MRC National Institute for Medical Research, London
Science for Health
2011 meeting - Curses and benefits of parasites
In an era when humans are more hygiene-conscious than at any time in history, we still need to know more about the fascinating biology of human parasites. The parasite that is responsible for malaria, Plasmodium, causes untold death and disease. The Schistosoma parasite causes extensive morbidity, but also offers clues to the important health issues of autoimmunity and allergy.
The first talk is from a parasitologist who studies the malaria parasite to find targets for drugs. The second is from an immunologist who is interested in the origins of autoimmunity and allergy.
Malaria: a complex parasite with powerful friends (mosquitoes) - Dr Tony Holder
Many infectious diseases have left indelible marks in the human genome that bear witness to our battles for survival against extremely dangerous foes. However, the intensity of the struggle with malaria is perhaps the most obvious. At least seven genetic diseases, including sickle cell anaemia and thalassaemia, affect millions of people in the tropics. They confer some resistance to malaria but also cause a significant burden of ill-health. Malaria is caused by different species of Plasmodium, a single-celled parasite that is transmitted by mosquitoes. In the 19th century perhaps half of the world’s population was at risk of malaria and perhaps one tenth died of it, but determined efforts to eradicate the mosquito have made the disease less prevalent. Even now, up to 300 million people have the disease and more than one million people die each year. Although in the 1960s insecticide spraying offered hope of eradication, the disease is now advancing again and may gain momentum with global warming.
The mosquito collects blood from victims by using its proboscis like a tiny hypodermic syringe and injects the victim with the Plasmodium parasites contained in its saliva with extraordinary efficiency. They use special organelles to invade red blood cells where they multiply, producing a fiendish mixture of chemicals that cause the notorious manifestations of the disease (fevers, severe anaemia, brain damage and more). The complexity of the parasite’s life-cycle makes the disease more difficult to control than many bacterial or viral diseases. Widespread use of insecticide-treated bednets helps to keep the mosquitoes away. Anti-malarial drugs are available, although drug-resistance is becoming common. New drugs and an effective vaccine are needed. Better drugs and mass vaccination to protect against all the different forms of malaria may one day help eradicate human malaria from the world.
The hygiene hypothesis and the origins of allergy and autoimmunity - Dr Mark Wilson
The human immune system has a remarkable capacity to deal with infectious microbes effectively because it can recognise billions of foreign chemicals as antigens and yet tolerate the distinctive collection of potential antigens in our own bodies (self). For a significant number of people, this tolerance breaks down, leading to the development of autoimmune and allergic diseases. These are becoming increasingly common. The hygiene hypothesis attributes this breakdown of tolerance to a lack of childhood exposure to microbes, thereby limiting the development of the immune system.
An effective immune response must have “effector” pathways, responsible for attacking microbes (viruses, bacteria or parasites) and also a “regulatory” pathway, required in order to resolve inflammation. Reduced exposure to microbes fails to generate a regulatory response, which may lead to the development of autoimmune and allergic reactions.
A third dimension to the hygiene hypothesis is the part played by chronic pathogens such as the parasitic worm Schistosoma which enters a close relationship with the host by subverting the immune system. These parasites inhabit their hosts for many years because they have evolved elaborate ways of switching off the effector pathways of the immune response and enhancing the regulatory pathways, with the net result of a dampened immune system. Evidence that pathogens, particularly chronic pathogens directly interfere with our immune system is now very clear. Mark Wilson will describe the approach he uses to study the causes of allergic airway disorders and autoimmune reactions in mice and what we can learn from chronic pathogens, such as Schistosoma.
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