tirsdag den 24. maj 2011

Transplants and immunology

The immune system is the system that protects our body against foreign and often harmful organisms such as parasites, viruses, fungi and bacteria, yet it is not only microorganisms but also inorganic particles, as well as damaged cells and debris of broken cells is being fought. This is the to secure us against a variety of diseases and other invasions. Initially, our immune system ensures that the invading organism are controlled, but the longer the body is generating a resistance to the foreign invader - immunity. Itself immune divisions and mechanisms will be described later.

The way our immune system can recognize foreign organisms from the body's own happens according figure 1 by Th lymphocytes (T-helper) can recognize the structure of the proteins (antigens) which is the body's own vævsceller (and all other cells for that matter), and This recognition does not follow a reaction. Can Th does not recognize the antigen will be raised the alarm when the transplanted organ will be seen as an invading organism. The way this recognition, or lack of work is by different molecular complexes. The transplanted cells will have a random antigen (illustrated by a square box in the figure called MHC II) that will form a complex with Th-cell protein TCR and CD8, and with the new cell's own MHCI and antigen. Since this antigen and MHCI receptor would be foreign to the body, and Th, the new tissue will be classified as exotic and inherently pernicious (it would obviously be handy if the immune system could then distinguish the invasive organism was also harmful to body as a repulsion of bodies could be avoided, but so is our system is designed).

Problem b:

When the inserted organ / tissue initially not accepted by the body's own, a long chain of reactions begin that seeks to reject and destroy the inserted tissue / organ. First I would describe the various mechanisms of the immune system is composed. As mentioned earlier, our immune system is divided into different groups, which here follows:

· The outer defense

· An unspecific, innate defense

· A specific, dedicated defense

The first of the three defense mechanisms, the external passive defense, is irrelevant for this task to describe in more detail because it surgically have crossed this barrier, which otherwise consists of a variety of more or less impenetrable physical barriers, skin, mucous membranes, the formation adverse environments for invasive organisms such as this low pH or mucus. The organisms you yourself dietary intake is usually decomposed into the strong acid in the stomach, and should they survive the stomach mucous membrane covered with a thick layer of mucus, and they will also be attacked by various digestive enzymes.

The second category is the nonspecific defense, innate. This defense will always be the first real response to an invasion, and the system will be able to recognize foreign substances, as mentioned earlier in the task. If a microorganism or other yet to penetrate the passive defense and move into the body (intestinal tract do not count as part of the inner body (Endoderm) but as a part of the body's outer (ektoderm) the body's immediate reaction consist of a combat the intruder. This fight will take place primarily at the micro-organism will be included in endocytosis in a macrophage (phagocytic) and here the body will be disbanded could be described more precisely: Fusion with lysosomes ... ... Fighting can also be done by a number of processes in which micro-organism's surface is attacked by various substances from the immune system, for example, can be toxic to the microorganism or mark it as other parts of the immune system can recognize it and then kill it. A third way a foreign microorganism also can be destroyed using komplementærsystemet. In the body are a number of proteins involved in the eradication of microorganisms. Some of these proteins that constitute the "complement system", contained in blood plasma or on cell surface. Some of the proteins in the complement system is capable of producing protein channels in cell membranes of microorganisms. Through these channels which water flows into the microorganism due to the osmotic pressure, which therefore will perish / burst (when a cell bursting states with a nice word to the lyserer).

However, the main weapon phagocytic as actually there are three kinds of; neutrophils, macrophages and monocytes, but one is a development of the second:
The neutrophils are mainly in the blood from which they can quickly penetrate into the tissue infected by microorganisms,
Monocytes circulate in the blood from which they are able to migrate into infected tissue and develop into macrophages.
Macrophages, which are developed monocytes.

Microorganisms can be incorporated by both types of cells which will then move with lymph to the lymph nodes. The nonspecific defense is in itself not enough to combat alien invasions, but nevertheless plays an important part in the activation of the next level in the immune system, the specific defense

Some microorganisms, especially specific types of virus can prevent the nonspecific immune response. Most of these microorganisms hunted down by the learned, or specific immune response. Thus, it is also the case with prisoners bodies are not accepted by the body. Since these vævsceller will be seen as invasive, your body will react like the one every other intrusion. And this reaction will proceed in approximate order, as is described in Fig. 1:
Th, which is immune conductor, will detect the invading cells, and thereby activate macrophages and T-killer, and several other B and T lymphocytes.
Macrophage will, as far as possible to come to incorporate the new cells endocytotisk, and dissolve them, then will produce macrophage cell antigen on the membrane using MHCII-antigen complex.
T-killer will also attack the new cells. T-killer bear on TCR and CD8, which can form complex with MHCI (illustrated with a box of triangular inroads in) and antigen on the "infected" cell, which in this case is a cell in the inserted tissue (arrow from T-killer also illustrates this in Figure 1). T-killer will after the formation of MHC II, CD8, TCR complex inject a poison into the cell, this poison is composed of small enzyme-containing grains, and called granules, some of these forms holes in the cell membrane, which then goes to reason (see description of komplementærsystemet above).
Different microorganisms have their own special characteristics which certain cells in the immune system learns to recognize. When the body is infected with a microorganism, there will often be a symptom of this fight. In some cases, there will be illness in greater or lesser extent. During immune control of microorganism, the specific cells to produce antibodies immunoglobulins which can bind the micro-organism, together with other microorganisms, so that the macrophage can incorporate large groups of microorganisms at a time. Antibodies are produced by a certain type of white blood cells, B lymphocytes (plasma cells), which also is capable of eventually able to recognize a particular microorganism. Upon re-infection, these cells are B-cells remember quickly launch a vigorous production of antibodies. The immune system's ability to "remember" microorganisms are the basis for vaccination against infectious diseases. When the body's immune system has killed all the "invasive" cells from the implanted organ, the body will be dead, and the remains of the dead cells will also be dissolved by macro profession.

When we transplant tissue or organs, like as far as it is possible to find a donor whose cells, and thus genes are so closely related as possible. Therefore, a family often be preferable, since hereditary material will be related. When dealing with genotypes in the context of organ donation, it will be because the cellular membrane proteins that are expressed through the phenotype, would be important for recognition of cells as the recipient's own body in the above task.

As shown in Figure 2 is an illustration of a family with a mother, a father and four children. Genes for these proteins is illustrated here as being recessive and is co-dominance when all genes are described in lowercase letters: a, b, c and d. If we must assess where there will be more likely to tissues, it is in this specific cases among the children. There are illustrated four genes for tissue type, and parents share any of these, so will the kids could only have one gene from each parent, but a 25% chance of similarity with a sibling (as only can be formed four different configurations). However, there is also the risk that none of the genes are the same (for example, child with child ac bd), this risk is also at 25%, this is not the case with a transplant from the parents, where you always want to share a gene. However, one could imagine a situation with another parents:
Mother: a, c
Father: c, b

Possible offspring:
a, c
a, b (in this case the mother would be ideal as a donor)
c, c
c, b (in this case the father would be ideal as a donor)
It is illustrated in the case equally well to choose parents as donors.

As mentioned in the previous task, an attempt to find donors with the same tissue type, but since this is often difficult, it is possible with medical intervention, preventing the body to repel body. One of these substances can be medicated with cyclosporin is. This medication suppresses various functions in the immune system. The cyclosporin do is to curb the sharing of Th. by inhibiting the transcription of genes that control cell proliferation of Th. Ie after Th has been recorded the antigen and thus a recipe for the antibody, which it must pass to macrophages and T-killer cells (see Figure 1), this information may not be used much since the one cell which has the recipe is only effective if it can divide, so that activation is much faster. In other words, you go in and suppress the immune system where it is most important. Since Th is unable to activate the rest of the immune system, the new tissue will not be broken off as it has been explained in one of the above tasks.

Immediately, I do not believe that cyclosporin in the quantities being dosed is able to inhibit the immune system completely, as this would fatally, and could lead that they would die of the most common diseases, and this situation would remind a person infected with the HIV virus as HIV virus and AIDS also affects Th cell, so that the host would otherwise die of curable diseases like colds. If this was the case with cyclosporin consequences would be very unfortunate, I am therefore also assumed that the dose is minimal. Another problem of this type of medication is also that as soon as you stop it, your body will again trigger a repulsion of the transplanted organ, it is therefore necessary for lifelong medication.

You use too cyclosporine in combination with RA, which is a joint disease where the body's own cells are attacked by T-killer, braking, this disease is in the same way as when braking, the repulsion of a new body.

The immediate reaction by the use of cyclosporine may be an impaired immune system, and the further impact of this will be more frequent illness. Since the body's immune system is impaired, various microorganisms such as viruses and fungi easier to live in the body and attack their target cells, such as a cold virus that attacks the mucus-producing cells in the nose and throat region. This reaction would occur because Th is not specific to the repulsion of organ tissue, but against all invasive organisms.

The problem of organ donation is as mentioned previously that tissues often are too different, so that you have to medicate, with the side effects that come with the rest of the patient's life. One way to solve this problem would be if everyone had a single-edged twin brother or sister, but since it is very few who have it, this is not a real possibility. Yet there is another path, which is similar to the above proposal: stem cells. Stem cells are cells which are capable of developing into all tissues, and the special about stem cells is that they contain the exact same genetic material as a self. The idea is that you should take your own stem cells or umbilical cord blood, and keep this nedfrossent for possible organ donation should be made. Suppose a person x has been frozen stem cells down. He'll have an accident, and his liver is damaged heavily. This will then be able to introduce some healthy and fresh stem ix, and they will proliferate until the liver is restored. Immune system will not respond because the genes will be expressed with the same membrane proteins as the existing cells in the body (this is especially MHCI receptors that can recognize). In this way, x could be cured for a number of diseases and accidents, such as muscle injuries, injuries of the spine, brain damage, etc..

Now could we ask ourselves why there has been a much greater use of stem cells. But the reason for this is due to two things, I think: The first is always in the general population if a mistrust and skepticism of scientists and their findings (history has taught us that not everything has been developed by people in white coats are well the reason), and in addition, especially the Catholic Church, with its over 1 billion members, drawn heavily in handbrake [1], and condemned all dealing with stem cell research to do (it should also be mentioned that the other two major religions; Judaism and Islam have never had controversy with stem cell research). Their argument is that the ability to create life and take life is in God's hands, and it is not man's opinion, to change the will of God. Another problem with stem cell research is that previously these cells come from embryos (or more often from an embryo a) (a blastocyst in early, around 4-5 days, consisting of approximately 100-150 cells) which we will have to killing [2] and since the Catholic Church is against abortion, they are thus also against this form of stem cell research. Below I've listed the various arguments for and against stem cell research:

· Arguments against stem cell research (especially embryonic):

o A embryote is also life and if you do not share this view you can then say that a embryote is the precursor to life, which means that proposes life to death to save lives, and this vision can not be justified ethically.

o One should rather explore other areas of stem cell industry (such as by cells from the umbilical cord or from fat)

· Arguments for stem cell research

o If you look at it from a utilitarian [3] point of view, considering the usefulness of the researchers heaviest dish: the effect of stem cell research has been a far greater costs involved the removal of stem cells (also from embryos)

o An embryo is not the same as a human, it is not life itself but can only support life

o Roughly speaking one can say that the goal holier agent (a tougher version than the utilitarian point of view)

o Embryonic stem cells have proven to be more apt than stem cells from blood or adipose tissue (used as a counterargument against the idea of more research in this area)

Personally, I would say that we should look utilitarian on this matter, thus weighting the costs it will have to get done with stem cell transplantation is available and what benefits it will have. I believe that the benefits are far greater, and the idea of being able to cure life should not be a controversy in any religion. By contrast, I can partly agree with the argument that the use of embryos should be avoided (even when it is expected that it is a human being), I do not think that healing justifies killing of embryos for their own benefit. So if it's managed to isolate stem cells from adipose tissue, and if more research can make these stem cells are as good as embryonic stem cells, this is a very positive news.

Another, and more dark side of organ donation could be avoided by stem cell research is illegal organ transplantation: wealthy people who in less legal ways to purchase bodies from less affluent people, or in more serious cases, kill to get organs, is something of the most despicable taking place. Could we get this black market to life, it would be beneficial to all mankind.

[1] For example, the current U.S. President George W. Bush, who does not belong to the Catholic Church, introduced a bill in the U.S. that money from the state must not be used for stem cell research, which has been a major blow to stem cell research.

[2] However, there have been studies done where they have taken stem cells from a museembryon without killing it. (Researchers from Advanced Cell Technology of Worcester)

[3] Utilitarianism is a philosophical direction which believes that all actions must be judged by their usefulness