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Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient. This is explained by the concept that the immune system of the recipient attacks the transplanted organ or tissue. This is expected to happen, because the immune system's purpose is to distinguish foreign material within the body and attempt to destroy it, just as it attempts to destroy infecting organisms such as bacteria and viruses. Image File history File links Question_book-3. ... Transplant redirects here. ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Phyla/Divisions Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Omnibacteria Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular, bacterium) are a major group of living organisms. ... This article is about biological infectious particles. ...

Types of rejection

Hyperacute rejection

Hyperacute rejection is a complement-mediated response in recipients with pre-existing antibodies to the donor (for example, ABO blood type antibodies). Hyperacute rejection occurs within minutes and the transplant must be immediately removed to prevent a severe systemic inflammatory response. Rapid agglutination of the blood occurs. This is a particular risk in kidney transplants, and so a prospective cytotoxic crossmatch is performed prior to kidney transplantation to ensure that antibodies to the donor are not present. For other organs, hyperacute rejection is prevented by transplanting only ABO-compatible grafts. Hyperacute rejection is the likely outcome of xenotransplanted organs. A complement protein attacking an invader. ... Each antibody binds to a specific antigen; an interaction similar to a lock and key. ... This article is about human blood types (or blood groups). ... In medicine, systemic inflammatory response syndrome (SIRS) is an inflammatory state of the whole body (the system) without a proven source of infection. ... The kidneys are the organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. ... (xeno- from the Greek meaning foreign) is the transplantation of living cells, tissues or organs from one species to another such as from pigs to humans (see Medical grafting). ...

Acute rejection

Main article: Histocompatibility

Acute rejection usually begins one week after transplantation (as opposed to hyperacute rejection, which is immediate). The risk of acute rejection is highest in the first three months after transplantation. However, acute rejection can also occur months to years after transplantation. A single episode of acute rejecction is not a cause for concern if recognised and treated promptly, and rarely leads to organ failure. But recurrent episodes are associated with chronic rejection (see below). This article or section does not adequately cite its references or sources. ...

Acute rejection occurs to some degree in all transplants (except those between identical twins). It is caused by mismatched HLA antigens, which are present on all cells of the body. There are a large number of different alleles of each HLA antigen, so a perfect match between all HLA angigens in the donor tissue and the recipient's body is extremely rare. HLA region of Chromosome 6 The human leukocyte antigen system (HLA) is the name of the human major histocompatibility complex (MHC). ... An allele is any one of a number of alternative forms of the same gene occupying a given locus (position) on a chromosome. ...

Tissues such as the kidney or the liver which are highly vascularized (rich in blood vessels), are often the earliest victims of acute rejection. In fact, episodes of acute rejection occur in around 60-75% of first kidney transplants, and 50 to 60% of liver transplants. Damage to the endothelial lining of blood vessels is an early predictor of irreversible acute transplant rejection. The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ...

The reason acute rejection usually begins one week after transplantation is that T-cells are involved in the rejection mechanism. These T-cells must differentiate before rejection begins. The T-cells cause cells in the transplanted tissue to lyse, or produce cytokines that cause necrosis of the transplanted tissue. Lysis (Greek lusis from luein = to separate) is the reduction of symptoms of a disease the dissolving of cells osmotic lysis chemical lysis viral lysis a dialogue of Plato about friendship (philia) This is a disambiguation page — a navigational aid which lists other pages that might otherwise share the same...

The first successful organ transplant, performed in 1954 by Dr. Joseph Murray, was successful because the donor and recipient were identical twins, and therefore no T-cell-mediated responses could be generated against the transplanted organ. Joseph E. Murray (born 1 April 1919), American surgeon, performed the first successful human kidney transplant from an adult to his identical twin. ...

The diagnosis of acute rejection relies on clinical data, including patient signs and symptoms, laboratory testing and ultimately a tissue biopsy. The biopsy is intrepretated by a pathologist who notes changes in the tissue that suggest rejection. Generally the pathologist looks for three main histological features. First, the presence of T-cells infiltrating the transplanted tissue; these may be accompanied by a heterogeneous collection of other cell types including eosinophils, plasma cells and neutrophils. (The proportions of these cell types may be helpful in diagnosing the exact type of rejection.) Secondly, evidence of structural injury to the transplanted tissue; the characteristics of this injury will depend on the type of tissue being transplanted. Lastly, injury to the blood vessels in the transplanted tissue. Brain biopsy A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... A thin section of lung tissue stained with hematoxylin and eosin. ... T cells are a subset of lymphocytes that play a large role in the immune response. ... Eosinophil granulocyte Eosinophil granulocytes, commonly referred to as eosinophils (or less commonly as acidophils), are white blood cells that are responsible for combating infection by parasites in the body. ... Plasma cells are B lymphocytes that secrete immunoglobulins (antibodies). ... Neutrophil granulocytes (commonly referred to as neutrophils) are a class of white blood cells and are part of the immune system. ...

Chronic rejection

The term "chronic rejection" was initially a term used to describe a long-term loss of function in transplanted organs, associated with fibrosis of the internal blood vessels of the transplanted tissue. But this pathology is now termed chronic allograft vasculopathy. The term chronic rejection is reserved for cases of transplant rejection where the rejection is due to a chronic immune response against the transplanted tissue. It can be caused by a member of the Minor Histocompatibility Complex such as the H-Y gene of the male Y chromosome. This usually leads to need for a new organ transplant after a decade or so. Fibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue. ...

Rejection mechanisms

Rejection is an adaptive immune response and is mediated through both T cell mediated and humoral immune (antibodies) mechanisms. The number of mismatched alleles determines the speed and magnitude of the rejection response. Different grafts usually have a proclivity to a certain mechanism of rejection. The adaptive immune system is composed of highly specialized, systemic cells and processes that eliminate pathogenic challenges. ...

Treatment of rejection

Chronic transplant rejection is irreversible and cannot be treated effectively. The only definitive treatment is re-transplantation, if necessary. This would typically be ten years after a transplant, and this may entail returning to a transplant queue.

Acute transplant rejection can be treated using chemotherapeutic drugs designed to suppress the immune system (see list below). Acute rejection is normally treated initially with a short course of high-dose corticosteroids, which is usually sufficient to treat successfully. If this is not enough, the course can be repeated or a triple therapy regimen can be used, consisting of a corticosteroid plus a calcineurin inhibitor and an anti-proliferative agent. Antibodies against specific components of the immune system can be added to this regimen, especially for high-risk patients. mTOR inhibitors can be used in selected patients, where calcineurin inhibitors or steroids are contraindicated. Acute rejection refractory to these treatments may require blood transfusions to remove antibodies against the transplant. In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... Immunosuppressive drugs or immunosuppressants are drugs that are used in immunosuppressive therapy to inhibit or prevent activity of the immune system. ... The title given to this article is incorrect due to technical limitations. ...

If a bone marrow transplant can be performed, the transplant recipient's immune system can be replaced with the donor's immune system, thus enabling the recipient's body to accept the new organ without risk of rejection. This requires that the bone marrow, which produces the immune cells, be from the same person as the organ donation (or an identical twin or a clone). Bone marrow is not attacked by the body's immune system, and is the only known type of transplant that has this quality. However, there is a risk of graft versus host disease (GVHD) in which the immune cells arising from the bone marrow transplant recognise the host tissues as foreign and attack and destroy them accordingly. Bone marrow transplantation or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). ... Fraternal twin boys in the tub The term twin most notably refers to two individuals (or one of two individuals) who have shared the same uterus (womb) and usually, but not necessarily, born on the same day. ... For the cloning of human beings, see human cloning. ... Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...

Immunosuppressive drugs used to treat transplant rejection

• Calcineurin inhibitors
  • Cyclosporin
  • Tacrolimus
• mTOR inhibitors
  • Sirolimus
  • Everolimus
• Anti-proliferatives
  • Azathioprine
  • Mycophenolic acid
• Corticosteroids
  • Prednisolone
  • Hydrocortisone
• Antibodies
  • Monoclonal anti-IL-2Rα receptor antibodies
    • Basiliximab
    • Daclizumab
  • Polyclonal anti-T-cell antibodies
    • Anti-thymocyte globulin (ATG)
    • Anti-lymphocyte globulin (ALG)

The monoclonal anti-T cell antibody OKT3 was formerly used in the prevention of rejection, and is occasionally used in treatment of severe acute rejection, but has fallen out of common use due to the severe cytokine release syndrome and late post-transplant lymphoproliferative disorder, which are both commonly associated with use of OKT3; in the United Kingdom it is available on a named-patient use basis only. Calcineurin (CN) is a protein phosphatase also known as protein phosphatase 2B (PP2B). ... ... Tacrolimus (also FK-506 or Fujimycin) is an immunosuppressive drug whose main use is after allogenic organ transplant to reduce the activity of the patients immune system and so the risk of organ rejection. ... The title given to this article is incorrect due to technical limitations. ... Sirolimus is a relatively new immunosuppressant drug used to prevent rejection in organ transplantation, and is especially useful in kidney transplants. ... Everolimus is a new mTOR inhibitor drug used as an immunosuppressant to prevent rejection of organ transplants. ... Azathioprine is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation, autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease such as Crohns disease. ... Mycophenolic acid (INN) (IPA: ) or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... Prednisolone is the active metabolite of prednisone. ... Hydrocortisone is a synthetic corticosteroid drug which may be given by injection or by topical application. ... Basiliximab (Simulect) is a chimeric mouse-human monoclonal antibody to the IL-2Rα receptor of T cells. ... Daclizumab (Zenapax) is a murine-human chimaerised monoclonal antibody to the IL-2Rα receptor of T cells. ... Anti-thymocyte globulin (ATG) is an infusion of rabbit-derived antibodies against human T cells which is used in the prevention and treatment of acute rejection in organ transplantation. ... Anti-lymphocyte globulin (ALG) is an infusion of horse-derived antibodies against human T cells which is used in the treatment of acute rejection in organ transplantation, especially in kidney transplants. ... Cytokine release syndrome is an common immediate complication occurring with the use of anti-T cell antibody infusions such as ATG and OKT3. ... Post-transplant lymphoproliferative disorder (PTLD) is the name given to a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant. ...

Other treatments

An FDA-approved immune function test from Cylex has shown effectiveness in minimizing the risk of infection and rejection in post-transplant patients^[1] by enabling doctors to tailor immunosuppressant drug regimens. By keeping a patient's immune function within a certain window, doctors could adjust drug levels to prevent organ rejection while avoiding infection. Such information could help physicians reduce the use of immunosuppressive drugs, lowering drug therapy expenses while reducing the morbidity associated with biopsies, improve the daily life of transplant patients, and could prolong the life of the transplanted organ. The United States Food and Drug Administration is the government agency responsible for regulating food, dietary supplements, drugs, cosmetics, medical devices, biologics and blood products in the United States. ... Cylex, Inc is a biotechnology company developing and manufacturing products that use the immune system for predicting and managing human health. ...

Please be aware this an expensive method that is useful but does not paint the full picture. If it were that simple, most centres would adopt it and less costs to the consumer. However rejection is far more complex than just measuring the immune function. The cytotoxic T-lymphocyte precursor frequency, which is a once off test is far more accurate in reading a person's immune status.

Demi-Lee Brennan

Demi-Lee Brennan is an Australian citizen who after a liver transplant has changed blood type and adopted the immune system of her donor. The upshot of this is that her body no longer attempts to reject the transplanted liver ^[2] and she therefore does not need immunosuppresant medication.^[3] Transplant redirects here. ... This article is about human blood types (or blood groups). ... A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Immunosuppression is the medical suppression of the immune system. ...

Her case is described as unique in that there were no other recorded instances of this ever happening in the history of human organ transplanting. Scientists are now interested in finding out how this happened in hopes of duplicating the process since this may be a solution to the problem of transplant rejection.^[2]

References

This article deals with The Daily Telegraph in Britain, see The Daily Telegraph (Australia) for the Australian publication The Daily Telegraph is a British broadsheet newspaper founded in 1855. ... ABC News is a national news service produced by the News and Current Affairs division of the Australian Broadcasting Corporation. ...

External links

• The Immune Tolerance Network