Speaker script, episode 4: Defence Not Wanted A moment of distraction, the wrong reaction, in just a fraction of a second it happens. Any one of us can become victims of an accident who never regains consciousness. Almost no one is prepared for that. Very few of us have given a thought to donating our organs in the event that they we brain dead. About 14,000 patients in Germany are waiting for a heart, a liver, kidneys or lungs. But barely 1,000 citizens a year are prepared to allow the removal of their organs, although this could relieve other people from severe suffering or even save their lives. Some people have reservations about organ donations. But any of us can find ourselves in a situation in which no other method of treatment will help. Then a new organ is the only hope. Patientin: „I had a liver transplant four years ago. I had fallen ill with a very serious liver disease fifteen years before, and it was the last straw within my grasp to live at all."" Patient: „I was very grateful from the very first moment that there was one person who had been willing to do this and felt that fate had determined that one person would end his life, but that I would be given the chance to continue to live." The doctor Andreas Hatopp on his way to work. He has been living with another person's kidney for thirteen years. He works in the radiology department of a large hospital. People who have received transplants are more susceptible to infections because their immune systems have been partially repressed. But Andreas Hatopp did not give up his professional dream. Even as a child he wanted to become a doctor. That was when his kidney problems began. Hatopp: „The first thing I noticed was that my school work began to deteriorate badly, at times becoming worse very rapidly, e.g., from a mark of good to unsatisfactory. Within three-fourths of a year, the kidney failure had progressed to such an extent that I had to undergo dialysis, i.e., a blood cleansing procedure. You have to go to the station three times a week and spend four to five hours being dialyzed, a situation which takes up a considerable amount of your time. Most of the patients are pretty tired afterward, just as I was, so that the rest of the day is also lost. I had to follow a strict diet which was low in protein and which didn't necessarily taste so good, plus I also needed an awful lot of medications, at times up to twelve different ones and up to 50 pills a day." No artificial apparatus can fully achieve the level of performance of a natural organ. This is also the case with kidneys. Only a transplant allows the patient to lead an almost normal life. Because every person has two kidneys, it is also possible to take a donated organ from a living person. Andreas Hatopp received his kidney from his mother. As soon as there is sufficient blood flow to the transplanted organ, it starts to work. The doctors recognize this when the first drops of urine appear. Hatopp: „I had two rejection reactions during the first half-year after the transplant; a lot of patients, although not all, have them, the doctors were able to treat them with medication. And after this half-year, when I had these difficulties, I really did well. I can eat what I want, I can drink what I want, I need far less medicine, just a very small number of medications, and I can also hold up under physical activities as I want, the intellectual abilities - such as what I mentioned about school work - have improved, and you really have, you can really lead a completely normal life." When Christiaan Barnard performed the first heart transplant in 1967, transplants were still exceptional cases. Louis Washkansky, the first patient, survived only three weeks. Nor did the following transplants have long-term success. Some people died from infections which the repressed immune system was unable to deal with. In other cases, the immune system was not repressed enough, and it rejected the foreign organ. Animated film (length: 3:59 min) Life as an individual begins with the very first division of cells. All of the cells of a body bear their own, unique features, which normally vary from one person to the next. Evolved to ensure that the body remains intact, the immune system rejects everything which has foreign features, including transplanted organs. All of the cells of the immune system begin their career as simple stem cells in the bone marrow. Part of them move to the spleen and the thymus. Here is where the T-cells learn to recognize and fight off foreign intruders. The T-cells are produced from simple "blanks" in a kind of assembly line production. The identification of all possible cells and foreign substances requires an army of billions of scouts. For each T-cell can track down only one single substance with its receptors. That is why all possible variations are produced according to random principle, including many which cannot be used. The first test checks whether the T-cells recognize the features of other cells. Only if this is the case are the T-cells allowed to pass. The features which a T-cell recognizes determine its later function. Either a killer cell or a helper cell results, depending on whether a square or a circle fits. If a T-cell does not recognize any feature, it is useless and must be eliminated. The immune system works in principle like this robot. A signal forces the cell to commit suicide. This is how unusable cells are eliminated. T-cells are supposed to attack only foreign intruders which reveal themselves by particular antigens. It would be fatal if they also reacted to the body's own antigens and destroyed the body's own cells. That is why a second test is necessary. The body's own antigens are presented together with the tissue features. Only T-cells which do not react may begin their service in the immune system. The next case is different. The T-helper cell has recognized an antigen from the body. It is dangerous and must be destroyed. The rigorous process of sorting out T-cells which could damage the person's own body ensures that only cells remain which are specialized in recognizing foreign objects. Although important helpers in defending against pathogens, they make organ transplant more difficult. An organ transplant at the Medical School Hanover. This liver is the last hope for a patient whose own organ has been destroyed by cancer. The long-term success of a transplant depends on the selection of a suitable donor organ as well as other factors. The better the tissue properties of the recipient and donor match, the weaker the rejection: the organ offers fewer "attack targets" to the defence cells of the recipient and it is not destroyed so quickly. A series of tests which determines what tissue properties the organ has and which ones it doesn't have is therefore part of the preparation for every transplant procedure. The result is a profile of properties. It consists of combinations of letters and numbers. Specialists can read from this information if a donor organ has more compatible properties or if the incompatible properties are in the majority. All of the organ donations in Germany, Austria and the Benelux countries are reported to Eurotransplant. Here the organs are allocated to waiting patients who are also registered in the central database. An ideal donor organ is not always available. Prof. Pichlmayr: „There are particularly urgent situations for some sick people who need an organ very quickly if they are to survive or to become relatively healthy again. Under certain circumstances, you can't wait very long at all. Then you simply have to take the next possible organ offered, so to speak. When we think of acute liver failure, we need an organ within only a few days. Then you have to accept compromises with the tissue compatibility. And you cannot assume that there will be especially good compatibility for the majority of all patients. That is really quite rare, we people are all very different from one another, and we may have excellent compatibility in 10-15% of the cases, and in all other cases it will be less than that." Animated film (length: 1:44 min) If the tissue properties of the donor deviate strongly from those of the recipient, the transplant will be destroyed immediately by T-killer cells. They are programmed to attack the foreign targets. But rejection reactions can occur even if the tissue compatibility is better. Phagocytes present segments of the transplant as antigens. They are displayed with the tissue properties on the surface. If a matching T-helper cell comes along, it docks on and is activated. In a similar way a killer cell finds its landing space. A command from the helper cell activates the killer cell; it divides, and normally the search for transplanted cells begins then. Fortunately, the activation of the Tcells - the lymphocytes - can be repressed by medication, bringing the rejection to a halt. Prof. Pichlmayr: „The immune suppressives used today have a wide range of effects, we have a number which we can alternate. The most important are the Tlymphocytes which always bring about this cell interaction with the foreign tissue and can also destroy the tissue. So most of the immune suppressives are aimed at the T-lymphocytes. It has been observed that as time passes following the transplant we are fortunately able to reduce the immune suppressives, we need less repression. But a certain degree of repression of the immune system is always needed, and of course this entails risks, we become more susceptible to infections and, in particular, there is the danger that we will develop malignant tumours in our bodies years later because we obviously need similar defence mechanisms for this as well." For Andreas Hatopp, the medications mean an increase in quality of life. Patient: „As a transplant patient, you do not really have any physical restrictions. My hobby, for example, is sports, and I still do some athletics, I am a member of a club for people with organ transplants where I take part in national championship competitions and, every two years, international championship competitions. I also run, mainly the short and middle distances, I mean 100 and 400 metres, and have almost no physical restrictions in comparison with healthy people my own age. I can, if I train properly of course, perform just as well as anyone else." Patients who are not segregated as sick people, was far as possible live normal lifes, accept the foreign organ as if it were their own. Patient: „MYou only think about it when you have to go to the doctor's for a check-up every two months, then you just have to think about it because of the circumstances. Or, because of my profession, whenever I have to deal with people with kidney transplants or with dialysis patients, but in general, in everyday life, I hardly ever think about it. Since there haven't been any problems for 13 years, I don't waste any time thinking about it. Practically speaking, it's my organ." The question of organ donation touches the person's own death. Many push that thought out of their heads. Some fear that everything might not be over even when they are brain dead. It is hard for them to view a person whose organs - with the exception of the brain - are being artificially kept functioning as a dead person. Yet the diagnosis of brain death has been clearly regulated. Two experienced doctors who are not members of the transplant team must determine beyond any doubt that all brain functions have ceased. Prof. Pichlmayr: „All people must feel that they will be given the best possible treatment until they have died and that the doctors will not give up too quickly because they want the organs, that would be horrifying, and the second thing is that death has been determined as an absolute certainty. And death in this situation is the so-called brain death, the complete and irrevocable cessation of all brain functions. And I believe that we can all agree that when we don't have a brain, when we don't have any more brain functions, that we are then no longer the living people who we were. So that the failure of the entire brain can be regarded as the same as the death, the deceased nature of this person." The brain death of one person can mean new life for another. The number of people waiting who can be offered this chance is not only a question of medical progress. It requires the commitment of people who can think beyond their own deaths. Three people, handicapped to varying degrees. They all have the same disease: multiple sclerosis. The immune system does not attack foreign organs, as in the case of transplants, but rebels against its own body. Multiple sclerosis is one of the autoimmune diseases. The patients suffer from disruption of motor movements. There is not yet any method for fighting the causes, but the symptoms can be relieved. At the Augusta Hospital Anholt, movement therapy and medication is being used successfully to stop or at least slow down the progress of the disease. 120,000 people in Germany are affected by this disease of the central nervous system. Multiple sclerosis also causes changes in the brain. Cells of the defence system damage nerve paths which are important for control of motor movements. The destroyed areas can be seen on X-rays. Animated film (length: 0:58 min) In particular, certain T-cells attack the body's own tissue. Actually, only T-cells which do not recognize the body's own antigens should be allowed to leave the production area. These cells fit the triangular own antigen and should really be sorted out and destroyed. But this process does not proceed without error in the immune system. T-cells which can attack the body's own tissue enter circulation. But their destructive work does not begin until the self-reactive helper and killer cells are activated, such as is the case with infections. In the case of multiple sclerosis, viruses and bacteria which carry the same antigen as the nerve tissue for "camouflage" are considered to be the triggering causes. The T-cells then attack the nerve tissue as well, which ultimately leads to the typical symptoms of the disease. The autoimmune disease multiple sclerosis, for which genetic factors also play a role, cannot be cured. The patients must slowly learn to deal with everyday life in spite of their handicap. When Ute Küster goes to work in the morning, she normally senses if the day ahead will be full of pain or if she will be able to perform her duties reasonably free of problems. Ute Küster has chronic polyarthritis, a rheumatic illness which attacks the joints. Rheumatism is the general heading for painful illnesses of the movement structure. They are frequently caused by the body's own immune defences. About two percent of the population is affected. Ute Küster had to accept the fact that she could perform only light duties which did not require much effort. Most of her trouble comes from her wrists. Sometimes things can be done quite well, but the pain always returns at irregular intervals. Then every movement becomes torture. Rheumatism is wrongly regarded by many people as an illness of the elderly. Many parents are thus surprised when their child is diagnosed with rheumatic arthritis. The body's own immune system causes inflammation in the joints. As is the case with multiple sclerosis, experts suspect that earlier infections by viruses or bacteria are the cause. Some children have had German measles, others a throat infection or a gastro-intestinal illness caused by salmonella. The Children's Rheumatism Clinic in Garmisch-Partenkirchen specializes completely in young patients. Mothers remain with their children for the entire period of the treatment which lasts for several weeks. That is part of the therapy concept. Sandra Konrad studies business administration. She can walk thanks to the regular treatment in the Children's Clinic. However, the chronic arthritis has led to disruption of her growth. Patient: „At the age of six, I had the first attack, and my paediatrician sent me right to Garmisch-Partenkirchen, but the doctors believed that it had begun earlier, because I always had swollen knees when I was a small child and had never liked to walk. But today I do alright. There was a bad period, when I was about 14, 15, when I sometimes thought, why me, but that also passed with time. What has always bothered me was skiing in winter, I tried it once, but it wasn't really possible because of my joints, and I was always afraid of falling and breaking something, I tried playing tennis, but that put too much stress on my arms. Otherwise, I try virtually everything, including tours of cities, I can ride a bicycle anyway, and my friends keep my condition in mind and do activities which I can participate in." When children come down with rheumatism, it hits them at a time in their lifes in which the desire to move is especially strong. To reduce the pain, many children become used to making movements which are completely wrong and which accelerate the destruction of the joints. To prevent the poor posture from becoming permanent, the mothers learn exercises which they can perform with their children at home. Swimming is also an important part of a gentle movement therapy. Although some of the triggering factors for rheumatic illnesses are known, we still know very little about their causes. Although medication can alleviate the inflammation in the joints, there is still no therapy which would eliminate the causes. This is true for all autoimmune diseases, not only for rheumatism or multiple sclerosis. Research concentrates on new substances which are supposed to stop the immune defences from acting harmfully. But they are primarily experiments. The attack on the person's own body is the other side of the coin of the human defence system which otherwise protects us like an invisible bodyguard.