At the Rockefeller Institute have both kidneys removed the dog and one re-transplant. In most such cases the dogs are kept good health. The pathological examination of the kidneys showed that the kidneys are completely normal. Complete interruption of its circulation for a few minutes and sewing his blood vessels and ureter is not disrupted kidney function. With the surgical point of view, the transplant is possible.

Homotransplantation using the same technique has yielded the same results. In the first few days after surgery, the dogs who have undergone a kidney transplant obtained from another dog were in the same condition as dogs that have undergone autotransplantation.

After 6 or 7 days, the results are changed; kidneys were congested. After 25 or 30 days a large amount of albumin present in the urine, and is present even hematuria. After seven or eight months kidneys have become sclerotic. In many places there was infiltration of leukocytes. Carrel is thought that something triggers this loss, but it is not called the refusal. And it was less, not to use a modern term (3).

After homotransplantation thighs scalp or animal body reaction was not observed against the organ in most cases. In one case, the transplant scalp and ear and in two cases transplantation legs, limb is not swollen, and after 20 days the new parts were in such a state that could not believe that they are not original (acquired by birth). The explanation of this phenomenon is that it was almost certainly the HLA (human lymphocyte antigen), to which it was not then known

EARLY PERIOD TRADE BODIES

Alexis Carrel in the International Surgical Association is already predicted (1914 g.) To the surgical side of organ transplants was "complete". Thus it was possible to perform organ transplants extraordinary ease and with excellent results from the anatomical point of view. However, these methods could not be used in human surgery because homotransplantacije almost always have been unsuccessful because of the possibility of organ rejection after transplantation.

Alexis Carrel first noted that anastomosis of blood vessels runs large vascularized organs such as the kidneys in the same animal, or from one animal to another. The simple method of vascular anastomosis using fine needles and thread was used since 1902, with some modifications (4). This requires careful dissection, accurate identification of several layers of blood vessels to connect, control bleeding from both ends, and Securing courts together so that posuvrati intimacy. Other authors in Europe and North America were carried out similar operations in the period 1900th-1930th years. In almost all experiments were used kidneys because of its simple vascularization and the presence of the ureter, which gives the index function within a few minutes due to the fact that this is the body that comes in pairs, allowing the survival of the animals in case the transplant fails.

Alexis Carrel (1873 - 1944)

Nobel Prize winner

for medicine in 1912

. Historical Perspectives on Relevance Immunology

       transplant

It is generally accepted that the early work of scientists in the field of behavioral Medawar allo-transplant skin gene in laboratory rabbits, first published in the period 1944th-1946th, marked the formal beginning of modern transplantation period. The historical background of the time domain bears special relevance to our topic. Most of incentives to early research ventures in the field of transplant originated in the war-torn Great Britain in the 1940s, during the intensive efforts of the British and surgeons volunteers from other countries to treat and rehabilitate the pilots of Royal Air Force who were injured and mutilated during the legendary fighting for UK. One of the members of the volunteer surgical team, the late John Marquis Converse, worked closely with Sir. Harold Gillies employee in center for plastic surgery Park Prewett Hospital in Basingstoke, Hampshire.

During one of the many Converse's surgical operation, in the process of transplanting skin of a RAF pilot, Sir Harold is brought into the operating room, a tall, skinny, young zoologist from Oxford University and said, "Doctor Medawar is interested in the problem homograft. This declaration marked the beginning of a long friendship between Converse and Medawar, after talks in which the Medawar expressed special interest in the behavior of skin homograft and to process their rejection. During the discussion, it has been hypothesized that in case if the epidermis, which in itself has no blood vessels, could be separated from the vascular dermis, epidermis then it could survive as a free graft. Converse gave a piece of skin Medawar, who returned to the lab and divide the epidermis from the dermis using raw-unsophisticated preparation Trypsin, which is in itself contained an enzyme elastase. The resulting leaf epidermis was placed on the patient granulation surface wounds, but he was gone by tomorrow.

This was Medawarovo first exposure to transpantiranju skin in humans, and this has led to its collaborative efforts with respected British plastic surgeon, Dr. Tom Gibson, with whom he Medawar published a classic study on human subjects. This experience has also marked the beginning of Medawarovog systematic experimental study of skin grafts rabbit, which has produced a basic foundation for the role of immunology in rejecting allografts. Converse enduring fascination with the field of transplantation is very intensified its work in Basingstoke-in. After his return to civilian life in 1948, he established one of the first America transplantation research laboratory at Bellevue Hospital in New York, and there was soon attracted a talented team of associates. (5)

Converse has early realized the need for frequent exchange of ideas between the then small society of doctors and biologists all over the world who have an interest in transplantation. Converse attended the conference, researcher in 1951, at a conference in Arden home, which was attended by the now legendary names as: TS Hauschka, D. M. Hume, N.Kaliss, C.C. Little, W. Longmire, R.E. Maumenee, PB Medawar and among others GD Snell. This meeting was initiated Conversa to seek ways and means to establish regular channels of exchange between the members of this new scientific discipline.

Converse has assured members of the Academy of Sciences of New York to sponsor a series "of International Conference on transplant" in order to provide the focal point for meetings in the various disciplines that were beginning to enter the field of transplantation. The first International Conference in the series, called "The attitude of Immunology at Homo tissue transplantation", held in New York in 1954. This name was not accidental; one of Conversovih most significant achievements during the year was the direct involvement of professional immunologists in transplantation.

Converse was convinced that the immunological approach was crucial to allow progress in our understanding allograftske reactivity.

Upon arrival at Bellevue Hospital in 1948, Converse has spent years trying to incorporate leading immunologists New York City, especially with the Rockefeller Institute of New York University, who had connections with the transplant. Unfortunately, during this period classical immunologists are looking to transplant with a touch of suspicion. Something in the spirit of a short memoir called "peripatetic school (Peripatetics) immune Surgeon," which was presented at the Fifth International Congress of the Association of transplantation, 1974:

"I remember well how we pray immunologists to attend to the early conferences. One immunologist visionary, Rueben L. Kahn, he finally agreed to come on the first Konferenciju- and scientific field called immunology is now a senior member of the club. The irony in all, in fact, that indicates that the transplant research then quickly sparked a renaissance-boom in the field of immunology orthodox ... "

The huge success of the conference on the "Attitudes Immunology with Homotransplantacijom Tissues" has begun to attract a growing number of prominent immunologist world-class on 6-th row transplant conference, sponsored by the New York-ery Academy of Sciences in the period 1956th-1966th Converse was chaired and organized by each of these meetings. He also collected the funds necessary to finance the costs of the conference and travel costs of experts. Issued "The conclusions of this conference," constitute a unique historical document, in which every modern principle of transplantation biology and medicine was presented and discussed, in a joint forum of general scientists and medical professionals (clinicians).

Exceptional is the fact that almost every central concept or hypothesis which supports our current efforts in the field of transplantation was first formulated in one of the above conferences. One early additional product of the First Conference of the New York Academy of Sciences, was the first successful kidney transplant, 10 months later (December 23, 1954), cond

This event, as well as the pioneering research of kidney transplantation, scientists Hamburger and his group of scientists Hume's, Merrill and their colleagues, produced early evidence of clinical relevance transplantation, and as such, gave a strong impetus for further research. The resulting rapid growth in this field has stimulated the creation of the Transplantation Society during the final session of 7-Me International Transplantation Conference, New York-ery Academy of Sciences, 1966-year. As noted by Sir Michael's Woodruff, a 1975-this year, scientist John Marquis Converse was one of the true fathers osnivajućih the Transplantation Society. His influence, rather than the influence of any other scientist, has led to the creation of this society.

From its relatively modest beginnings, immunology has now assumed a fundamental role in the field of transplantation, and as such was responsible for accelerated progress to basic science and science at the clinical level. On the other hand, transplantation research has revolutionized orthodox Immunology. Such concepts as the resulting immune tolerance and the role of MHC in immune reactivity, for example, a direct result of cross-fertilization. Of particular importance at the present time would be to record this connection, when so many new disciplines, and especially molecular biology, entering the field of transplantation. It is safe to predict that each of these disciplines derive immense benefits from the challenges produced by transplantation.

One of the most relevant products relations immunology and transplantation was the discovery of the role of MHC (HLA in man), as the main qualifier immunoreactivity. History and development of HLA give a clear illustration of the extent of inter-disciplinary work and enthusiasm, who was such an integral part of the progress in the field of transplantation, from the birth of the modern era, 1944. We now propose to focus on the early beginnings and geometric explosion of knowledge that followed in the field, which is generally known as the "tissue typing a", as the prototype of involvement in immunology transplantation (7).

strong incentive for further research. The resulting rapid growth in this field has stimulated the creation of the Transplantation Society during the final session of 7-Me International Transplantation Conference, New York-ery Academy of Sciences, 1966-year. As noted by Sir Michael's Woodruff, a 1975-this year, scientist John Marquis Converse was one of the true fathers osnivajućih the Transplantation Society. His influence, rather than the influence of any other scientist, has led to the creation of this society.

From its relatively modest beginnings, immunology has now assumed a fundamental role in the field of transplantation, and as such was responsible for accelerated progress to basic science and science at the clinical level. On the other hand, transplantation research has revolutionized orthodox Immunology. Such concepts as the resulting immune tolerance and the role of MHC in immune reactivity, for example, a direct result of cross-fertilization. Of particular importance at the present time would be to record this connection, when so many new disciplines, and especially molecular biology, entering the field of transplantation. It is safe to predict that each of these disciplines derive immense benefits from the challenges produced by transplantation.

One of the most relevant products relations immunology and transplantation was the discovery of the role of MHC (HLA in man), as the main qualifier immunoreactivity. History and development of HLA give a clear illustration of the extent of inter-disciplinary work and enthusiasm, who was such an integral part of the progress in the field of transplantation, from the birth of the modern era, 1944. We now propose to focus on the early beginnings and geometric explosion of knowledge that followed in the field, which is generally known as the "tissue typing a", as the prototype of involvement in immunology transplantation (7).

lolō

Definicije riječi ili izraza lo

uzvik

used to draw attention to an interesting or amazing event.

and lo, the star, which they saw in the east, went before them

stimulate the creation of the Transplantation Society during the final session of 7-Me International Transplantation Conference, New York-ery Academy of Sciences, 1966-year. As noted by Sir Michael's Woodruff, a 1975-this year, scientist John Marquis Converse was one of the true fathers osnivajućih the Transplantation Society. His influence, rather than the influence of any other scientist, has led to the creation of this society.

From its relatively modest beginnings, immunology has now assumed a fundamental role in the field of transplantation, and as such was responsible for accelerated progress to basic science and science at the clinical level. On the other hand, transplantation research has revolutionized orthodox Immunology. Such concepts as the resulting immune tolerance and the role of MHC in immune reactivity, for example, a direct result of cross-fertilization. Of particular importance at the present time would be to record this connection, when so many new disciplines, and especially molecular biology, entering the field of transplantation. It is safe to predict that each of these disciplines derive immense benefits from the challenges produced by transplantation.

One of the most relevant products relations immunology and transplantation was the discovery of the role of MHC (HLA in man), as the main qualifier immunoreactivity. History and development of HLA give a clear illustration of the extent of inter-disciplinary work and enthusiasm, who was such an integral part of the progress in the field of transplantation, from the birth of the modern era, 1944. We now propose to focus on the early beginnings and geometric explosion of knowledge that followed in the field, which is generally known as the "tissue typing a", as the prototype of involvement in immunology transplantation (7).

The commitment and enthusiasm of these volunteers was one of the most important and the most striking aspects of this project. It is important to note that many key scientific advances in our understanding of the major histocompatibility complex in humans (HLA), which were the direct product of the coordinated use of experimental skin grafts in vivo, achieved sacrifice of well-meaning donors and recipients. This gave a definitive test of the validity of compatible data derived in vitro serological and cellular techniques. These early steps consisted of a skin graft in the recipients selected based on relatively coarse serological criteria were related to the recipient  donor-leucocyte group compatibility.

The same technique was then applied to study the role of newly discovered leukocyte antigens, which defined the speed and intensity alograftnih rejection. This was followed by testing the activity of the Van Rood and Dausset 4a4b system's MAC antigens pre-immunized recipients. The product that crystallized out was test action of the leukocyte antigen in vivo. As a result of these systematic skin graft experiments, the role of HLA antigens in transplantation has been precisely defined by the more than 200 million family volunteers, including more than 600 persons (17).

Skin grafts were performed under conditions of different genetic code unutarfamilijarne provider-recipient HLA compatibility, and thus found a definitive experimental evidence for the role of HLA antigen of the transplant product. These studies have received recognition because they set a base for immunogenic "laws transplant" in human!

Thank you very much to exposed to your esteemed opinion!

With great Satisfaction with'll see you file you sent me!

Greetings from Sarajevo

Jasenko

Good point. Which other efforts and researchs could  clinical immunology do to contribute to the process of transplantion exept immunosupression and folowing its effects?

Thank you for your interesting question, my answer would be:

should be very near the development of immunosuppression, lot of effort and research in front of HLA tissue and improve diagnosis better match the donor and recipient, the molecular and genetic level, reduce the potential for immune-biological barrier better coincidence loss and reduced linearly quantified number of cytotoxic antibodies, that are a big risk for graft rejection transplant, especially in front of tipizacion and the early stage of transplantation ...., also improve precision and expand the range of clinical and immunological tests.

Improve also ,  early screening markers for early detection of early stages of rejection, to affirm and improve donor network in the sense of the affirmative influence to increase the number of donors, in particular the cadaver transplantation   and thus broaden the basis and greater number of potential donors and their better chances to find more compatible donors thereby proportionately reducing the risk of immunological rejection of reason, life , extend the shelf life graft id event was lower doses of immunosuppressive drugs or reduce their side effects ....!

Once again thank you for the successful cooperation ...!

Such a good point Professor. Could you keep us posted how to overcome immunological barriers in organ transplantation?swer

Thank you for your interesting question, my answer would be:

should be very near the development of immunosuppression, lot of effort and research in front of HLA tissue and improve diagnosis better match the donor and recipient, the molecular and genetic level, reduce the potential for immune-biological barrier better coincidence loss and reduced linearly quantified number of cytotoxic antibodies, that are a big risk for graft rejection transplant, especially in front of tipizacion and the early stage of transplantation ...., also improve precision and expand the range of clinical and immunological tests.

Improve also ,  early screening markers for early detection of early stages of rejection, to affirm and improve donor network in the sense of the affirmative influence to increase the number of donors, in particular the cadaver transplantation   and thus broaden the basis and greater number of potential donors and their better chances to find more compatible donors thereby proportionately reducing the risk of immunological rejection of reason, life , extend the shelf life graft id event was lower doses of immunosuppressive drugs or reduce their side effects ....!

Once again thank you for the successful cooperation ...!

This is excellent project in transplantation of organs, which I will gladly follow and be part in the discussion of.

Thanks a lot for nice words for my project I  am very proud  for that!

CONCEPT transplant rejection

Soon it was realized that the process is quite different from a heart attack, then the avascular necrosis, infection or inflammation, a loss of organ transplant. The term "refusal" is meant a process in which new host refuses to provide the "right of residence" organ transplantation Emile Holman, a surgeon at Johns Hopkins Inst. In Baltimore, took the 1920 transplant skin from mother to child with severe burns.

When a few days later, the transplanted skin more on the child, the child not only rejected the mother's skin, but has received strong necrotizing inflammation of your skin. This suggests that the antigens and the development of autoimmune diseases cause necrotizing dermatitis.

Holman noted significant implications of this experiment, but could not continue with the experiment (9). In 1951, David Hume in the Peter Bent Bnigham Hospital in Boston has started kidney transplantation from one person to another, using the thigh as a place of receipt. Experiments have shown that the kidneys were in operation for some time (when the transplanted kidney discarded), later to prevent renal transplant rejection (10). One of the most important aspects of this study is the need for cooperation more discipline, surgery, pathology, radiology and immunology, mutually respecting participation of each of them.

SECONDARY RESPONSE

According to the literature the British Council for Medical Research still in the period of World War II, the center of gravity is thrown at the problem of transplantation of skin. They asked Dr. Peter Brian Medawera to work with the plastic surgeon, Mr Thomas Gibson in Glasgow, on a leather transplant man, if possible, to investigate the use of skin of other providers. Dr Medawer soon noticed that he could rely on standard laboratory tests. If the first skin transplant placed with animals A to B an animal, she lived about 7 days.

If the second set of skin made the same way with the same two animals, a second set of skin is rejected in half the time. This so called "response to the second set of" (11). Its historical importance in the science of transplantation, histocompatibility and imunogenetici is very large. Dr Medawer has elucidated many aspects of immunology tissue using "replies the second set." He later won the Nobel Prize and a knighthood.

Medawar, PB (1915th to 1987th),

creator of transplantation immunology,

Nobel Prize for Medicine in 1960

Clinical immunosuppression

Since 1962 all tissue transplantation between individuals who are not related are performed on patients under the influence of chemical agents to suppress the immune response of the patient to the transplant. Many scientists have studied irradiation of the whole body as a means of immunosuppression, irradiation of the whole seedlings, and the use of drugs such as nitrogen mustard (nitrogen mustard). The breakthrough was made when Schwartz and Dameshek with Tufts University worked on the action of 6-mercaptopurine on xenogenic protein solution (12). They used a laboratory model in which the antigen was bovine serum albumin or human administered rat or hamster. Radioactive labeling of albumin, it is possible to follow the curve of his disappearance. Without immunosuppression, it is very may disappear from the circulation, by means of circulation of antibodies, or when the animal is administered 6-mercaptopurine, foreign protein had a normal disintegration time in body fluids of the recipient. Mr. Roy Calne was then a young surgeon who was doing graduate work in London. He applied the sixth mercaptopurine on kidney - transplant.

During the weeks of observation, it was obvious that he started a completely new era in experimental kidney transplantation. Wanting to work on this further and achieve cooperation with other researchers on this issue, Mr. Calne went to the United States. He worked with Murray and his group at the Peter Bent Brigham Hospital and Harvard Medical School. He soon found the sixth derivative of mercaptopurine, which is called Imuran (azathioprine). Results with Imuran were better than the sixth mercaptopurine; toxicity is lower, a longer duration of graft failure in dogs, it has become the norm. Among the first patients who were operated with immunosuppressive chemotherapy, was a patient whose postoperative course, in April 1962, went without a hitch, and that is more long-lived (13). Between 1965 and 1975, kidney transplantation is largely escaped the practice of the treatment of renal diseases.

Tissue typing

Discovery tissue typing is present in the works of Professor Dausset in Paris (14). He showed that human cells have characteristic antigens identified as HLA. Finding the type of tissue donors and recipients allowed the understanding of how the two

relatives, two brothers, or parent and child really related, or how many are antigenically similar to two people who are not related. Later it was recognized that these antigens typed tissues have specific locations in the genome.

HLA locus is on chromosome 6 and is divided into several regions and sub-regions. The molecules encoded by HLA-A, B and C region genes are called "class I molecules" are present in all cells, the Sail. In contrast to this, the encoded molecule, the HLA-D region gene (including HLA-DP, -DQ and -DR subregions) are called "class II molecules" are present on B cells, macrophages and dendritic reticular cells, and under the same circumstances, on intestinal epithelial cells and other types of cells. Combining, in particular HLA-A, -B, and -DR, and seems to correlate with a successful graft. In 8000 more than the first-cadaver transplant, very well combined planted DR and HLA-B (incompatibility antigen) had 20% graft survival better than threads combined transplants

Workshops on HLA histocompatibility

It is noteworthy that the early studies of HLA performed independently of the long-term studies in murine H2 system, which started in 1936 scientists Gorer, Snell and many others. Appeared to be no direct analogy between the H2 and the HLA antigens as they were defined H2 erythrocyte agglutination technique, while it seems that HLA antibodies was recognized only on leukocytes. One of Snell's students, Amos, was already discovered H2 antigens on the surface of mouse leukocyte 1953. After the realization of the need to coordinate efforts HLA research laboratories worldwide, Amos has initiated the first of a series of historical international histocompatibility meetings, this was their chairman organizer in Durham, the North Carolina, in 1964.

Stimulated by this fruitful meetings, a growing number of researchers joined the early pioneers, representational wide variety of disciplines. It is important to emphasize that even surgeons join these efforts. Clinical transplantation of kidneys began to make their first fragile steps, and it has made a major motivating incentive to support HLA research. In rapid succession of events, methods have been developed that are currently used for histocompatibility studies of lymphocytes, and those included limfocitotoksičnost (Terasaki scientist), and mixed lymphocyte culture (MLC). In the years limfocitotoksičnost and MLC remained the gold standard in histocompatibility studies in humans. The next stage is to wait for the birth of molecular biology techniques, which is currently rapidly gaining in significance.

In retrospect, it is of interest to point out that researchers were pioneers discouraged relatively daunting initial results. At the First International Meeting of 1964, serological techniques are then used did not show a serious correlation between the results obtained by different groups in the same cells. Nevertheless, the scheduled second international meeting, and it was chaired by a scientist Van Rood, in the city of Leiden, 1965.

Workshops on HLA histocompatibility

This became the theme for the Third International Meeting was held under the auspices of scientists Ceppellini-I in Turin, Italy, in 1967. At this meeting, blood samples were taken early in the morning from a local Italian family and they were forwarded to each of the teams surađivačkih blind system, with daily results of blending that were available in the evening. Each team tested samples of cells their techniques serum and reagents. Finally, Ceppellini presented the synthesis of the work of the whole group, which showed clear evidence of the existence mostly as a result of progress in the techniques that were used (lymphocyte-toxicity), a clear link was demonstrated between the results obtained by different groups after testing the same cell samples. MAC antigen, looks the same as the antigen LA2 Paine and Bodmer times, a similar parallelism is seen between antigen PLCrlyB1 Shulman and 8A antigen Van Rood times. Several new antigens were defined and their role in transplantation is documented studies of skin transplanted in recipients who have received specific procedures sensitivity with a group-specific leukocytes.

In this time it was not clear whether the leukocyte antigens were products of one genetic system, as proposed by scientists Dausset and Ivanyi, who called it a Hu-1 system, the MAC as the first product of that system or that it actually was 2 separate systems, including LA1, LA2 system Paine and Bodmer and 4a4b system Van Rood's. Scientists have agreed to this only one main large leukocyte antigen. The main role of the ABO antigens as potent alloantigen is also demonstrated clear conclusions in this period.

Directly relevant to the issue of the role histocompatibility factor in clinical transplantation, also has been shown to have the best long-term results of kidney transplants took place between HLA-identical twins, while transplants from HLA-identical twins full gave the worst results. The grafts from the donor family who were HLA haplogroup identical with recipients gave intermediate results.

Despite the fact that these studies were limited to the first two antigens HLA series, for example class I antigens, the data gave clear evidence crucial importance of HLA in transplantation. Various international organizations have been created as a result of these efforts, to promote the exchange and the division of authority, first in Europe (France Transplant, Euro and Scandia Transplant), and then in America (SEOPF, UNOS).

Since at that time only a limited number of reagents was available, it was not surprising that a very high correlation could not be detected for HLA kompatibilitet the survival of kidneys obtained from non-family related donor or (cadaver). This problem has created a division between the "true followers", who were mostly immunologists, and the so-called "non-believers in HLA", who were mostly clinical surgeons. This intriguing overview of human nature is that this conflict exists even today, nearly 30 years later!

After the Third International Meeting, transplant immunologists have continued to seek improvements in the accuracy of their methods and to establish and recognize even previously unknown HLA antigens. The results culminated in the Fourth International Meeting, held in Los Angeles in 1970 under the presidency of scientists Terasaki's. This meeting is the first proposed the existence of a third allele HLA series products, HLA-C. Following the Fifth International Meeting held in Evian in France, two years later, under Dausset's auspices, and given the unique valuable analysis of the global anthropological data on the relative incidence of HLA antigens in different populations around the world

Data are presented from several high adventure expeditions completion of various tissue-typing teams. Albert (Munich, Germany), is described antigens in Nepal; Degos (Paris, France), was traveling in the desert, and lived with the Tuareg for the same purpose. The American Indians, Pygmies, Polynesians, Eskimos, Tibetans and population of monkeys chimpanzees were compared with each other. Although this study was done with sera that recognize self-antigens class I, the results have provided valuable information with regard to the relative genetic relationships and the distribution of HLA antigens in different populations, giving a unique opportunity to trace the history of human migration in prehistoric times.

This era is also characterized by observing the associations between certain HLA antigens and the human disease; as Dausset was originally suggested. The first hard finding the correlation between the HLA and psoriasis, which is released Terasaki 1972, regardless of the report-Bewerton between HLA-B27 and ankylosing spondylitis, 1972. These findings have initiated intensive search for additional associations between HLA and disease. At least 50 diseases are now identified, which have some association with one or more HLA antigens.

After World War II, Kolff gave his machine in several countries and institutions to further experimental work. George Thorn, at Harvard University, is credited as dialysis has become standard therapy in the USA. dialysis is

possible view of the kidneys from a new angle, enabled a better understanding of kidney disease!

Great comments. Thew were were very useful to me and I learned a lot from them. Keep up the good work. Dr. Oggi. 

Thanks a lot for nice words and  good cooperation!

Since you are exprert in this field could you share who is your role mode in transplantation?

There were a lot of really rich history of clinical (transplantation) immunology .... but I think the key figure was in history was famous profesor Medawar, PB (1915th to 1987th), creator of transplantation immunology,

Nobel Prize for Medicine in 1960 Years!

Thank you Professor Karamehic for you answer

Thank you for your opinion and answer that is very well founded! Also thank you for the sent messages I opened and read with great pleasure (I was not able to open the first attachment, I do not know why)! These problems will be because, as much as useful immunosuppressive therapy for preserving the transplants, so much unfortunately must be deregulated selectively by our immune system and many negative consequences for our organism are created!

Perhaps it is better to invest more effort in the science of testing and the creation of artificial artificial organs, thus avoiding immunological-biological barriers and their response!

Thanks a lot for your favour!

Answer dr.Kou Hayakawa · :

I thank you for excellent articles, which I read with great pleasure and I must say and admit that you are dealing with the true original science and research!

Regards from Sarajevo

Jasenko

That you are really high-sophisticated and, of course, that patients doctors will have many benefits in the future from your research in science, which I thank you in advance!

What is your oppinion about artificial organ in transplantation?

An excellent question, because it is necessary to explore everything that would circumvent the immunological-biological barriers, this is in any case a redesigned artificial organ!

Thank you for your successful cooperation!

Excellent topic professor

Thanks a lot dr.Nejra !

TYPES OF REJECTION TRANSPLANTS ORGANS

1.1 INTRODUCTION

Transplantation Immunology refers to a large number of events occurring after the alograft or xenograft is removed from the donor and transplanted into the recipient. There is damage to tissue both graft and tissue at the site of transplantation. The inflammatory reaction occurs immediately, and the immune response is initiated.

Transplants can be carried out in a wide range of genetic inequalities, ranging from auto-isograft to allo / xenograft. Clinically, with the exception of transplantation between monozygotic twins, donor organ and recipient will inevitably differ in one or more genetic loci, some of which may be identified as foreign.

Class II and Class II clusters of the large complexity of MHC histocompatibility due to their large polymorphisms in the species are the greatest problem in this area. Although differences in the smallest locus can also produce an immune response, which is partly a problem with bone marrow transplantation.

  Autograft / Autologic Graft: Transplantation of one individual's tissue from one place to another.

Isograft / Synergic or Isogenous Graft: Transplantation of tissues between genetically identical individuals eg cadaveric transplantation between monozygotic twins.

Alograft / Halogen graft: Transplantation between genetically different members of the same species, eg cadaveric transplantation between unrelated individuals.

Xenograft: Transplants between members of different species, eg from monkeys to humans.

Receptors previously sensitized to the donor graft antigen showed hyperacid rejection of the transplant, due to the presence of antibodies formed in the circulation. A cross-examination test, routinely performed prior to clinical transplantation, detects such antibodies.

In the case of a test positive transplantation is not performed. Despite the use of strong immunosuppressive drugs such as Ciclosporin and FK506, many patients find the episodes of acute clinical rejection, shortly after transplantation.

Such episodes are usually reversible, which is assisted by increased doses of conventional drugs or by adding antibody therapies, but will inevitably cause a certain level of graft damage. This damage can contribute to long-term degeneration or chronic graft rejection. Judging by this, it is clear that all types of rejection are associated with the immune response to donor antigens.

ACTIVATION OF IMMUNITY SYSTEM

Invasion of the body by any foreign material leads to a series of events that result in its ejection. Generally, these events include non-specific inflammatory and antigen-specific immune responses. Both responses are largely guided by bone marrow leukocytes.

Specific immune responses were mediated by T cells derived from thymus and antibodies by producing B cells. T lymphocyte is a leader in immune response, once activated by antigen, induces differentiation and activation of many other cells. The immune response is supported by many cells including macrophages, polymorphonuclear cells, NK cells and can be activated under the influence of simple trauma. Graft rejection is primarily an antigen-specific immune response to the body, but is also undoubtedly contributed to and augmented by an inflammatory response.

ACTION ACTIVATION

 Antigen presentation

T cells do not recognize free native antigens, but recognize short peptides composed of only a few amino acids separated from the protein (1,2,3). These peptides are linked to the principal molecular tissue complexity molecule (MHC) on the antigen presenting cells (APCs) and then transported to the cell surface and introduced to the T cells.

Generally, T cells carrying CD4 or CD8 superficial cell proteins can recognize antigen within MHC Class II and MHC Class I Proteins. In the developmental period of lymphocytes, their positive and negative selection results. Nephritic lymphocytes are selected based on the ability to recognize the MHC molecule of the host or its own, referred to as a positive selection.

Those T or B lymphocytes that have high affinity to their own antigens are eliminated, due to the risk of their further reactions against their own antigens, which is called negative selection (4.5).

Recent experiments have shown that CD4 8 + thymocytes represent critical phases in the development of T lymphocytes. These cells are cleaved when the receptor binds to the MHC molecule and the specific peptide present in the bone marrow cells. Different tolerances erase CD4 + 8 + timocytes early or later during their life and negative selection may occur before positive. The specificity of T cell receptor antibodies for both class I or II class of timed MHC molecules determines the CD4-8 + and CD4 + 8 mature T cell phenotype.

 The ability of mature T cells to react to foreign peptides as a priority of their own MHC is referred to as MHC restriction (6).

There are two possible ways in which the immune system can recognize aloantigenes, either directly or indirectly. In direct aloprene detection, T cells recognize the allylated MHC molecules shown on the APC itself.

Direct recognition is only possible if the cell itself contains antigen presenting cells (APCs), such as dendritic cells. Dendritic cells carrying MHC Class I and Class II antigens are assumed to be potent and specialized T cell stimuli (7). After transplantation, these cells rapidly migrate from the graft to the lymphatic tissue of the host, where they can recognize the host T cells (8, 9).

Traveling leukocytes with dendritic cell characteristics are present in most tissues. Most other cells within the graft, with the exception of endothelial cells, only express MHC I antigen and, as such, are most likely to have no major significance in activating the immune response.

The exact role of the endothelium in activating the primary immune response remains controversial. In cell culture, in the absence of dendritic cells, isolated endothelial cells are able to stimulate both CD4 and CD8 cells, giving arguments that support their importance in stimulation of the immune system (10, 11). Direct recognition stimulates the development of aloreactive T cells, which recognize and attack cell death cells.

If the spade does not contain its APCs, indirect recognition occurs. Apparently, it is possible to immunize the animal by rapid excretion, using peptide alo-MHC (12) proteins and recipient APCs, which asks to break the donor MHC (13, 14).

Indirect recognition of the aloantigen occurs when the halide halide MHC molecules are taken and processed by the APC recipient (15). Which is the true role of one, and which other way of presentation is not yet clarified. It is presumed that the direct route is most important for acute rejection, and the indirect path has a greater role in chronic rejection.

Other conditions for T cell activation

The primary condition for T cell activation is binding of its antigen specific receptor, the T cell receptor (TCR) to the peptide contained in the MHC protein. The TCR contains two similar chains, alpha and beta lanes, which with several chains make up the CD3 compleks. The TCR carries the specificity of the antigen / MHC binding until the CD3 complex transmits the activation signal to the T cell. With the signal transmitted via the TCR, the T cell requires one or more additional signals transmitted by direct interaction with the APC surface.

Without these signals, not only is the activation incomplete, but the T cells become non-reactive to future antigen stimulation, a condition commonly referred to as an angiogenic (16).

As the T cells are the leader in the immune response, the anergy of these cells would essentially be the desired condition in the transplant. Because of this, many experimental protocols are turned towards bringing T cells into an angiogenic state in vivo. There are many superficial cellular T cell proteins that potentially contribute to its activation. CD4 and CD8 proteins work by binding to Class I and Class II at APC.

Both CD4 and CD8 are associated with intracellular proteins such as P56lcK involved in T cell signal transmission (17). Additional T cell surface proteins such as CD54, CD2, CD11a, CD18 and CD5 act to increase the affinity of interaction between T cells and APCs, and can transmit further signals to T cells. One interaction that is presumed to be important for the T cell is transmitted through CD28 and CTLA-4 via linkage to one of the B7 family of proteins at APC (18).

CD28 / CTLA-4 on T cell initiates signal transmission process through T cell receptor resulting in increased cytokine mRNA transcriptionality and stability (19.20). Of importance to transplantation immunology is that this signal is transmitted through CD28 / CTLA-4 insensitive to inhibitory effects of cyclosporin, resulting in cyclosporine-resistant cytokine expression (21).

In addition to a large number of cell-cell-level interactions, T cells also receive important signals via their soluble proteins, cytokines, specific surface cytokine receptors.

The entire cytokine cascade was produced to increase both, immune and inflammatory responses. Of particular importance for regulating the transplant response is that these cytokines not only regulate the size but also the nature of the immune response.

Following the activation of the immune response, T cells have the capacity to produce a wide range of cytokines, of which IL-2 is of the utmost importance. After antigen stimulation and costimulators, naïve assistive T cells can be differentiated by TH1 and TH2 (Figure 4) (22,23) under the influence of cytokines.

TH1 cells through the cytokines they produce tend to be cellular responses, although IL-2 and IFN-γ can also serve for proliferation and differentiation of B cells, while TH2 cells direct the immune system to an antibody-dominant response.

Significantly, these two cell populations have reciprocal inhibitory activity, through the production of specific cytokines, IFN-γ and IL-10 inhibiting the proliferation of TH1 and TH2 cells.

There are thoughts that the immune system will try to move away from TH1 cells and TH2 cells, which would be perfect in the domain of transplantation, as acute rejection under the dominance of cellular mechanisms.

However, it is clear that besides cellular mechanisms in the process of rejecting grafts may be involved humoral mechanisms, where the response of TH2 cells would not be of greater value.

Measurements and manipulations of cytokines have lately generated a huge amount of interest (24,25,26). All proteins, either cell surface or soluble, that relate to T cell activation, attract great attention as potential immunosuppressive targets. Today, antibodies and other proteins are being developed to block these essential interactions, many of these reagents are now subject to clinical trials.

Once activated, the T cell is able to initiate, in particular through the cytokine, the final differentiation and proliferation of various other hematopoietic cells, such as B cells, cytotoxic T cells, NK cells, and macrophages. T cells may mediate effector functions resulting in tissue damage that may lead to graft rejection

ACTIVATION B  CELLS

Identification of antigen by B lymphocytes is somewhat simpler than in T cell because B cells are activated by direct interaction of native antigen with their surface antigen receptors (27).

The antigen receptor contains 4 chains that form a membrane-bound antibody version, these cells may eventually be secreted. This surface immunoglobulin (sIg) is bound to a protein complex that is analogously and structurally similar to the T cell CD3 complex.

Assimilation of antigen over sIg can result in degradation and presentation of T cells by MHC protein. Cross-linking of antigens and sIgs, in the presence of costimulatory signals, leads to proliferation of B cells, their differentiation in plasma cells that secrete a large amount of antibody.

As with T cells, costimulatory signals for the B cells may be in the form of cell-cell interactions, and may also be cytokines. Cell-cell interactions, where costimulatory signals are transmitted over CD19 / CD21 complexes and CD40s, are key.

The CD40 protein is a member of the TNF receptor superfamily and its cross-linking by the CD40 ligand present on T cells leads to an increase in proliferation and memory generation of B cells (27,28). Cytokines also play an important role in the proliferation and differentiation of B cells, with IL-2, IL-4, IL-5, IL-6 and IL-10 as most important.

HYPERACUTE REJECTION GRAFTS

Patients previously exposed to MHC antigens through transplants, blood transfusions or pregnancies often produce antibodies that are reactive with these MHC antigens. Such antibodies can undoubtedly be the cause of hyperacid rejection, when the organ falls down immediately after the transplant (29).

The tissue damage, in this case, is due to local complement fixation by antibody-related graft. Rejection is certainly accompanied by antibody and complement depletion and by the accumulation of polymorphonuclear leukocytes.

Today, it is possible to precipitate hyperacid rejection using pretransplantable skull test. This is a cross-match test that can detect antibodies specific to potential donor antigens. This test can detect not only harmful MHC specific antibodies, but also harmless autoantibodies (30).

In most cases today it is possible to distinguish between two types of antibodies, so it has become possible to transplant in an increasing number.

Interestingly, liver transplantation has been shown to be an exception to the transplantation rule besides a positive cross-correlation test.

In essence, liver transplantation is performed with very little insight into the immune system, it is performed successfully not only with a positive cross-correlation test, but without any probing of the donor and recipient match.

The reasons why liver transplants are so perfectly adaptive to the immune system have so far not been fully understood. It is assumed that the size and the enormous regenerative capacity of the liver are important. Thus, the immune response of liver grafts differs from that of other grafts and the understanding of this phenomenon can help us to create new immunosuppression strategies (31,32,33).

Although hyperacid rejection is almost always attributed to antibodies, in some situations, rapid rejection may occur even when the role of antibody is excluded. In these cases, in the case of rapid rejection, the cellular mechanism (34) plays a major role.

Today, there is an increased interest in xenotransplantation, where animal donors are used for human transplantation. Hyperactivity rejection is the main obstacle to xenotransplantation. The human organism often contains antibodies that react with cells of other species, which is the reason for the high incidence of hyperacid rejection. These antibodies are called "natural antibodies" because they are produced without prior exposure to xenotransplant. It is believed that these antibodies are produced against natural microflora of the intestine, and cross-react with cells of other species. Today, genetic modification of these grafts is being attempted, in a manner that prevents their rejection by recipients of another species!

 ACUTE DISCHARGE -REJECTION OF GRAPHTS

Acute rejection occurs in the first days or weeks after transplantation, before the introduction of strong immunosuppressive preparations, and undoubtedly results in a major loss of transplant. Early diagnosis and prevention of acute rejection has been analyzed for years. The analysis of the mechanism of acute rejection is the main focus of transplantation

INITIATION (INITIAL) OF ACUTE DISCHARGE-REJECTIONS

    TRANSPLANTS ORGANS

It has long been known that T lymphocytes play an essential role in the acute rejection of grafts. Experimentally, congenital atrial mice and other animals with excluded T cells did not reject either xeno or alografts. Of all T cells, the largest contribution to the rejection has the assistive T cell (Th cell). Assistive T cells are usually associated with CD4 + cells, for which experimental models generally found to play a major role in initiation of rejection, while CD8 + or not at all involved or only contributed to the rejection rate (35.36).

Pretty clear discoveries indicate that CD4 + cells are leading in the initiation of graft rejection but there is some confusion for some experiments. In these experiments, only a variety of mutant mutant mice ranging from only a few amino acids in their Class I molecules found only CD8 + cells as needed to establish graft rejection (37). These studies could be a reflection of the fact that it is possible in a limited number of cases to generate Class I controlled CD8 + Assistive Cells (38). Therefore, the position on the central role of the CD4 + cell in rejecting could modify the standpoint that T support cells, whether CD4 + or CD8 +, absolutely establish the initiation of graft rejection.

This is such a good, detailed and thoroughl explanation which included all aspects of immune responce and thank you for this scientific aspect.

Thank you Dr Marine in nice words and a very useful comment for me! It's great that you are following my projects and your suggestions are very useful to me in my future work!

Dear Prof. Jasenko. What can we do to improve our knowledge as to WHY human bodies still reject the transplants stemming from the foreign tissues, even though the immunosuppression was supposed to neutralize these unwanted/detrimental - organ rejecting developments ? 

I read recently that researchers at the University of Pittsburgh an Toronto have used genetic mapping approach and showed that molecule called SIRP alpha leads to immune system activation in the first step. When transplant SIRP alpha binds on CD47 on the monocytes , activation of immune system occurs. Blocking this interection give us opportunities to prevent organ rejection. So ,this is realy interesting topic for further research.

Answer dr Ridic:

You said everything in your comment, I have nothing to add!

Answer dr.Nejra:

This discovery is a great thing that can greatly improve and extend the survival period of the transplants and explain to us at the molecular level of the rejection reaction!

I am particularly pleased that two excellent US experts, Professor Fadi Lakis and Dr. David Rothstain, participated in this discovery, with whom I worked very successfully while I was on the Fulbright scholarship at the Yalu Schol of Medicine where they worked before Pittsburghu, what did they do I congratulate my heart!

Is it possible that the determination of immunosuppressive drugs can improve the success of organ transplant?

That, of course, is crucial for the development, progress and survival of the transplant is most closely related to the use of immunosuppressive therapy, which is crucial to stop the rejection rejection reactions!

With the following few of my answers and comments, I want to document the importance of immunosuppressive therapy in the success of organ transplantation!

I give a basic overview of the previous imo-suppressants, from their book, issued in 2012g. Under the title "Immunosuppressive Therapy and Its Use in Organ Transplantation", their activity and significance, which could further overcome the immunoblotic barrier through xenotransplantation by further training under these same principles. This book is entirely in electronic form on my CV on the web page of RG !

Introduction

Even 40 years ago, the first successful kidney transplant was performed between identical twins. The first attempts were unsuccessful or with a small amount of success because there was no adequate immunosuppressive therapy. The recipient organization sought to reject a foreign body by defensive immune response. Because of this, the experts worked on designing medications to develop effective immunosuppressive therapy. The first results are noticed in the practice of the 60s when the first immunosuppressive agents are being applied. Among the first are azathioprine (Imunran) and steroids. After some time, other medications such as mycophenolate mofetil that are slowly suppressing are occurring. From the age of 80, apart from ciclosporin, monoclonal antibodies block the function of T lymphocytes, resulting in immunosuppression. Monoclonal antibodies, which are routinely used with the CD3 glucoprotein, have a molecular weight of 20 kDa. OKT3 or mouse immunoglobulin, which is commercially used, has the ability to block the function of all T lymphocytes possessing this receptor. In the last 15 years many immunosuppressants have appeared that have a wide clinical application. Dr. Joseph Murray received the Nobel Prize in 1990 for successful work on kidney transplantation. The main strategy of clinical application of immunosuppressive is the reduction of the aloimic response to the transplanted organ. There are 4 major strategies in clinical practice: induction, prophylaxis of acute rejection, maintenance of immunosuppression and acute rejection therapy. Of course, the main goal of transplantation is to achieve absolute tolerance to the transplant, which will take time. For now, preventing transplant rejection is achieved by using powerful immunosuppressive medications at strictly prescribed doses to avoid toxic effects. Acute rejection occurs if no adequate suicide response is achieved. In cases of overactive immunosuppression, complications such as viral infections (Cytomegalo virus) or malignancy such as cancer of the skin, B cell lymphoma, Kaposi's sarcoma etc. may occur. For example, clinicians in the area of transplantation have limited possibilities to achieve effective results.

Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/3 [accessed Jun 30, 2017].

Immunosuppression, immunoinhibition, immunodeficiency, is the suppression and weakening of the normal immune response of the organism as a consequence of the action of different substances found in the external environment or created in the body. Each transplanted body represents a foreign body that the body is trying to discard. In order to avoid this, it is necessary to take anti-rejection drugs (immunosuppressive medicines). There are numerous medications as well as their combinations, however, all have a common one - they must be taken as long as the function of the transplanted organ takes place. Because immunosuppression of the immune system's function is weakened, there is an increased susceptibility of the organism to infectious diseases and cancer, so not so often immunosuppression can cause undesirable side effects.

Anti-suppression drugs (immunosuppressive drugs) have been the success of organ transplantation, which we are witnessing today. Unfortunately, they do not only act to prevent rejection of transplanted organs, but have many unwanted effects on the body. Especially important is reduced resistance to infections caused by immunosuppressive drugs. Treatment protocols are not unique to all transplantation centers. Transplant Centers decide on certain immunosuppression protocols according to the results of published clinical trials and their own experiences.

Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/4 [accessed Jun 30, 2017].

Anti-suppression drugs (immunosuppressive drugs) have been the success of organ transplantation, which we are witnessing today. Unfortunately, they do not only act to prevent rejection of transplanted organs, but have many unwanted effects on the body. Especially important is reduced resistance to infections caused by immunosuppressive drugs. Treatment protocols are not unique to all transplantation centers. Transplant Centers decide on certain immunosuppression protocols according to the results of published clinical trials and their own experiences.

Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/4 [accessed Jun 30, 2017].

Monoclonal antibodies which block adhesion molecule

Adhesion molecules are critical in the activation of immune cells and the filling within the allograft. They enhance antigen recognition by increasing the affinity of a T cell receptor and antigen-MHC complex. LFA-1 is a cell superficial protein comprising stimulatory signal for T cell activation. Intercellular adhesion molecules (ICAM-1 and ICAM-2) are specific ligands for LFA-1.

Anti-ICAM-1 monoclonal antibodies, inhibit CD4 + T cell activation in vitro and prolong allograft survival in animal models.

Anti-LFA-1 monoclonal antibody used for the problem of acute rejection with the same efficiency as anti-lymphocyte globulin, and also protects from falling behind in the functioning graft.

5.7. Monoclonal antibodies that block the T cell accessory molecules

Nepolimorfni accessory molecules are membrane proteins that serve as markers superficial cell, which are identical in all T cells. Important in the alloimmune response for stabilizing the interaction of cytotoxic T cells and target cells. They bind their specific ligands on the surface of target cells, two tepružaju signal for T cell activation. CD2 ligand for the LFA-3 molecule expressed antigen-presenting cells and endothelial cells. CD45 is superficial cellular glycoprotein expressed on all leukocytes and is a key regulator of T cell activity.

 LFA3TIP human protein is designed to block CD2-LFA-3 interaction. It has been shown to prolong survival of cardiac allografts in monkeys.

Anti-CD45 monoclonal antibody given during kidney transplantation damages companions leukocyte grafts.

BTI-322 is a rat monoclonal IgG2b antibody directed against CD2.

Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/5 [accessed Jun 30, 2017].

Induction of immunosuppression in transplanted kidney is one way to achieve the prevention of kidney transplant rejection in the recipient. The first three months are the most critical period after the transplantation and in this period immunosuppressive therapy must be strong enough to prevent rejection of the kidney. In that purpose, the biological agents such as polyclonal anti-lymphocyte antibodies, and murine monoclonal antibody preparations. Prophylactic immunosuppression antibodies can be prescribed as optional recipients of kidney termination and that for the purpose of reducing the number and level of acute reaction first 3-6 months after transplantation. There are two types of induction which are used to prevent early acute rejection, such as: therapy based on antibodies and aggressive early immunosuppression.

Therapy is based on antibodies is given in the early post-transplant period, and to avoid or reduce the dose of calcineurin inhibitors.

EARLY aggressive immunosuppression is used to maintain the drug at a higher dose to achieve the strongest immunosuppressive effect upon transplantation.

6.2. Prevention of acute rejection and immunosuppression maintenance

After the successful prevention of acute kidney allograft rejection is necessary to maintain the level of immunosuppression at a certain level. In this way reduces the incidence of acute rejection episode during the first six months after the translation. Home immunosuppressive maintenance therapy must be given prior to transplantation or at the time of transplantation. Immunosuppressants must be taken for life. Home immunosuppressive therapy and maintenance therapy, which was previously the most commonly used was a combination of cyclosporine, prednisone and azathioprine. For a long time, clinicians strategy was based on the use of two to three medicament, and thereby had to know which of them is dominant. Over time, regularly went to the reduction of the dose of a dominant immunosuppressive because of avoiding its toxicity. However, most patients showed a tendency toward lower doses of immunosuppressants, and it is considered that this is probably a result of the phenomenon of so-called. Accommodations allograft.

6.3. Therapy of acute rejection

Today there are three strategies against acute rejection. Many critics now use pulse corticosteroids as primary treatment in cases of mild to moderately intense acute rejection. When it comes to more aggressive form of acute rejection, which is typical for patients with arteritis in patients who do not respond to pulse steroids, in patients in whom corticosteroids are contraindicated, etc., Applied much more aggressive strategy of using preparations antimloimfocitnih antibodies. Terapcija of acute rejection can be short-lived success, and is determined by the improvement of the renal function and to an incidence of 90%.

Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/5 [accessed Jun 30, 2017].

 The strategy in cases of chronic allograft nephropathy

There is a specific approach to act in terms of the reserve. Efforts clinicians are reduced to minimize the influence nefrotosičnih agents such as calcineurin inhibitors, control of hypertension, renal perfusion opzimacija. Unless the cause of rejection is inadequate immune suppression, changes in immunosuppressive therapy are generally not effective in chronic rejection of the reserve. In addition to medications that are already in clinical practice, in the process of clinical evaluation are potential immunosuppressants that could essence involved in post-transplant treatment. Immunosuppressive agents therefore allows the protection of organ transplant rejection and for protection from side effects of recipient. Needle biopsies 11 days after transplant showing inflammatory damage of the small arteries. Sample hepatectomy obtained six weeks after transplantation showed lymphocytic infiltration involving all layers of medium sized arteries. Needle biopsy 4 months after transplantation shows perivenular nerkozu and lymphocyte infiltration.

 Biomarkers excessive immunosuppression

An important goal in transplantation is to adjust immunosuppression the individual needs of patients, avoiding the rejection and excessive immunosuppression. Monotoring immunosuppression is now mainly carried out on the basis of pharmacokinetic properties which do not necessarily foresee clinical outcome in an individual. The definition of a biomarker is actually characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to therapeutic intervention. Biomarkers are used for the prediction and monitoring of clinical response. It's hard to deifnisati adequate immunosuppression because they do not have enough knowledge about successful immunosuppression potrebnj for the prophylaxis or the treatment of rejection in an individual. Although there is no clear and sufficiently accepted definition of us-immunosuppression or excessive immunosuppression, for practical purposes, can be defined in terms of frequency and severity of infections and malignancies in patients during immunosuppressive treatment. Also, over-immunosuppression is shown as a leading cause of death after transplantation in Australia. Over-immunosuppression is a common and important problem after transplantation, and all approved immunosuppressant drugs contain a warning about the increased susceptibility to infection and the potential development of malignancy associated with the use of these drugs.

Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/5 [accessed Jun 30, 2017].

Infections malignancy

Infection and opportunistic infections occur mainly in the first year after transplantation, in response to strong initial immunosuppression. Malignancy occurs mainly after the first sir, an annual rate of 1% per year and it seems that the cumulative immunosuppression is an important factor. Each type of cancer has its own associated risk factors. Some post-transplant malignancies are associated with viruses, providing strong evidence for a close relationship between infection and malignancy.

Strategies for avoiding excessive immunosuppression and the role of biomarkers

The ideal solution to the problem of over-immunosuppression would be the development of protocols tolerance devoid of any immunosuppression, thus completely avoiding excessive immunosuppression. Given that such protocols tolerance currently unknown, closely related approach is the use of biomarkers in identifying tolerant patients. Such patients would no longer require immunosuppression, which would avoid further side effects of immunosuppressants. Sequential monitoring with biomarkers can help in the individualization of immunosuppressive regimens and such monitoring will be a complement to conventional monitoring of medicines. Ideally, these biomarkers to assist in the management of immunosuppressive therapy and would prevent the appearance of excessive immunosuppression without the need for further pharmacokinetic control, because any additional monitoring biomarkers increased burden of treatment. Currently there are a number of biomarkers (Table 1) that are directly (special mark) or indirectly (global markers) related to the pharmacodynamic effects of immunosuppressants.

Does the progress of immunosuppressive therapy can directly improve the possibility of the application of xenotransplantation?. Available from: https://www.researchgate.net/post/Does_the_progress_of_immunosuppressive_therapy_can_directly_improve_the_possibility_of_the_application_of_xenotransplantation/5 [accessed Jun 30, 2017].

 More about this you have in the author's book by Prof. Jasenko Karamehic, PhD and prof.dr.Sebija Izetbegovic and associates under the title: "Immunosuppressive therapy and its application in organ transplantation" issued in 2012 and is in electronic form on my CV at Reaserch Gate !

The understanding of transplant immunology has advanced from gross allograft rejection to cellular response and to current molecular level. More sensitive assays have been developed to characterize patient sensitization and to detect pre-existing donor-specific antibodies (DSA) in pre-transplant cross-match. After a transplant, pre-existing or de novo DSA are increasingly monitored to guide clinical management. Therefore, it is important for clinicians to understand the basic concepts and key components of transplant immunology as well as be familiarized with the modern immunological techniques used in kidney transplantation.

When a foreign organ, such as a kidney, is transplanted into a non-identical individual of the same species, the organ is called an allograft. The immune response from the recipient to the allograft is termed an (allo)-immune response.

Are artificial organs the future of organ transplantation since they could circumvent the immunological aspect issues of organ transplantations?

Excellent comment where everything sorted properly and I simply do not have the time to add!

 To think well ... to avoid the response of the recipient's immune system ... but it needs a lot ..., a lot of work to do ... to create an artificial-fetish organs ,  that simulates a completely real body!

How different  immunosuppressive  therapy improve the succsses of organ transplant?

What  kind of organ transplant will be in use more in the future; xenotransplantation or transpalnat of arteficiail organs?

Good questions for which I need a little more time to respond and I will be happy to answer you as soon as I get a little more time!

When we look to circumvent immunological barriers, in any case, it is a better vein organ than xenotransplantation due to differences in HLA systems of different species, and this is a major problem in today's transplantation immunology, which is not easy to solve!

About this I would like to give you more comprehensive comments from which one can see how complicated the problem is ...!

INTRODUCTION

Xenotransplantation is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues, or organs are called xenografts or xenotarnsplants. Human xenotransplantation offers potential treatment for the terminal stage of organ insufficiency, which today represents a major global problem. The dimensions of this problem, as well as advances in immunotherapy, have spawned a great interest in potentially using animals instead of people as organ donors. Researchers in this field have directed their efforts to suppress the immune barrier that prevents long-term survival of xenograft. Xenotransplantation is also associated with many medical, legal and ethical issues. The use of xenotransplantation for clinical purposes would involve a multidisciplinary approach in order to more fully respond to various issues related to the use of xenographs for human purposes. In this regard, security, ethics and regulatory aspects of xenotransplantation are now working to achieve the best possible conditions in which the ratio Between risk and benefit was as favorable as possible.

DEFINITION

Xenotransplantation implies any procedure involving transplantation, implantation, infusion into a human recipient, any living cell or fire from an inhuman animal source, or any human body fluid, cell, tissue, organ that had an ex vivio contact with living nonhuman cells of the tissues or organs. (US Food and Drug Administration / FDA, 1999, FDA, 2001)

Xenotransplant products must be alive. For example, human skin cells that grow outside the body, on the surface of non-human cells, and are used to reconstitute the skin in humans, can also be considered a xenotransplant product. This category of procedures is included in the definition of xenotransplants because scientists consider the potential transmission of infection with these procedures has similarities with transmission of infection in the transplantation of living animal cells, tissue or gum to human donor.

CLINICAL EXPERIENCE IN XENOTRANSPLANTATION

The founders of organ transplantation are Alexis Carell and Charles Guthrie. The development of vascular anastomosis in the early 1900s allowed investigators to develop a technique of organ transplantation. Carell and Gutrie performed the leg replanting in a dog, and developed a known patches of graft techniques for the expansion of narrowed blood vessels. They also worked on heteroropic experimental transplantation. It is important to emphasize that initial xeno and allotransplants functioned only for a short period of time. In these pioneering beginnings, the most common reasons for rejection were related to technical problems or with essential incompatibility. Bearing this in mind, the use of vascular anastomosis in organ exchange had to wait for the development of effective immunosuppression therapy that occurred at least 50 years later.

When immunosuppressive agents became available in the early 1960s, human organs were still rarely available, which forced researchers to turn to the possibility of xenotransplantation. In the Early 60s, Reemstm's scientist managed to transplant a 12-kidney kidney from a chimpanzee monkey to human recipients. The clinical development of these transplants was characterized by episodes of decreased renal function, which is analogous to acute cell rejection. The loss of transplantation was associated with infection in 2 recipients and acute cell rejection at 6 recipients. Some of the transplants worked for months, the longest of which was 9. In that period, knowledge of transplantation immunology and immunosuppressive therapy was minimal. By using modern immune suppressive therapy and antibiotics, these transplants could enjoy a long lasting survival period.

In the near past, liver baboon monkeys were transplanted into 2 human subjects with failure, ie, rejection. Although the recipients of the liver from the baboon monkey eventually died, it appeared that the transplanted organs showed histological signs of rejection.

While the results described above could be considered promising, there are serious limitations in the use of non-human mammals of the highest order as organ donors, even if ethical problems can be solved. Many mammals of the highest order are too small, and large mammals do not have enough to satisfy the current need for the necessary organs. An important detail for xenotransplantation was observed in the 1990s, when a pork retrovirus was detected. The problem of the risk of transmission of infection among species has resulted in many clinical studies in the field of xenotransplantation.

. IMMUNOLOGICAL BARRIERS IN KSENOTRANSPLANTATION

To date, there are not fully adequate answers to the questions of xenotransplantation, due to numerous obstacles that arise from the response to the recipient's immune system. This response, which is generally higher than in allotransplants, ultimately results in the discouraging of xenograft. There are several types of xenograft rejection, which implies:

• Hyperacute rejection

• Acute vascular rejection

• Cell rejection

• Chronic rejection

CURRENT STATUS AND GUIDELINES

     XENOTRANSPLANTATION

Xenotransolation and Xenotransplantation products are known to be under the FDA regulatory authority, and the FDA has formed a BRAMAC / Biologic Response Modifiers Advisory Committie as the current mechanism for open discussions on scientific, medical, ethical, and societal health issues raised concerning xenotransplantation.

The FDA has developed a transitional transposition action plan to create an approach to regulate xenotransplantation. This approach implies regulation of public health and safety issues in the case of xenotransplantation. Additionally, this approach gives guidelines to sponsors, manifactures and researchers on the safety of clinical research and monitoring.

Occasionally, the FDA issues brochures that help researchers and sponsors interested in research in the field of xenotransplantation. These documents contain guidelines for the safety of xenotransplantation products and the course of clinical trials, with particular reference to recommendations on the qualifications of procurement and screening of animal sources, testing of animal products, and post-transplant monitoring and survival of animal transplant recipients. The FDA informs and invites the public to comment and discuss these documents, and organize meetings and work groups focusing on xenotransplantation issues. Such gatherings help to change information and involve the public in the issues of xenotransplantation.

FUTURE OF XENOTRANSPLANTATION

It might seem strange that a manual that addresses practical issues relating to the practice of medical disciplines of transplantation and immunology should take into account such a hypothetical subject such as xenotransplantation. In all likelihood, the lack of human organ donors is such a serious problem that interest in xenotransplantation has increased significantly. With the advancement in the development of methods that focus on the processes: 1.) "Consumption" of human antibodies and to 2.) Inhibition of the complementary system, the problem of hyperacute rejection does not seem to be an insurmountable obstacle. It can be said that acute vascular rejection, which is currently unclear, could now seem to be the main humoral barrier to xenotransplantation. If acute vascular rejection can be prevented by approaches that are useful in treating hyperacute rejection, then clinical xenotransplantation might become possible. If accommodation would be found, which would allow resistance to acute vascular rejection, then clinical xenotransplantation could be further developed.

In the future, clinical xenotransplantation can achieve the desired goal of achieving prolonged survival of graft, using and learning from allotransplantation lessons.

LITERATURE

1. Hickman R, Saunders SJ, Goodwin NE, Terblance J. Perfusion of the isolated pig liver with human blood. J Surg Res, 1971; 11: 519-527.

2. Cooley DA, Gallman GL, Bloodwell RD, Nora JJ, Leachman RD, Human heart transplantation: experience with twelve cases. Am J Cardiol, 1968; 22: 804-810.

3. Abouna GM, Serrou B, Boehmig HG, Amemiya H, Martineau G. Long-term hepatic support by intermittent multi-species liver perfusions. Lancet, 1970; 2: 391-396.

4. Nalesnik MA, Fung JJ, Strazl TE, Demetris AJ. Pathology studies in two baboon to human liver xenograft cases. Transpl. Proc, 1994; (In press).

5. Auchincloss H Jr. Xenogeneic transplantation. Transplantation, 1988; 46: 1-20.

6. Reemtsma K. Xenotransplantation: a personal history. In: Xenograft 25, Hardy MA, (ed.) New York: Elsevier Science Publishers, 1989; 7-16.

7. Collins BH, Chari RS, Magee JC, Harland RC, Lindman BJ, Logan JS, et al. The immunopathology of porcine livers perfused with the blood of humans with fulminant hepatic failure. Transplantation, 1994; 58: 1162-1171.

8. Welsh KI, Taube DH, Thick M, Palmer A, Stevens N, Binns RM. Human antibodies to pig determinants and their association with hyperacute rejection of xenografts. In: Xenotransplantation. Transplantation of organs and tissues between species, Cooper DKC, Kemp E, Reemtsma K, White DJG, (eds.). New York: Springer-Verlag, 1991; 501-510.

9. Czaplicki J, Blonska B, Relgia Z. The lack of hyperacute xenogeneic heart transplant rejection in a human. J Heart Lung Transplant, 1992; 11: 393-398.

10. Jooste SV, Clovin RB, Winn HJ. The vascular bed is the primary target in the destruction of skin by antiserum. J Exp Med, 1981; 154: 1332-1341.

11. Starzl TE, Fung J, Tzakis A, et al. Baboon-to-human transplantation of the liver. Lancet. Jan 9, 1993; 341 (8837): 65-71.

12. Rood PP, Cooper DK. Islet xenotransplantation: Are we really ready for clinical trials ?. Am J Transplant. Jun 2006; 6 (6): 1269-74.

13. Chatterjee DS. A controlled comparative study of the use of porcine xenograft in the treatment of partial thickness of skin loss in an occupational health center. Curr Med Res Opin. 1978; 5 (9): 726-33.

14. Fink JS, Schumacher JM, Ellias SL, et al. Porcine xenografts in Parkinson's disease and Huntington's disease patients: preliminary results. Cell Transplant. Mar-Apr 2000; 9 (2): 273-8.

What is your opinion about how the improvement in clinical immunological laboratory tests will affect the success of organ transplantation?

In which phase of organ transplantation, is more important to apply clinical laboratory tests, before organ transplantation in the preparation of the patient or after organ transplantation?

Of course the development of better immunological diagnostics in the tissue typing phase and finding a matching one close to the complementary HLA donor is the key to the success of organ transplantation!

It is important in all stages of organ transplantation, I speak from my experience, I think that it is most important in tissue typing when there is a cross between the potential recipients and donors in determining amongst other cytotoxic antibodies ... and other immunological parameters and this is the key to success or eventual failure of transplantation Organs! About this I will give you a much more comprehensive and detailed answer soon!

LABORATORY ANALYSIS FOR THE EVIDENCE OF BIOMARKER IMMUNOLOGY TRANSPLANTATION REACTION

To evaluate the threat of transplantation and post-transplantation, an important issue is in planning and selecting the appropriate treatment and treatment of the recipient. For several years, it has been working intensively on the development of laboratory tests in predicting and evaluating the risk of rejection, applicable in clinical practice. The goal is to disable the rejection and to recognize a recipient who can lower the level of immunosuppressive therapy or maybe completely discontinue the use of the drug. The drugs are administered according to the manufacturer's recommendation. The amount of drug measured in the blood is not directly correlated with the amount taken. The differences are the result of the individual pharmacokinetics of the drug, as well as the measurement method. In addition, the level of the drug measured by the immunoassay is not correlated with the immunosuppressive effect. Immunological reactivity in the function of post-transplant time depends on the type of organ and interaction with other medicines used. It is obvious that such a test would contribute to a more complete understanding of the mechanisms underlying the rejection, but also the tolerance of the graft.

The issue of an ideal prognostic test returns us back to the past when HLA typing was introduced, the HLA coincidence, serum cross-reaction, and mixed-cell lymphocyte culture tests (MLC). For many years, MLC and mediated limphysis-CML (CML) engl.cell mediated lympholysis have been used as a provider of specific in vitro rejection models. Various tests are being investigated today for the purpose of predicting and confirming rejection or tolerance. In relation to these tests, they can be broken down in relation to the part of the rejection rejection for which they are most informative, namely: the recognition of alloantigens, the rejection reactions and the regulation of the reaction. In relation to the alloimmune reaction, we will specifically focus on recognition and rejection tests.

Identifying acceptable mismatch

The harmful immunological response is mainly directed towards allogeneic HLA molecules, but minor tissue-related tissue antigens may be the goal of an alloimmune reaction. The prognostic value of the cross reaction test proved unavoidable in excluding prospective recipients with a positive reaction to the digestive antigens. Although the detection of anti-HLA antibodies is the primary purpose of the test, it also has a prognostic value in recognizing the resulting allanticillin associated with chronic rejection.

Taking into account the dominance of the main system of tissue support of the GSH, the choice of matching potential recipients can prevent the severity of the alloimmune reaction to foreign tissue. By developing modern techniques that are quick and thorough, such as HLA typing, the provider-recipient has improved the compliance with a better clinical outcome. Recent research has warned that the immunogenicity of HLA discrepancy can be different. Testing can identify HLA discrepancies that we say are> acceptable

Antigen specific tests in the monitoring of alloimmune reactions

Although we can structurally determine the permissible differences between the donor and the potential recipient of the organ, the functional immunogenicity of these differences remains. A mixed culture of lymphocytes-MLC (MLC, lymphocyte culture) and CML-mediated lymphocytes were used in in vitro assays to monitor aloeactivity versus the discrepancy between HLA class I and II. In reality, these are not quantitative tests and only have a limited possibility of predicting the events in vivo.

By introducing a limiting dilution assay-LDA (LDA, according to the English limiting dilution assay), the possibility of determining the frequency of precursors of alloreactive helper lymphocytes T (fThp) and cytotoxic lymphocytes T (fCTLp).

This test has shown that there are individual differences between different individuals according to the same HLA antigens in the frequency of the precursor cells, but also each person has a different frequency of the precursor cells, according to different HLA discrepancies. These findings gained their clinical significance when significantly lower values of fCTLp were obtained in combination with acceptable antigens compared to values for immunogenic HLA differences. Recent research points to the possibility of adjusting immunosuppressive therapy, using the results of measuring the activity of alloreactive cytotoxic lymphocytes T (fCTLp).

Overdose with immunosuppressive drugs remains a problem after organ transplantation. In patients with the expected average functioning of the graft between 15 and 25 years, long-term and non-harmonized immunosuppression is a serious complication, with side effects. The intensity and frequency of side effects are directly related to immunosuppression. In several studies, it has just been shown that a small number of precursors provide specific cytotoxic lymphocytes T (fCTLp) predicted to change the therapy free from sudden rejection. Measurement of alloreactive helper lymphocytes T before transplantation can serve as a parameter of the strength of post-transplant reactions and adaptation to therapy.

One-time measurements of the frequency of alloreactive Thp in the recipient with a poorly developed graft rejection reaction resulted in low values of (fThp) IL-2 cells.

Measurements of different executive functions can be determined at different times. In addition to proliferation, the secretion of cytokines allows determination of auxiliary lymphocytes T (fThp) precursors and the executive activity can be demonstrated by determining the precursor of cytotoxic lymphocytes T (fCTLp).

The presence of a panel of reactive alloantibodies (PRA) in the patient's serum suggests an increased risk of postmenoplantic damage to the prescription, mediated antibody. According to this sample, a reactive T cell (PRT) panel was set up, which tests the reactivity of the recipient to the allogeneic cells of the INF-g stimulator by an ELISPOT test, predicting the power of executable aloreactive cells with memory.

LABORATORY DETERMINATION OF ALOANITIEL AND ALOANTIGEN

All patients on the waiting list for transplantation are subject to a quarterly check of the degree of sensitization to HLA antigens. The patient's serum is tested against a combination of non-native lymphocytes (panel lymphocytes) that are phenotypically different in HLA antigens. The number or size of the panel meets the requirement that all HLA antigens are represented twice in different HLA phenotypic combinations. The presence of anti-HLA antibodies is determined by a standard cytotoxicity test, a complement-dependent test. When reading the reaction, we use an estimate of the number of dead cells that are in the basin of the terasaki tile. This traditional method is increasingly being supplemented with the ELISA test. This method denotes the so-called. A solid phase of PRA determination, wherein the HLA packs ticks or microparticles for an enzyme immunoassay that can be identified by flow cytometry. This, a new method is particularly suitable when donor cell providers are not available. In a recipient with a high% PRA, there is a possibility of desensitization by the use of plasmapheresis and intravenous human immunoglobulin (IVIG). The efficacy and effectiveness of IVIG can be checked by an in vitro assay. The method is useful for clinical practice, contributing to the decision on the application of therapy with a very expensive preparation.

Cross reaction

A cross reaction is the most important test that is performed immediately before transplantation. Today, several different methods of performing the test are available, including flow cytometry, a generally applicable complement-dependent complement of micro-immune-cytotoxicity. In the cross-reaction test, there is the same principle of reading the strength of the reaction and the assessment of a positive and negative test. In addition, it is necessary to list the so-called. A virtual cross reaction (the basis is in the specificity of the HLA antibody of the recipient and the antigen of the provider), which has been described in more recent times. Preference is given to non-sensitized recipients, while low sensitivity to PRA-positive patients

Determination of cytokine concentration

The concentration of cytokine is determined in serum samples. All samples must be stored without preservatives. Immunological tests related to the sensitization and cross reaction of the subjects are also carried out on the samples. Cytokinin is determined by commercial enumeration immunodeficiency kits - ELISA. For positive and negative control, commercial and own serum samples are used. This in vitro assay yields the quantitative values of the test cytokine

Non-invasive molecular monitoring of graft function

Several labs are used in laboratories that prove to be more important in monitoring the prescription function. We are increasingly encountering tests using molecular diagnostic techniques. Very often, the urine is used as a sample. Determining the level of mRNA for lP-10 and CXCR3 during the rejection process refers to the circulation of cells involved in the process. Chronic rejection, which is the main cause of graft loss, mediated by changes in the blood capillary walls, real-track PCR, determine TGF-β mRNA. It is known that TGF-β and CTGF (connective tissue growth factor) affect the proliferative and inflammatory response in the prescription. In addition to determining tissue damage markers, CD4 + CD25 + FOXP3 cells provide the ability to protect the digestive tract from the alloimmune reaction. Determining the level of FOXP3 mRNA in urine cells gives an insight into the reversal of the acute rejection episode and the protective regulatory response .

What is you oppinion which period in development of clinical immunology is crucial in organ transplantation?

You have long been involved in clinical immunology and you know its development and importance in organ transplantation. What is your opinion, which scientist has left the deepest influence in clinical immunology?

Since you are professor of pharmacology, and you are familiar with this field, could you please provide me with information what is your experience which immunosuppressive drug is best for overcoming immunological barrier in organ transplant?

Thank you very much for asking and very interesting questions that require me to answer them individually, and I will use my books and papers in which I have described in detail the issues that you have actualized in your questions or comments!

I think that in the 1950s, the beginning of the development of transplantation immunology with pioneer and Nobel Prize winner Medaver is, in my opinion, the most important for overcoming immune biological barriers and after the great development of this area and the discovery of new immunosuppressive drugs ... it has led to the great development of this important field in medicine!

Thank you for your interesting question, my answer would be:

should be very near the development of immunosuppression, lot of effort and research in front of HLA tissue and improve diagnosis better match the donor and recipient, the molecular and genetic level, reduce the potential for immune-biological barrier better coincidence loss and reduced linearly quantified number of cytotoxic antibodies, that are a big risk for graft rejection transplant, especially in front of tipizacion and the early stage of transplantation ...., also improve precision and expand the range of clinical and immunological tests.

Improve also ,  early screening markers for early detection of early stages of rejection, to affirm and improve donor network in the sense of the affirmative influence to increase the number of donors, in particular the cadaver transplantation   and thus broaden the basis and greater number of potential donors and their better chances to find more compatible donors thereby proportionately reducing the risk of immunological rejection of reason, life , extend the shelf life graft id event was lower doses of immunosuppressive drugs or reduce their side effects ....!

Once again thank you for the successful cooperation ...!

What is the role of clinical immunology in organ transplants?. Available from: https://www.researchgate.net/post/What_is_the_role_of_clinical_immunology_in_organ_transplants/1 [accessed Jul 13, 2017].

Historical Perspectives on Relevance Immunology

       transplant

It is generally accepted that the early work of scientists in the field of behavioral Medawar allo-transplant skin gene in laboratory rabbits, first published in the period 1944th-1946th, marked the formal beginning of modern transplantation period. The historical background of the time domain bears special relevance to our topic. Most of incentives to early research ventures in the field of transplant originated in the war-torn Great Britain in the 1940s, during the intensive efforts of the British and surgeons volunteers from other countries to treat and rehabilitate the pilots of Royal Air Force who were injured and mutilated during the legendary fighting for UK. One of the members of the volunteer surgical team, the late John Marquis Converse, worked closely with Sir. Harold Gillies employee in center for plastic surgery Park Prewett Hospital in Basingstoke, Hampshire.

During one of the many Converse's surgical operation, in the process of transplanting skin of a RAF pilot, Sir Harold is brought into the operating room, a tall, skinny, young zoologist from Oxford University and said, "Doctor Medawar is interested in the problem homograft. This declaration marked the beginning of a long friendship between Converse and Medawar, after talks in which the Medawar expressed special interest in the behavior of skin homograft and to process their rejection. During the discussion, it has been hypothesized that in case if the epidermis, which in itself has no blood vessels, could be separated from the vascular dermis, epidermis then it could survive as a free graft. Converse gave a piece of skin Medawar, who returned to the lab and divide the epidermis from the dermis using raw-unsophisticated preparation Trypsin, which is in itself contained an enzyme elastase. The resulting leaf epidermis was placed on the patient granulation surface wounds, but he was gone by tomorrow.

What is the role of clinical immunology in organ transplants?. Available from: https://www.researchgate.net/post/What_is_the_role_of_clinical_immunology_in_organ_transplants/1 [accessed Jul 13, 2017].

The continuation of the answer by Dr. Marini Delic-Sarac to the first question, I will repeat the answers I have already given in this project

This was Medawarovo first exposure to transpantiranju skin in humans, and this has led to its collaborative efforts with respected British plastic surgeon, Dr. Tom Gibson, with whom he Medawar published a classic study on human subjects. This experience has also marked the beginning of Medawarovog systematic experimental study of skin grafts rabbit, which has produced a basic foundation for the role of immunology in rejecting allografts. Converse enduring fascination with the field of transplantation is very intensified its work in Basingstoke-in. After his return to civilian life in 1948, he established one of the first America transplantation research laboratory at Bellevue Hospital in New York, and there was soon attracted a talented team of associates. (5)

Converse has early realized the need for frequent exchange of ideas between the then small society of doctors and biologists all over the world who have an interest in transplantation. Converse attended the conference, researcher in 1951, at a conference in Arden home, which was attended by the now legendary names as: TS Hauschka, D. M. Hume, N.Kaliss, C.C. Little, W. Longmire, R.E. Maumenee, PB Medawar and among others GD Snell. This meeting was initiated Conversa to seek ways and means to establish regular channels of exchange between the members of this new scientific discipline.

Converse has assured members of the Academy of Sciences of New York to sponsor a series "of International Conference on transplant" in order to provide the focal point for meetings in the various disciplines that were beginning to enter the field of transplantation. The first International Conference in the series, called "The attitude of Immunology at Homo tissue transplantation", held in New York in 1954. This name was not accidental; one of Conversovih most significant achievements during the year was the direct involvement of professional immunologists in transplantation.

What is the role of clinical immunology in organ transplants?. Available from: https://www.researchgate.net/post/What_is_the_role_of_clinical_immunology_in_organ_transplants/1 [accessed Jul 13, 2017].

The continuation of the answer by Dr. Marini Delic-Sarac to the first question, I will repeat the answers I have already given in this project

Converse was convinced that the immunological approach was crucial to allow progress in our understanding allograftske reactivity.

Upon arrival at Bellevue Hospital in 1948, Converse has spent years trying to incorporate leading immunologists New York City, especially with the Rockefeller Institute of New York University, who had connections with the transplant. Unfortunately, during this period classical immunologists are looking to transplant with a touch of suspicion. Something in the spirit of a short memoir called "peripatetic school (Peripatetics) immune Surgeon," which was presented at the Fifth International Congress of the Association of transplantation, 1974:

"I remember well how we pray immunologists to attend to the early conferences. One immunologist visionary, Rueben L. Kahn, he finally agreed to come on the first Konferenciju- and scientific field called immunology is now a senior member of the club. The irony in all, in fact, that indicates that the transplant research then quickly sparked a renaissance-boom in the field of immunology orthodox ... "

The huge success of the conference on the "Attitudes Immunology with Homotransplantacijom Tissues" has begun to attract a growing number of prominent immunologist world-class on 6-th row transplant conference, sponsored by the New York-ery Academy of Sciences in the period 1956th-1966th Converse was chaired and organized by each of these meetings. He also collected the funds necessary to finance the costs of the conference and travel costs of experts. Issued "The conclusions of this conference," constitute a unique historical document, in which every modern principle of transplantation biology and medicine was presented and discussed, in a joint forum of general scientists and medical professionals (clinicians).

Exceptional is the fact that almost every central concept or hypothesis which supports our current efforts in the field of transplantation was first formulated in one of the above conferences. One early additional product of the First Conference of the New York Academy of Sciences, was the first successful kidney transplant, 10 months later (December 23, 1954),

What is the role of clinical immunology in organ transplants?. Available from: https://www.researchgate.net/post/What_is_the_role_of_clinical_immunology_in_organ_transplants/1 [accessed Jul 13, 2017].