2.4: Our Immune Army
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Scientist know a lot about the body's organ systems, but much more remains to be discovered. To design "smart" drugs that will seek out diseased cells and not healthy ones, researchers need to understand the body inside and out. One system in particular still puzzles scientists: the immune system.
Even though researchers have accumulated vast amounts of knowledge about how our bodies fight disease using white blood cells and thousands of natural chemical weapons, a basic dilemma persists—how does the body know what to fight? The immune system constantly watches for foreign invaders and is exquisitely sensitive to any intrusion perceived as "non-self," like a transplanted organ from another person. This protection, however, can run afoul if the body slips up and views its own tissue as foreign. Autoimmune disease, in which the immune system mistakenly attacks and destroys body tissue that it believes to be foreign, can be the terrible consequence.
The "Anti" Establishment
Common over-the-counter medicines used to treat pain, fever, and inflammation have many uses. Here are some of the terms used to describe the particular effects of these drugs:
- ANTIPYRETIC—this term means fever-reducing; it comes from the Greek word pyresis, which means fire.
- ANTI-INFLAMMATORY—this word describes a drug's ability to reduce inflammation, which can cause soreness and swelling; it comes from the Latin word flamma, which means flame.
- ANALGESIC—this description refers to a medicine's ability to treat pain; it comes from the Greek word algos, which means pain.
The powerful immune army presents significant roadblocks for pharmacologists trying to create new drugs. But some scientists have looked at the immune system through a different lens. Why not teach the body to lunch an attack on its own diseased cells? Many researchers are pursuing immunotherapy as a way to treat a wide range of health problems, especially cancer. With advances in biotechnology, researchers are now able to tailor-produce in the lab modified forms of antibodies—out immune system's front-line agents.
Antibodies are spectacularly specific proteins that seek out and mark for destruction anything they do not recognize as belonging to body. Scientists have learned how to join antibody-making cells with cells that grow and divide continuously. This strategy creates cellular "factories" that work around the clock to produce large quantities of specialized molecules, called monoclonal antibodies, that attach to and destroy single kinds of targets. Recently, researchers have also figured out how to produce monoclonal antibodies in the egg whites of chickens. This may reduce production costs of these increasingly important drugs.
Doctors are already using therapeutic monoclonal antibodies to attack tumors. A drug called Rituxan® was the first therapeutic antibody approved by the Food and Drug Administration to treat cancer. This monoclonal antibody targets a unique tumor "fingerprint" on the surface of immune cells, called B cells, in a blood cancer called non-Hodgkin's lymphoma. Another therapeutic antibody for cancer, Herceptin®, latches onto breast cancer cell receptors that signal growth to either mask the receptors from view or lure immune cells to kill the cancer cells. Herceptin's actions prevent breast cancer from spreading to other organs.
Researchers are also investigating a new kind of "vaccine" as therapy for diseases such as cancer. The vaccines are not designed to prevent cancer, but rather to treat the disease when it has already taken hold in the body. Unlike the targeted-attack approach of antibody therapy, vaccines aim to recruit the entire immune system to fight off a tumor. Scientists are conducing clinical trials of vaccines against cancer to evaluate the effectiveness of this treatment approach.
The body machine has a tremendously complex collection of chemical signals that are relayed back and forth through the blood and into and out of cells. While scientists are hopeful that future research will point the way toward getting a sick body to heal itself, it is likely that there will always be a need for medicines to speed recovery from the many illnesses that plague humankind.
A Shock to the System
A body-wide syndrome caused by an infection called sepsis is a leading cause of death in hospital intensive care units, striking 750,000 people every year and killing more than 215,000. Sepsis is a serious public health problem, causing more deaths annually than heart disease. The most severe form of sepsis occurs when bacteria leak into the blood-stream, spilling their poisons and leading to a dangerous condition called septic shock. Blood pressure plunges dangerously low, the heart has difficulty pumping enough blood, and body temperature climbs or falls rapidly. In many cases, multiple organs fail and the patient dies.
Despite the obvious public health importance of finding effective ways to treat sepsis, researchers have been frustratingly unsuccessful. Kevin Tracey of the North Shore-Long Island Jewish Research Institute in Manhasset, New York, has identified an unusual suspect in the deadly crime of sepsis: the nervous system. Tracey and his coworkers have discovered an unexpected link between cytokines, the chemical weapons released by the immune system during sepsis, and a major nerve that controls critical body function such as heart rate and digestion. In animal studies, Tracy found that electrically stimulating this nerve, called the vagus nerve, significantly lowered blood levels of TNF, a cytokine that is produced when the body senses the presence of bacteria in the blood. Further research has led Tracey to conclude that production of the neurotransmitter acetylcholine underlies the inflammation-blocking response. Tracey is investigating whether stimulating the vagus nerve can be used as a component of therapy for sepsis and as a treatment for other immune disorders.