Immune system: In-house sentinels against disease

For centuries physicians believed that diseases were caused by an imbalance in the "four humours" -- blood, phlegm, yellow bile and black bile. These notions were swept away in the 19th century by the advent of modern medicine. Bit by bit it laid bare a realm of microscopic warfare where the body's complex -- but also sometimes flawed -- defence fought in close-quarter combat against germs and viruses. The 2011 Nobel Prize for Medicine was awarded to three scientists who have done more than anyone to lay bare the two-tier structure of the immune system. They are Bruce Beutler of the United States, Jules Hoffmann, born in Luxembourg but a naturalised French citizen, and Ralph Steinman of Canada. Working separately, they discovered key secrets in "innate" immunity, our first-line response to pathogens, and its dovetailing with the second-line defence known as "adaptive", or acquired, immunity. Their achievements are central to vaccine development, which depends on priming the immune system to target pathogens, and to new treatments against cancer, a process in which tumorous cells proliferate unchecked. "(It's) very important work, which has opened not only our understanding of the immune system but also led to some practical new ways to target immune responses, including more potent vaccines," said Seth Berkley, head of the GAVI Alliance, which promotes immunisation in poor countries. In a case with few parallels in medical history, Steinman harnessed this knowledge to design an experimental drug to treat his own pancreatic cancer, Rockefeller University in New York said on Monday. Steinman died on Friday at the age of 68, just three days before the Nobel announcement. But the drug extended his life by four years after diagnosis, beating the odds for a disease where patients often die within months. The immune system can be described as an intricate and dynamic network of millions upon millions of cells, each with their speciality. Beutler and Hoffmann identified receptor proteins that trigger the molecular cascade which is the innate immune system. This defence is a generalised call to arms, mustering platoons of immune cells to initiate inflammation, a chemical process that seeks to establish a physical barrier against penetration beyond the microbe's entry point. The next line of defence, the innate system, is slower to respond but more adaptive. It teaches immune cells through a process called antigen presentation to recognise and remember the specific intruder for future alerts. Steinman's work found that so-called dentritic cells regulate the function of the body's natural "killer cells", called lymphocytes, including T-cells and B-cells. Dendritic cells play a key role in the onset of several immune responses, including graft rejection, resistance to tumours, infections and autoimmune disease in which the body fights against itself. In an example of the practical outcome of his work, the drug Etanercept is now widely used for the treatment of arthritis, Crohn's disease, psoriasis and other forms of inflammation.