The team looked at how NK cells (natural killer cells – a type of immune cell) reacted to Helicobacter pylori. These cells are an important part of the immune system as they can both recognise and kill cells that are infected by viruses and bacteria as well as tumour cells.
“We found that a special type of NK cells was active against the stomach ulcer bacterium,” says Åsa Lindgren. “These NK cells produced cytokines, which are the immune system's signal substances and act as a defence against the intruder.”
The researchers' results suggest that NK cells can play an important role in the immune defence against Helicobacter pylori. Previous research has also shown that a high proportion of NK cells in tumour tissue has contributed to a better prognosis and longer survival for patients with stomach cancer, as these cells help to eliminate the tumour cells.
The researchers therefore believe that activation of the NK cells can play a key role in stopping tumours from developing, and that reduced NK-cell activity can increase the risk of cancer developing. Åsa Lindgren hopes that these findings can be used to develop new ways of diagnosing and treating stomach cancer.
“This would make it possible to diagnose stomach cancer at an early stage, which, in turn, could mean a better prognosis for the patients.”
Thirty years ago Maria de Sousa, then at the beginning of her career, noticed that lymphocytes were attracted to places with surplus of iron. This, together with
1- the fact that the vertebrate immune system (IS) was incredibly more complex that those of its ancestors (and evolution rarely increases complexity, which is energetically costly, unless something is gained)
2- the IS unique capacity to reach everywhere in the body
led her to a revolutionary new idea – could this new complexity be evolutionary sound, because it allowed the IS to perform some important new function, maybe protecting the body against iron toxicity?
In fact iron, although an essential element for most life forms, can also be toxic to these same organisms when free (not attached to proteins). This means that in this form it needs to be “watched” and regulated around the clock. In vertebrates, this is done through hepcidin, a liver protein that “moves” iron between cells and plasma according to the body needs (or potential dangers). The problem is that the hepcidin liver cells have limited mobility so a complementary far reaching iron control system was needed. Lymphocytes, with their unique capacity to move throughout the body were the perfect candidates and since 1978, de Sousa and her group have been chasing this idea.
Much of their work has been done on hemochromatosis – a disease where there are problems in the absorption of iron through the digestive track leading to too much iron in the organism and to its toxic accumulation in the organs.
From this work we know now that hemochromatosis patients also have a defective IS, and more, that their iron overload levels correlate with their lymphocyte deficiency – the less lymphocytes they have the more severe the disease. Work in animal models with iron overload problems or instead, with lymphocyte deficiencies have again found links between excess of iron in the body and deficient IS further supporting de Sousa's “immuno-iron idea”.
And meanwhile, human lymphocytes were shown to produce several proteins crucial for the regulation of iron levels – ferritin, which acts as the body storage of iron (so holding to it when there is too much in the body or releasing it when there is deficiency) and ferroportin, which is the cells' iron “exit door” (again releasing or retaining iron as necessary) . The fact that lymphocytes had both proteins gave them the potential to be a “mobile” and easily “mobilizable” iron-storage compartment, characteristics perfect for an important role in iron homeostasis.
Nevertheless, the exact mechanism how this could happen remained elusive
But hepcidin, the central piece of iron regulation, is known to be also an important player in the immune response what has raised the possibility that it could be in it the clue to this problem. In fact, during infection hepcidin shuts down the “door” through which iron leaves the cell (ferroportin) reducing iron availability in the plasma and thus helping to control infection – as bacteria need iron to divide. And now several studies have shown that hepcidin is produced by a variety of cells involved in the immune response. Finally, last year, a study suggested, for the first time, that lymphocytes were also capable of producing the protein putting the possibility that hepcidin could actually be “the missing link” of de Sousa's theory.
To clarify this hypothesis Jorge Pinto, Maria de Sousa and colleagues at the Institute for Molecular and Cell Biology (IBMC) of Porto University looked at hepcidin production in human lymphocytes in situations of toxic iron concentrations or immune activation, as de Sousa's theory proposed that lymphocytes could play a role in both situations. They found that hepcidin not only was produced by all classes of lymphocytes, but also that its production increased both in the presence of high quantities of iron, and when lymphocytes were activated, backing de Sousa's proposals.
Pinto explains: “We show, for the first time, that lymphocytes can “feel” the toxic levels of iron in circulation and respond by increasing their own capacity to retain it within, restoring “normality”. The same mechanism is seen being used in situations of (iron) demand, such as when the cells are activated by the occurrence of an infection and need to divide.”
They also found something else totally unexpected – that hepcidin was involved in this second mechanism, suggesting an even closer dependence between the two systems than de Sousa had thought.
To Hal Drakesmith, a researcher at the University of Oxford working on the possibility of manipulating iron transport as a way to combat infections such as HIV, malaria and Hepatitis C these results raise particularly interesting questions as he explains “This seems to suggest that control of iron metabolism may be an integral component of lymphocyte immunity. Withholding iron from pathogens is an accepted part of our defence against infection, but a role for lymphocytes in controlling iron transport has not been proposed before.
“Crucially – says Pinto – we still believe that the main regulator of systemic iron levels is the liver but not only are lymphocytes (and not liver cells) able to sense toxic forms of iron, but they are also able to travel and be activated in specific places where the pathogens accumulate helping to control infection. “
These results are a major step to understand the link between the IS and iron and, if confirmed in live organisms –all this work was done on human cells in the laboratory – can be the beginning of a totally different view of what the immune system is and how to approach immunologic problems.
As Hal Drakesmith says “the paper describes several new findings which are highly likely to be of interest and importance to the iron and immunity fields of research” A simple example is the anaemia that usually accompanies chronic inflammatory diseases and that so far can not be clearly explained. Pinto and Sousa's results suggest that lymphocyte chronic activation, so characteristic of these diseases, by leading to hepcidin production could be part of the phenomenon as iron is an integral part of red blood cells.
Pinto, de Sousa and colleagues now plan to go back to those diseases of iron overload associated to immune abnormalities and see if hepcidin proves to be, in fact, the connection between them. Other possibility is the construction of mice without the hepcidin gene in the bone marrow – where lymphocytes develop – to analyse the changes that this could bring to both iron homeostasis and the immune response.
Whatever happens this is a strikingly interesting story with decades of persistence and believe behind it and which, I am sure, still has much to tell us.
By Catarina Amorim
To tackle immunosenescene the team targeted the gastrointestinal tract, which is the main entry for bacteria cells into the body through food and drink and is also the site where 70% of vital immunoglobulin cells are created.
The team asked volunteers aged between 72 and 103, all of which lived in the same care home, to eat one slice of either placebo or probiotic Gouda cheese with their breakfast for four weeks. Blood tests where then carried out to discover the effect of probiotic bacteria contained within the cheese on the immune system.
The results revealed a clear enhancement of natural and acquired immunity through the activation of NK blood cells and an increase in phagocytic activity.
“The aim of our study was to see if specific probiotic bacteria in cheese would have immune enhancing effects on healthy older individuals in a nursing home setting,” concluded Ibrahim. “We have demonstrated that the regular intake of probiotic cheese can help to boost the immune system and that including it in a regular diet may help to improve an elderly person's immune response to external challenges.
The factors instrumental in triggering latent tuberculosis (TB) infection to progress into active disease have long remained elusive to researchers. New insight into the mystery is provided by Professor David Russell, speaking at the Society for General Microbiology's spring meeting in Edinburgh today. His work could help develop innovative strategies for treating the disease.
Professor Russell and his group at Cornell University in New York, USA, have demonstrated that TB-causing bacteria are able to hijack fat metabolism in the host to drive the progression of the disease. The team's research shows that Mycobacterium tuberculosis (Mtb) is able to stimulate macrophages – the immune cells the bacterium infects – to accumulate fat droplets, turning them into “foamy” cells. This cellular transformation can trigger a reawakening of the TB infection from its latent state.
Following initial infection by Mtb, the infected immune cells in the body can clump together in the lungs in a cellular mass that is surrounded by a fibrous cuff. This containing structure, called a
tubercle, physically protects the bacteria from being destroyed by the immune system. This allows them to persist inside the host for years during a latent period in which the host shows no symptoms. The respiratory infection is reactivated only in a small percentage of individuals (often those who are immunosuppressed) in whom it progressively destroys lung tissue. Very little is known about the exact causes of reactivation and the relative roles of the host and the pathogen.
Professor Russell's group discovered that inside the tubercle, surface molecules of Mtb prompted host macrophage cells to take up vast quantities of cholesterol-type lipids from the surrounding blood
vessels. “We think that the lipids in the newly-formed foamy cell are then expelled into the cellular environment, which contributes to the collapse of the tubercle,” he said.
Once freed from their containing structure, the infectious bacteria are able to leak out into the airways where they can progressively destroy lung tissue. “If our model is correct, it has huge implications for
vaccines and chemotherapy programmes. A more detailed knowledge of the bacterium's life cycle and its host interactions will allow us to spot new targets for drugs – opening up new possibilities for treatment,” said Professor Russell.
Professor Latz has recently been recruited by the University of Bonn after working ten years in basic research in the United States. Here, he heads the new Institute for Innate Immunity (Institut für Angeborene Immunität), which has a research focus on the immune mechanisms that cause inflammatory reactions. The innate immune system forms part of the body's own defence mechanism and is able to respond rapidly and directly to a number of alarm signals that appear in the tissue environment. These triggers not only include viruses, bacteria and fungi but also certain crystals and other substances that occur during infections of in stress situations. The strength of the innate immune system is that it can respond very quickly to situations that are of danger to the host. The problem, however, is that it can also overshoot the mark. This type of overreaction is also seen in the case of pneumoconioses such as the black lung, a disease which frequently affects miners. In these lung diseases, a chronic inflammatory reaction is triggered by inhaled crystals made of silicates or asbestos. The molecular mechanisms of crystal recognition are similar to those triggered by cholesterol crystals in blood vessels.
Starting point for developing new drugs
There is still a piece of the jigsaw puzzle missing which researchers need to complete the overall picture. “We don't know precisely how the cholesterol crystals activate the inflammasome”, says Professor Latz. The findings of this study however, offer some starting points for developing new drug therapies. At present, statins are widely used in therapy. Statins reduce the synthesis of endogenous – i.e. the body's self-produced cholesterol and diminish the risk of heart attack or stroke, but they cannot inhibit the absorption of cholesterol from ones diet.
Estimates by the World Health Organization put the number of people now dying from cardiovascular diseases at almost 17 million per year. This means that one in four deaths worldwide is caused by atherosclerosis.
New research from the University of Ulster today offered hope to millions of lupus sufferers worldwide. Dr Emeir Duffy, from the School of Biomedical Sciences, and Dr Gary Meenagh, from Musgrave Park Hospital, Belfast, have discovered new evidence to suggest that fish oil can greatly reduce the symptoms of the disease.
Systemic Lupus Erythematosus (SLE) or Lupus is a disorder of the Immune System, where the body harms its own healthy cells and tissues. The body tissues become damaged causing painful or swollen joints, unexplained fever, skin rashes, kidney problems, complications to the cardiovascular system and extreme fatigue. There are approximately 500 diagnosed cases of SLE in Northern Ireland and it is most common in women of child-bearing age.
At present there is no cure but a key to managing lupus is to understand the disease and its impact. Steroids are the main drug used in the treatment of lupus and they should be administered for the shortest period possible to reduce side-effects. But recently researchers have been looking specifically at its management through diet.
Fish oils contain long-chained polyunsaturated fatty acids which are essential for normal growth and development but also have anti-inflammatory and anti-autoimmune properties. Dr Duffy said: “We have been investigating how fish oil can improve the quality of life for lupus sufferers. “In lupus, the body's immune system does not work as it should. Antibodies, which help fight viruses, bacteria and other foreign substances, are not produced effectively. The immune system actually produces antibodies against the body's own healthy cells and tissues. These auto-antibodies contribute to inflammation and other symptoms of the disease.
“Participants in the study who were taking fish oil supplements, three times per day for twenty-four weeks, saw a reduction in disease activity, an improvement in quality of life and reported an overall feeling of improved health by the end of the study compared to those taking a placebo supplement. Participants taking the fish oil also showed a reduction in fatigue severity, the most debilitating symptom for lupus sufferers. “From our study and from other work, there is evidence that increasing dietary intake of the polyunsaturated fats found in fatty fish can have beneficial effects for lupus sufferers. Good examples of fatty fish include mackerel, lake trout, herring, sardines, tuna and salmon”.
Chronic Fatigue Syndrome (CFS) was originally defined in 1988 when the Center for Disease Control (CDC) in the US brought together a number of researchers who had been investigating a strange syndrome characterized by overwhelming fatigue. This definition however was reviewed by a panel of international experts in 1994 and subsequently revised.
CFS is very difficult to diagnose because the main symptom of fatigue is present in so many other illnesses. However, once other illnesses have been ruled out through laboratory tests and physical examination, a diagnosis of CFS may be given if the following criteria are met:
Clinically evaluated, unexplained persistent or relapsing chronic fatigue that is of new or definite onset (i.e., not lifelong), is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities.The concurrent occurrence of four or more of the following symptoms: substantial impairment in short-term memory or concentration; sore throat; tender lymph nodes; muscle pain; multi-joint pain without swelling or redness; headaches of a new type, pattern, or severity; unrefreshing sleep; and post-exertional malaise lasting more than 24 hours. These symptoms must have persisted or recurred during 6 or more consecutive months of illness and must not have predated the fatigue.
The full text of the revised definition can be found at the CDC website: http://www.cdc.gov/ncidod/diseases/cfs/about/definition/index.htm
Symptoms and General Information
Obviously, as is implied by the various names, fatigue is the major symptom in CFS. People often have the misconception that this is the only symptom and hence they assume that sufferers simply like to complain about the normal tiredness that everyone experiences after a day at work etc. CFS is actually much more than fatigue, and the fatigue experienced is a lot more severe than simple tiredness. The following is a list of the major symptoms of CFS.
- Exercise Intolerance
- Severe Malaise
- Muscle and Joint Aches
- Cognitive Dysfunction
- Chronic Headache
- Balance Disturbance
- Recurrent Sore Throat
- Mood and Sleep Disturbances
- Abdominal Pain/Digestive Disturbances
- Sensitivity to Light and/or Sound
- Visual Disturbances
- Skin Sensitivity
The cause, or causes of ME/CFS are still not clear. There are a number of theories that have been proposed, the main ones propose the following factors as the cause or causes of the illness:
- Viral Infection
- Mycoplasma Infection
- Immune or Endocrine Dysfunction
- Autonomic Nervous System Dysfunction
- Environmental Toxins
- Genetic Factors
- Candida Overgrowth
- Gut Dysbiosis
- Heavy Metal Sensitivity
- Emotional Stress or Trauma
There may be a large number of abnormalities in multiple body systems in CFS patients. These abnormalities centre around the nervous, endocrine and immune systems and the way these interact with each other. Although these abnormalities have been identified it is still unclear which are causes and which are effects. New research will hopefully shed more light on this but until then doctors who are seeing the best results with patients seem to be those who take a multifactorial approach and try to correct as many of the abnormalities discussed as they possibly can, using currently available treatments.