufficient to back this up.

Scientists at Tokyo Medical & Dental University have a different explanation, and their research has provided evidence to that shows women’s immune system at old age is stronger than in men. The findings were made after the researchers examined the blood of 356 men and women aged between 20 and 90 years old, looking to study key immune system signals – the levels of white blood cells and cytokines, which help to carry messages in the immune system.

As expected, in both sexes the number of white blood cells decreased with age, but two key elements – known as the T-cell and B-cell lymphocytes, declined faster in men. They also found that another type of cell that tackles viruses and tumours increased with age, with women having a higher rate of increase than men. Moreover,  two types of cytokines that help to keep the immune system under control and prevent inflammation from damaging surrounding tissue showed a decline only in men.

“It is well known that ageing is associated with a decline in the normal function of the immune system, leading to increased susceptibility to various diseases and shortened longevity,” said Professor Katsuiku Hirokawa.

“However, specific dysfunctions in the immune system directly responsible for this have yet to be identified.

“Among the important factors, T cells are central to the immune response, and their function is significantly altered with increasing age.”

Besides trying to explain the life expectancy gap, the findings also could serve a better indicator for calculating biological age, based on the state of one’s immune system.

 “Because people age at different rates, a person’s immunological parameters could be used to provide an indication of their true biological age,” Hirokawa said.

The findings were reported in the journal  Immunity and Ageing

Better looking specimens have healthier children, a study on great tits shows

Great tits are widespread species throughout Europe, the Middle East, Central and Northern Asia, and parts of North Africa in any sort of woodland. They tipically don’t migrate, except for very harsh winters. According to a new paper published in BioMed Central’s open access journal Frontiers in Zoology, the female’s appearance can be correlated with healthy attributes in offspring.

tits

The black stripe across her breast and white patches on her cheeks correlate to a chick’s weight at two weeks and immune strength respectively – thought the former can be in fact a genetic trait, while the latter can be an effect of nurture rather than nature.

However, researchers from Palacky University in the Czech Republic played a nasty trick on a pair of tits, swapping their offspring to test their theories. They investigated the growth and health of the infants and the ‘ornamentation’ of their mothers. The factors they took into consideration were weight, size and immune strength. What they found was that indeed, there is a correlation between the chick’s weight at two weeks and the size of black breast stripe on the genetic mother.

The body size of the chick is only related to its mother’s body size, and not its ornamentation, but strength of chick’s immune response was in fact connected to the white cheek patch. Talking about how the ornaments evolved to represent other bodily traits, Vladimír Remeš and Beata Matysioková who performed this study explained:

“Bigger healthier babies are important to the reproductive success of individuals, because they are more likely to survive to adulthood — so it is useful for birds to be able to work out which potential mates will produce the best babies. Maintaining bright colouration uses up resources which could otherwise be invested in reproduction or self-maintenance — consequently the evolution and maintenance of ornamentation in female great tits is probably due to direct selection by males.”

cytomegalovirus

Great leaps forward have been made in the fight against the biggest hidden virus

cytomegalovirus

A virus that most of us carry, yet which is remarkably obscure both to the immune system and the general public in terms of awareness, is responsible for a number of health hazards in the human body. In time, it tires the immune system which is forced to seek and fight it for a life time, exposing the body to other health hazards, and is the number one infectious cause of congenital birth defects. Researchers  at Cardiff University and the La Jolla Institute, California, have now made great strides forward in killing the virus after they identified the cellular mechanism it uses to infect its host body, thus providing key information that one day might allow an effective vaccine to be developed.

One child in 750 is born with a congenital defect like hearing or brain damage as a result of cytomegalovirus (CMV) infection – much more than other well-known congenital problems, such as Down’s syndrome or fetal alcohol syndrome. Despite this, few people are aware of its existence or of the fact they carry it.

What makes it so dangerous is its stealthy nature which makes it very difficult for the immune system to identify it. To top things over, the virus belongs to the herpes family of viruses that cause cold sores, chicken pox and other maladies, and like its brethren it never goes away. Also,  the constant struggle and stress the immune system is subjected to as it tries to control the virus tires and weakens it in the process, exposing it to other maladies.

“We have identified a novel trick that this virus uses to hide from immune detection,” says La Jolla Institute scientist Chris Benedict, Ph.D., a CMV expert. “By uncovering this mechanism, we’ve provided an important piece of the CMV puzzle that could enable vaccine counter strategies that flush out and eliminate virus-infected cells.”

A well hidden pest

What the researchers found was  that specific CMV gene (called UL141) blocks the ability of two key immune pathways to kill CMV-infected cells. These are TRAIL “death receptor” 1 and 2, first discovered some 15 years ago that normally work to kill infectious cells. The TRAIL death receptors have been the subject of study for oncologists for many years, interested in targeting them for anti-tumor therapies.

By identifying the UL141 gene as an inhibitor of TRAIL’s ability to carry out its killing function, the researchers hope this new found information will play a pivotal role in developing an effective vaccine against the CMV virus.

“This finding puts on the table the importance of TRAIL signaling in host (our body’s) defense and how the virus works to block these efforts,” says Ed Mocarski, Ph.D., a scientist at the Emory University School of Medicine’s Vaccine Center, whose research focuses on new ways to combat CMV. “This knowledge could set the stage for developing ways to boost the adaptive immune response which could ultimately aid in developing an effective vaccine.”

The findings were reported in the journal Cell Host & Microbe.

newborn-baby

Vaccine that works for newborns might save millions of babies

Babies need to wait until they’re at least two months old for vaccines to work, which leaves  a lot of newborn babies in the world at risk of infections like rotavirus or pneumococcus. Researchers at Boston Children’s Hospital have developed small-molecule compounds that target a particular receptor to generate an immune response. The vaccine is so effective that in some respects the immune system is stronger than in adults.

newborn-babyMillions of babies under six months old die every year because of infections, and in poor areas of the world birth is the first and unfortunately only time children come into contact with a hospital. A vaccine that effectively boosts immune response becomes thus indispensable.

Newborn babies lack most aspects of immune response, which is why they’re so vulnerable, the researchers however managed to identify a particular white cell receptor – called Toll-like receptor 8 (TLR 8) – that responds to stimulation.

An array of small-molecule compounds were then tested, known chemically as benzazepines, that targeted TLR 8. After many trials, the scientists settled on a particular compound, called VTX-294, which they found triggered a strong immune response in white blood cells in samples taken from newborn cord blood, as well as adult blood. It induced robust production of cytokines—chemicals that rally the immune response—and proved at least 10 times more potent than the best activator of TLR8 known previously.

“The response was not only equal to that in adults, but VTX 294 was sometimes actually more effective in newborns than adults,” notes Ofer Levy, MD, PhD, of the Division of Infectious Disease at Boston Children, the study’s senior investigator.

Moreover, the compound triggered co-stimulatory molecules that enhance immune responses and also strongly activated antigen-presenting cells, a type of white blood cell whose activation induces immune memory. The next step for the researchers is to test VTX 294 on newborn primate babies, whose TLR8 receptor closely resemble humans’.

“This one receptor seems to lead to more adult-like responses—immediate, short-term responses that are more appropriate for fighting infections,” says David Dowling, PhD, co-first author on the study. “We’re excited about the benzazepines because they are already in the clinical pipeline. That advances the potential for using them in a clinical study in human newborns, once they have been proven safe in animal studies.”

Findings were documented in the journal PLoS ONE.

The cholera bacteria.

Virus steals bacteria immune system and kills it

Researchers at Tufts University School of Medicine came across a particular strain of bacteriophage – a virus that infects and replicates within bacteria – that had stolen the functional immune system of the cholera bacteria.  The virus used the bacteria’s immune system against it to replicate and eventually kill the bacteria. The findings hint to the prospect of developing new phage therapies against bacterial diseases like cholera.

The cholera bacteria.

The cholera bacteria.

Until now, scientists have never witnessed this kind of behavior before which has prompted them to believe that phages – typically regarded as primitive particles of DNA or RNA – lack the necessary sophisticated mechanisms to develop an adaptive immune system, which is a system that can respond rapidly to a nearly infinite variety of new challenges.

Andrew Camilli, Ph.D., of Tufts University School of Medicine and also the lead author of the present study, came by the discovery by accident while analyzing DNA sequences of phages collected from stool samples of diseased cholera patients in Bangladesh.  It was then that he identified genes that expressed a functional immune system previously found only in some bacteria.

Each phage is parasitically mated to a specific type of bacteria, and the one for the cholera bacteria is called Vibrio cholerae. Surprised by the atypical genes in the virus, Camilli used phage lacking the adaptive immune system to infect a new strain of cholera bacteria that is naturally resistant to the phage. As expected, the phage failed to penetrate the bacteria, however, when the bacteria were infected with this new strain, the phage rapidly adapted and thus gained the ability to kill the cholera bacteria. This proves that the virus has the necessary tools to adapt and kill the bacteria.

“Virtually all bacteria can be infected by phages. About half of the world’s known bacteria have this adaptive immune system, called CRISPR/Cas, which is used primarily to provide immunity against phages. Although this immune system was commandeered by the phage, its origin remains unknown because the cholera bacterium itself currently lacks this system. What is really remarkable is that the immune system is being used by the phage to adapt to and overcome the defense systems of the cholera bacteria. Finding a CRISPR/Cas system in a phage shows that there is gene flow between the phage and bacteria even for something as large and complex as the genes for an adaptive immune system,” said Seed.

“The study lends credence to the controversial idea that viruses are living creatures, and bolsters the possibility of using phage therapy to treat bacterial infections, especially those that are resistant to antibiotic treatment,” said Camilli, professor of Molecular Biology & Microbiology at Tufts University School of Medicine and member of the Molecular Microbiology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts University.

Phages have been found to be highly prevalent in stool samples infected with bacteria, and since a strain capable of hosting an adaptive immune system was encountered, it seems highly likely that it came naturally. The team is currently working on a study to understand precisely how the phage immune system disables the defense systems of the cholera bacteria, such that effective phage therapies might be developed.

The findings were reported in the journal Nature.

microbial gut flora

Scientists catalog weird microbes in your body – a few pounds of bacteria is healthy for you

By creating this microbiome catalog, researchers hope to figure out the complex interactions between the countless microbes in our bodies and our immune system.

As many already know, germs are not always bad for you – in fact, they are sometimes necessary for a healthy body. But regardless how careless or careful you are with your hygiene, you are carrying with you everyday at least 10,000 species of microbes, weighing a few kilograms, which is actually very little, considering their cells outnumber ours by ten to one.

microbial gut floraThey live on your skin, in your mouth, in your gut: bacteria, fungi and other microbes. But don’t go all ‘eeew’ yet – some of these microorganisms actually help your body remain healthy; many others just peacefully coexist with your cells, but some of them can become really harmful, causing many infections and diseases. The big surprise lied elsewhere: it turns out everybody harbors low levels of harmful microbes, however when a person is healthy, those bugs peacefully coexist with the rest of your cells..

But the next step is what really puzzles doctors and researchers: why do these bugs harm some people and others not? What changes a person’s microbial fauna so much that it puts them in a risk for infection?

“This is a whole new way of looking at human biology and human disease, and it’s awe-inspiring,” said Dr. Phillip Tarr of Washington University at St. Louis, one of the lead researchers in the $173 million project, funded by the National Institutes of Health. “These bacteria are not passengers,” Tarr stressed. “They are metabolically active. As a community, we now have to reckon with them like we have to reckon with the ecosystem in a forest or a body of water.”

You should thank the 100 of trillion of bacteria in your body for good health!

Also, pretty much like with every other ecosystem, your body’s microbial fauna varies depending on your body part. Metaphorically speaking, your skin could be like the rainforest, while your gut could harbor species like an ocean.

Scientists have long know that trillions and trillions of microbes live inside of us, but what they haven’t known so far is that all these types of symbiotic-like and harmful microorganisms coexist in and on our bodies. Some 200 scientists from nearly 80 research institutions worked together for five years on this first-ever census to begin answering those questions by unraveling the DNA of these microbes, with some of the same methods used to decode human genetics.

“We are essentially blind to many of the services that our microbial ecosystems provide — and on which our health depends,” wrote  Dr. David Relman, a Stanford microbiologist.

The next step, he said, is to better understand how the microbiome affects health and disease and to try to improve health by deliberately altering the microbiome. The researchers’ findings were published in the journals Nature and three PLoS journals.

(c) Wyss Institute

Nanorobots made out of DNA seek and kill cancer cells

In what can only be hailed as a breakthrough in the “smart drugs” field, scientists at Harvard University have successfully managed to create nanorobots made out of strands of DNA, folded together by the DNA origami method. These act like drug-carrying recipients, which specifically target various types of cells and deliver complex molecular instructions – like telling cancer cells to self-destruct.

(c) Wyss Institute

(c) Wyss Institute

The shape and structure of the nanobots was critical to their success. The team designed a clam-like device, using DNA modelling software that can compute and complement inputted shapes with the right kinds of DNA strands, of the right helical structure and base pairs, and mix them together.

The DNA clam acts as a container and only opens when it finds its target. To keep its payload unscathed, made out specific molecules with encoded instructions for certain cell surface receptors with which it interacts, the clam is fitted with two locks. Each lock is made out of a DNA strand called an aptamer, specifically designed to recognize a certain molecule. Only when it nears the target, will the aptamer unzip, swinging the claim open, and delivering the payload in the process.

The scientists involved in research were Shawn Douglas, Ph.D., a Wyss Technology Development (Harvard University) Fellow, and Ido Bachelet, Ph.D., a former Wyss Postdoctoral Fellow who is now an Assistant Professor in the Faculty of Life Sciences and the Nano-Center at Bar-Ilan University in Israel.

To demo their creation, Douglas and Bachelet encoded antibody fragments with self-termination instructions for two types of cancer cells – leukemia and lymphoma. Since the two cancer cells communicate differently, they require specific instructions of their own, so the researchers were sure to have the messages written in different antibody combinations.

Smart DNA robots –  miracle drugs of the future?

The nanorobot for leukemia had its locks open in response to molecules expressed on the cancer cells surface, and was loaded with a single molecules which kills cells by disrupting their growth cycles. Millions of such bots were released into a mixture of both healthy and cancerous human blood cells. Only three days afterwards, half of all the cancer cells were destroyed, while absolutely no healthy cells were affected at all. The researchers claim  had they increased the number of payloads into the system, then every leukemia cell would’ve been cleansed.

What’s important to note about this particular system, whose design was heavily influenced by our own natural immune system, is that the active molecules designed to attack a specific cell can be harbored into containers featuring two types of locks. Just like the body’s immune system, the DNA origami nanobots will thus be able to hone in on specific cells in distress, bind to them, and transmit comprehensible signals to them to self-destruct. “It would require that two different signals have to be present to open it, increasing its specificity,” says Douglas.

“This work represents a major breakthrough in the field of nanobiotechnology as it demonstrates the ability to leverage recent advances in the field of DNA origami pioneered by researchers around the world, including the Wyss Institute’s own William Shih, to meet a real-world challenge, namely killing cancer cells with high specificity,” said Wyss Institute Founding Director, Donald Ingber, M.D., Ph.D. “This focus on 9translating technologies from the laboratory into transformative products and therapies is what the Wyss Institute is all about.”

By all standards, this can only be considered a remarkable research, with potentially incredible consequences in medicine. Thoughts, please?

source

Body odour – now essential for online dating!

So, you’ve been talking with him/her on  the Internet for the last four months: personality? check. sense of humor? check. good looks? check. Ready to meet you perfect half? Well, don’t forget about checking the body odor first!

This is not a joke, as weird as it may sound. It won’t be long before online dating websites will allow members to see if they would find their partner’s smell pleasant or would make them go away fast.  And yes, there is serious scientific background to support this initiative: our sense of smell proves to be highly important when choosing someone and it is all a matter of having strong, healthy children. But let’s not rush things.

Biologist August Hämmerli, who started this initiative through the company Basisnote, claims that no matter how well we get along with someone, an unpleasant body smell would make us go away in the end. So, all you have to do in order to avoid possible unpleasant situations is to take a fast saliva test (which is somewhat similar to a pregnancy test) in order to determine your body odor and then enter it as a code in a database; in a matter of seconds you can find out if the person you were flirting with would be pleasant to you and the other way around, if he or she has entered their own code, of course. The whole thing should last for 20 minutes and it’s far from being complicated.

But what factors are involved when liking someone’s smell? Well, it is not a matter of personal hygiene and expensive cologne, but of choosing a partner who is as different genetically from you as possible so as to have strong, healthy children. And even if having a child is the last thing that crosses your mind when flirting with someone, the whole process takes part unconsciously, as the nose’s sensitive receptors are always active.

Mice and other mammals were known to choose their partners by smelling them but until recently no one thought people do the same thing too.

During an experiment in the 90’s female students were given T-shirts that had been worn by men and they were asked to say which smell was the most attractive and which one the least. The man whose immune system differed the most was constantly chosen.

The genes of the MHC, the Major Histocompatibility Complex, which are the ones who carry instructions for various compartments of the immune system, are the ones to be analysed. They bind fragments of foreign proteins such as in the case of an infection and pass them to the defence system, which triggers a reaction. The more different MHC molecules one has, the more pathogents he or she can fight against – and so will the offspring.

In humans, there are about 100 variations of each of the 9 basic MHC genes, and they are the ones to give you your personal scent. The more you differ from your partner, the more he or she will like your smell.

Now the researchers are negotiating with several online dating platforms but they are confident that the idea will catch on quickly. But don’t forget to be charming and funny! This is only the last phase and nobody wants to know how a jerk smells like!

source: ETH Zurich.