Professor Rashika El Ridi (Egypt. Cairo), 2010 laureate of the L’Oréal-UNESCO program For Women in Science, is well aware of the great advances in immunology that have made her own research possible. She observes the impact on her own work, and expresses gratitude for this knowledge, which she hopes will help to improve the health of millions.
“It’s a vicious circle, with a vicious origin.” Professor Rashika El Ridi, of the Faculty of Sciences at Cairo University in Egypt, is describing the subject of her professional life’s work. Schistosomiasis, an infection caused by a parasitic worm, is second only to malaria in terms of socioeconomic damage done, and plagues over 200 million people across Africa, Asia and Latin America. When she talks about her work to stamp out this disease, Professor El Ridi, laureate of the 2010 L’Oréal-UNESCO For Women in Science award, repeatedly expresses her gratitude to the many immunologists, past and present, who laid the groundwork for her own research. “You have no idea of the number of great scientists who have contributed to the explosion of knowledge in immunology.”
Today, the field of immunology recognizes Jules Hoffmann, Bruce Beutler and Ralph Steinman among these significant contributors to the field and, for El Ridi, the impact they have had on her own research is clear. The immune system consists of two branches: the innate immune system, the body’s first line of defense in fighting off foreign invaders, and the adaptive immune system, which launches a more targeted attack against specific bacteria, viruses and other microbes. Hoffmann and Beutler made discoveries concerning innate immunity, while Steinman discovered an important link between the two branches. And both play a role in El Ridi’s search for a vaccine.
The Egyptian immunologist is extremely motivated to find a vaccine against schistosomiasis due to three factors that make it so destructive. First, the disease affects primarily children, in poor, rural populations. The parasite is transmitted via fresh water, and kids are particularly at risk, as they swim and play in fresh-water canals. A second, insidious characteristic of the disease makes people with schistosomiasis prone to co-infection by other agents. This means they are more likely to catch malaria, tuberculosis, or HIV. While treating for one of these diseases, medical professionals often neglect to assess a patient’s schistosomiasis status, leading to exacerbation of both diseases. This third vicious point completes the circle evoked by Professor El Ridi.
“It is for these three reasons that we decided to devote all the resources [of our lab] to developing a vaccine. We want to eradicate this disease from the planet.”"
Her strategy in this quest involves understanding the basic biology of the parasitic worm, the schistosome, in order to identify the ideal method of attack. Development of the vaccine that she is currently testing depended on knowing what happens from the beginning of the worm’s lifecycle, when the parasite first infects a person. To begin, the larva of the worm, found in infested waters, attaches to a person’s skin and secretes enzymes that dig down through the surface. Its destination is the bloodstream, where adult worms can live for up to ten years, or more.
This initial attack on the body is already sending signals to the innate immune system, via specific receptors on the surface of white blood cells called toll-like receptors (TLRs). In 1996, Jules Hoffmann was studying immunity in fruit flies when he noticed that, without a certain molecule on the cells’ surface, the flies were unable to fight off bacterial and fungal infections. This molecule, called Toll, was already known to play a role in development. Hoffmann revealed that it was also required to alert the immune system to the presence of invaders. Later, other versions of the same molecule were identified in mammals, and they grew into a whole family of receptors, the TLRs. In 1998, Bruce Beutler made the critical discovery that one of these molecules, TLR4, served as a receptor for a specific molecule commonly found on the external surface of bacteria. In its presence, TLR4 raises the alarm, activating the immune system. It is now known that all TLRs recognize various microbial elements—bacterial lipids or viral proteins, for example—and help to trigger an immune response. For El Ridi, these discoveries “revolutionized immunology.”
She now knows that, from the very first stage of infection, the presence of the schistosome worm is detected by the innate immune system, via the activation of TLRs. As the parasite makes its way toward the blood vessels, where developing larvae and adults are found, it releases substances that are noticed by patrolling immune cells, the dendritic cells. Their role in immunity was identified in 1973 by Ralph Steinman. These immune sentinels roam the body, reaching their extensions into the tiniest spaces between cells, searching for signs of intruders. In a schistosomiasis patient, they detect the molecules secreted by the worm, and trigger production of other agents of the immune system that follow the migrating parasite. Professor El Ridi employs a metaphor of “the hunt” when describing the interaction between the parasite and these immune effectors: like hounds follow the scent trail of an animal, these cells track the schistosome.
“Steinman’s dendritic cells thus present the antigen, [the “foreign” molecule that triggers an immune response], to the officers of the immune system, the T lymphocytes.”"
T lymphocytes, or T cells, are a type of white blood cell. When activated, depending on the variety, they may attack and kill foreign invaders, or mobilize other cells to do the job. In the case of schistosomiasis, Dr. El Ridi discovered a new phenomenon. The initial signal of invasion, given off when the larva enters the skin, also affects T lymphocytes. But, this time, in an undesirable way for the victim. It causes the T cells to produce less of the chemical messengers that would activate basophils and eosinophils, the immune cells required to destroy the parasite. The message isn’t sent, the necessary troops are held at bay, and the parasitic worm manages to avoid destruction.
“What I want now,” says El Ridi, "is a vaccine to induce [the chemical messengers] who will bring basophils and eosinophils from the start.”"
Professor El Ridi enthusiastically recognizes that she couldn’t do her work without discoveries such as those of Hoffmann, Beutler and Steinman.
“I am so grateful to all the immunologists who provided all this knowledge. In developing countries, we don’t have the means, the resources, to do all this work, but we can adapt,”"
she explains, take the advances that came before and build on them.
“There should be a prize just for immunology,” she insists, “…for 30 or 300 people!”"
Her appreciation for this work that provided the foundations for her own research is genuinely heartfelt, and will undoubtedly be shared by millions, if the El Ridi lab succeeds in its quest for a vaccine.
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To find out more: World Health Organization, Schistosomiasis Fact Sheet http://www.who.int/mediacentre/factsheets/fs115/en/index.html
Schistosome Life Cycle Animation http://www.wellcome.ac.uk/en/labnotes5/animation_popups/schisto.html Ralph Steinman: Introduction to Dendritic Cells http://lab.rockefeller.edu/steinman/
National Institute of Allergy and Infectious Diseases, “Immune System” http://www.niaid.nih.gov/topics/immuneSystem/Pages/default.aspx