How the Immune System Can Go Wrong

Excerpted from
UltraLongevity: The Seven-Step Program for a Younger, Healthier You
By Mark Liponis, M.D.

The immune system is remarkable for its size, complexity, and efficiency. But like the human beings in whom it resides, the immune system can be quite fallible. The weakness lies primarily in two areas: on the one hand, the potential to be overpowered by invaders, and on the other, overstimulation.

The first problem occurs when our immune system musters an inadequate response to foreign invaders, who then pass through the defense network. We know this process all too well-an infection takes hold and our immune system isn't capable of fighting it. This might happen when a particularly nasty infection flares from a killer germ, causing, for example, typhoid, diphtheria, or tetanus.

Another possibility is that the immune system itself has been rendered almost powerless by some invader (such as HIV), by certain conditions (such as immunodeficiency diseases), or by an immune-suppressing medication (such as antirejection drugs taken by transplant recipients, or, more commonly, steroids such as prednisone or cortisone). In such cases, our immune system can't defend us from the invaders that it would otherwise easily dispose of.

Unfortunately, failure of the immune system remains the primary killer in developing nations, which have historically lacked access to modem vaccines and antibiotics, as well as to proper sanitation, clean water, and healthy food. (In fact, in developing countries millions die every year simply from contaminated water.) Diseases such as tuberculosis, malaria, and cholera are still among the world's biggest killers.

In a way, the type of aging process discussed in this book is specifically a disease of people in affluent, developed nations. In Nigeria, there are few nursing homes for Alzheimer's patients. In the Sudan, few bypass surgeries are performed. Only a small number of significant problems from the diseases of aging exist in the developing world, because people often don't live long enough to experience them.

In other words, in third world countries, the immune system struggles just to do its job against the vast array of invaders still prevalent in the landscape. The situation is different in the developed world. Rather than infectious diseases, more than 50 percent of American deaths in 2005 were due to autoimmune problems, while only 4 percent were caused directly by infection (flu, pneumonia, sepsis). The remainder of American deaths include about 6 percent caused by injury (accidents, suicide) and 23 percent by cancer (aided and abetted by the immune system, as we'll discuss later).

In America, we have the luxury of the technological and economic advantages that prolong life and, in part, contribute to the development of an aging population and the attendant diseases of aging.

This is not a bad thing, nor something about which we should feel guilty. After all, we are in a position to conduct the best research on aging and the immune system. Once medicine and public health measures are able to rid the external environment of the sources of attacks on our health, we may find a cure for the diseases of aging too-saving developing nations from having to reinvent the wheel in regard to bolstering the immune system.

Immune Activation: The CRP Test

In our environment, the more dangerous peril occurs when the immune system becomes overactive.

The first research group to study and recognize the association between immune activation and conditions such as heart disease, stroke, and poor circulation was led by Dr. Paul Ridker, of Harvard Medical School, in the mid-1990s. While conducting research on the heart, Ridker noticed high levels of C-reactive protein (CRP) in the blood of patients who had had heart attacks.

The most common test for immune system activation is a CRP blood test-the higher the CRP level, the more active the immune system. (Another common way to measure immune system activity is sedimentation, or sed, rate. Sed rate measures how fast red blood cells settle to the bottom of a test tube of blood; the faster they settle, the more active the immune system, because when the immune system is active, the blood contains more proteins, such as CRP and other cytokines that adhere to red blood cells and make them stick together. That causes the red blood cells to fall, or "sediment," more quickly, raising the sed rate.)

Repeated studies by Ridker's group showed that CRP levels were also a better predictor of heart attack than cholesterol, blood pressure, family history, or any other of the traditional risk factors.

Although a basic CRP test had been available for several years before Ridker's research, his group was instrumental in developing a far more sensitive test able to detect CRP levels to a much greater degree of accuracy.

Development of this highly sensitive CRP test (hs-CRP) was a key step in identifying the link between immune activation and heart disease, because Ridker found that even slightly elevated levels of CRP increased the heart attack risk. The hs-CRP test was more accurate than any other test in medical history at helping the researchers distinguish between people who were likely to be safe from heart attack and those who were at risk.

Many other researchers have since confirmed Ridker's findings. What's even more interesting is that elevations of hs-CRP have now been found to predict many other diseases besides heart disease. Elevated hs-CRP has been found to be an excellent predictor of the following: abdominal aortic aneurysms, Alzheimer's disease, atrial fibrillation (irregular heartbeat), diabetes, high blood pressure, macular degeneration (a leading cause of blindness), osteoporosis, stroke, sudden cardiac death, and colon, prostate, and other cancers.

Note that CRP levels become elevated even before the diseases themselves are present, meaning that immune activation precedes the diseases.

Scientists are just beginning to understand and identify the specific involvement of the immune system in actually causing these diseases. What medical researchers have come to realize, thanks in part to the pioneering work of people like Dr. Ridker, is that friendly fire can take place just as easily inside a body as outside it.

Medically speaking, what is friendly fire? In a real war, innocent bystanders can be hurt. The same is true inside your body. If your immune system is waging a battle to defend you from a threat, its ammunition may accidentally harm innocent bystanders-your heart, brain, blood vessels, pancreas, or any other guiltless spectator that the immune system isn't trying to destroy, but that may nonetheless become injured by friendly fire.

In the process of protecting us, the immune system aims to target a specific infection, but it is not able to coordinate its forces so precisely that only the infection itself is attacked. When its many weapons hit other parts of the body, it can create serious problems.

It's easy to see why the balance between protection and destruction in our immune system is critical, because when it is out of whack, illnesses can result.