The Immune System in Health and Disease

Written by Craig Wiesenhutter, M.D.

Multimedia and Flash Template by Craig Wiesenhutter, M.D.

Our bodies are under constant attack by a wide variety of organisms. These bugs would like to invade us and then turn our bodies into their happy home. If that wasn’t bad enough, they also try to make use of us as a source of nutrition. These invaders want nothing less than “room and board” – at our expense!

Fortunately, our bodies have a very beautiful and remarkable system to defend against such invaders: It is called the immune system. The importance of the immune system can’t be overstated. Children born with serious immune system defects often die from infections at an early age. Even more important for understanding certain disorders that will be discussed in this patient education sheet, the different parts of the immune system sometimes miscommunicate with each other, leading to unnecessary activation of the system. When this happens, the immune system mobilizes to defend the body, even though no invader exists. The way that the immune system makes mistakes determines what types of problems will occur in the body, and where these problems will occur. For these reasons, it is very worthwhile to learn more about the immune system, its parts, and how it works.

The body’s army

The immune system defends the body much as an army defends a country. This analogy is useful when thinking about the immune system. Just like an army, the immune system uses different types of troops and weapons. The troops consist of different kinds of white cells. The white cells that issue most of the orders (similar to officers) are the lymphocytes and macrophages. The white cells that just do what they’re told (similar to enlisted soldiers) are called neutrophils or polys. These cells fiercely and fearlessly enter the infected area (the battlefield) consuming and destroying enemy bugs in large numbers. The dead remains of polys make up the majority of what’s called pus in abscesses. Someone has to do it.

The weapons of the immune system are many and very powerful. Among the best known immune system weapons are antibodies, which play many different roles. Antibodies can act as both villains and heroes; they can be the cause of tissue injury, or the source of wonderful new treatments.

The white cells and antibodies guard and patrol all areas of the body. The most common sites of invasion by bugs include the skin, lungs, stomach, and intestines. When a bug invading the body is detected, all sorts of alarms are raised. These warning signals come in the form of molecules produced and secreted by the white cells at the site of infection. These molecules cause a number of important events to happen. Nearby blood vessels dilate, for instance, and the cells lining the blood vessels spread apart. These blood vessel changes allow more blood to enter the area, which helps to deliver more white cells and weapons necessary to kill the invading bugs. These blood vessel changes also initiate an important process known as inflammation.

Because the blood vessels in the infected area become so dilated, the region becomes redder, hotter, and more swollen than normal. Many of the chemicals generated in the inflammatory response also stimulate nerve endings, causing pain. The pain notifies us that we have a problem, and prompts us to protect the inflamed area.

Meanwhile, molecules that issue a “call-to-arms” to other immune system soldiers (cytokines) also travel in the blood stream to distant sites of the body, causing fever and altering organ function so that the body is better able to fight off the infection. In the vast majority of cases, inflammation is a good thing, and at times it can be life saving. Remember that the next time you get the flu. Much of what’s making you feel rotten stems from the products of your normal immune system in action.

Misguided fire power

In rare circumstances, the immune system runs amok, and the inflammatory response occurs inappropriately in areas that are not infected by bugs. This abnormal attack by the immune system on oneself is called autoimmunity (“auto” is a Greek word for self). The location and intensity of an autoimmune attack determines the “signs and symptoms” of a given disorder: what is felt and seen by a patient, and what parts of the body are affected.

For example, an autoimmune attack on the skin will lead to redness, and the skin will become hot, itch, or hurt. We refer to this problem as a “skin rash.” If this abnormal inflammatory response involves a joint, the joint swells and becomes hot and tender. Because of the extra fluid and blood that has entered the joint, the person affected will experience stiffness, and movement of that joint may be hindered. When the immune system attacks joints, the process is called inflammatory arthritis; there are several kinds of inflammatory arthritis.

To accomplish its mission of protecting us from infection, the immune system must be able to deliver troops and weapons rapidly to any part of the body. A bug deposited by a splinter under the skin, for instance, could multiply and travel to lymph nodes, liver or, via the bloodstream, to just about anywhere in the body. The immune system must have the capability to respond to these secondary sites of infection as well. This means, however, that when autoimmunity occurs, just about any part of the body can be struck.

In the most common type of inflammatory arthritis, rheumatoid arthritis (RA), the immune system most frequently attacks the wrists and the small joints of the hands closest to the wrist, sparing the small joints closest to the fingernails. In RA, autoimmune attack is commonly directed towards the lubrication systems of the eyes, mouth, and skin, causing dryness of these tissues (a syndrome referred to as Sjogrens, pronounced “show grens”). The pattern of joint involvement (which joints are swollen and tender), and the other locations of the body that are attacked (lungs, kidneys, heart lining) greatly aids doctors in reaching a diagnosis, since it reflects upon what has gone wrong with the immune system.

In psoriatic arthritis, the pattern of joint involvement is usually different from that seen with RA. Often in psoriatic arthritis, single, isolated joints are affected, or a whole digit will swell up and looks like a sausage. The skin is typically involved as well, with very characteristic changes of redness and scaliness. The presence of a rash and the pattern of arthritis lead doctors to the correct diagnosis.

Inflammation detectives

Rheumatologists have been trained as “inflammation detectives”. When you consult a rheumatologist, he or she will ask about your medical history. What hurts? Where does it hurt? How long have you had the problem? Have you had a fever? Do you have dry eyes? Are you short of breath? (This last question is important, because the immune system can attack the lungs). The rheumatologist will listen to your answers, and then probably ask you more questions.

The rheumatologist will then examine you to determine whether a sore joint you’re complaining about is red, hot or swollen. A physical examination also enables the rheumatologist to determine whether that sore spot is actually outside the joint, right where the tendon attaches to the bone, or under a muscle. If so, the problem may not really be arthritis, but rather may be bursitis or tendonitis. If the accumulation of immune cells can be felt in the joint, the condition may be synovitis. If the lungs make abnormal noises when you breathe deeply, this suggests that they may be under attack by the immune system as well.

Then your rheumatologist might take blood samples for tests. When the immune system is mounting a defense, either normal or not, it produces molecules that can be detected in the blood. Important examples include the erythrocyte sedimentation rate or ESR and the C reactive protein or CRP, which indicate the presence and/or degree of inflammation.

Immune system defects in certain diseases will produce characteristic molecules. Examples of tell-tale molecules include the rheumatoid factor (RF), which is found in the majority of patients with RA, and anti-nuclear antibodies (ANA) in systemic lupus erythematosis. However, it is a common mistake for patients to think that just because their blood tests positive for RF (indicating possible RA) or ANA (indicating possible lupus), that means they definitely have the disease. In fact, about 5% of healthy individuals also test positive for these factors, so that a definitive diagnosis can only be reached after a combination of criteria are met. For instance, even if your joints are sore, and you also have a positive blood test for RF, you do not have active RA if your joints are not inflamed.

Lastly, your rheumatologist may request x-rays of joints, to determine whether remnants of an earlier bone or tissue injury might have caused an immune response at that site. In addition to helping confirm the pattern of joint involvement, these x-rays can reveal clues, such as little holes in the bones called erosions, which can be very helpful in forming a diagnosis, and deciding how severe the disease is in an individual patient.

In addition to rheumatoid arthritis, psoriatic arthritis and lupus, other important autoimmune diseases include ankylosing spondylitis, which primarily affects the spine, and several diseases caused by an immune attack on blood vessels, collectively called vasculitis. The most clinically important vasculitis is temporal arteritis (also called giant cell arteritis). In yet another disorder, Scleroderma, the altered immune system activity leads to thickening of the connective tissues of the skin and many other organs.

Points to remember

Our immune system constantly defends us against organisms that would otherwise do us harm, and the inflammatory response is one of the most important mechanisms in this defense. Given the complexity of the immune system, the billions of cells involved, and the need for tight coordination of all the various parts, it is not surprising that errors occasionally occur.

In rare cases, defects in the immune system lead to chronic disorders, called autoimmune diseases, that can be diagnosed by analyzing the way in which the inflammatory response is disturbed. Accurate diagnosis of an autoimmune disease has become increasingly important because expanding knowledge about these disorders has lead to new and improved therapies. These treatments are most effective when begun as soon as possible after the autoimmune attack has begun.

If you suspect you have an autoimmune disorder, consult with a rheumatologist, who has been specifically trained to diagnosis and treat these conditions.