Transplant rejection occurs when the immune system of the recipient of a transplant attacks the transplanted organ or tissue. This is because a normal healthy human immune system can distinguish foreign tissues and attempts to destroy them, just as it attempts to destroy infective organisms such as bacteria and viruses. The immune system protects the host from infection by pathogenic organisms. ... An organ transplant is the transplantation of an organ (or part of one) from one body to another, for the purpose of replacing the recipients damaged or failing organ with a working one from the donor. ... 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. ... Groups I: dsDNA viruses II: ssDNA viruses III: dsRNA viruses IV: (+)ssRNA viruses V: (-)ssRNA viruses VI: ssRNA-RT viruses VII: dsDNA-RT viruses A virus (Latin, poison) is a microscopic particle that can infect the cells of a biological organism. ...

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 coagulation 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. ... Schematic of antibody binding to an antigen An antibody or immunoglobulin is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Blood type is determined, in part, by the ABO blood group antigens present on red blood cells A total of 29 human blood group systems are recognized by the International Society of Blood Transfusion (ISBT). ... In medicine, systemic inflammatory response syndrome (SIRS) is an inflammatory state of the whole body (the system). It is characterized by: fast heart rate (tachycardia, heart rate >90 beats per minute) low blood pressure (systolic <90 mmHg or MAP <65 mmHg) low or high body temperature (<36 or >38°C... Human kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... Bold textJohan heeft een dikke LUL believe me i know grtz gertjan!!! Hoi A4T, Leuk he ANW. Ja geweldig!!!! GERBEN STINKT Im gOd. ...

Acute rejection

Acute rejection is generally acknowledged to be mediated by T cell responses to proteins from the donor organ which differ from those found in the recipient. Unlike antibody-mediated hyperacute rejection, development of T cell responses first occurs several days after a transplant if the patient is not taking immunosuppressant drugs. Since the development of powerful immunosuppressive drugs such as cyclosporin, tacrolimus and rapamycin, the incidence of acute rejection has been greatly decreased, however, organ transplant recipients can develop acute rejection episodes months to years after transplantation. Acute rejection episodes can destroy the transplant if it is not recognised and treated appropriately. Episodes occur in around 60-75% of first kidney transplants, and 50 to 60% of liver transplants. A single episode 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 of grafts. The bulk of the immune system response is to the Major Histocompatibility Complex (MHC) proteins. MHC proteins are involved in the presentation of foreign antigens to T cells, and receptors on the surface of the T cell (TCR) are uniquely suited to recognition of proteins of this type. MHC are highly variable between individuals, and therefore the T cells from the donor recognize the foreign MHC with a very high frequency leading to powerful immune responses that cause rejection of transplanted tissue. Identical twins and cloned tissue are MHC matched, and are therefore not subject to T cell mediated rejection. The first sucessful organ transplant was performed between identical twins by Dr. Joseph Murray at the Peter Bent Brigham Hospital in Boston. This transplant was successful because no T cell mediated reponses were generated to the transplanted organ. Dr. Murray later received a Nobel prize for his work. MHC I (1hsa) vs MHC II (1dlh) (more details. ... 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. ... Cloning is the process of creating an identical copy of an original organism or thing. ...

Chronic rejection

Chronic rejection was a term used to describe all long term loss of function in organ transplants associated with fibrosis of the internal blood vessels of the transplant, but this is now termed chronic allograft vasculopathy and the term chronic rejection is reserved for those cases where the process is shown to be due to a chronic alloreactive immune response. 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 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 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. ...

Prevention of rejection

Rejection is prevented with a combination of drugs including:

• Calcineurin inhibitors
  • Ciclosporin
  • 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)

Generally a triple therapy regimen of a calcineurin inhibitor, an anti-proliferative, and a corticosteroid is used, although local protocols vary. Antibody inductions can be added to this, especially for high-risk patients and in the United States. mTOR inhibitors can be used to provide calcineurin-inhibitor or steroid-free regimes in selected patients. Calcineurin (CN) is a protein phosphatase also known as protein phosphatase 2B (PP2B). ... Ciclosporin (INN), cyclosporine or cyclosporin (former BAN), is an immunosuppressant drug. ... Tacrolimus (also FK-506 or Fujimycin) is a 23-membered macrolide lactone discovered in 1984 from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. ... 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 immunosuppresant drug used to prevent rejection in organ transplantation. ... In physiology, corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. ... {stub} ... Hydrocortisone is a synthetic corticosteroid drug which may be given by injection or by topical application. ... Basiliximab (Simulect) is a murine monoclonal antibody to the IL-2R&#945; receptor of T cells. ... Daclizumab (Zenapax) is a murine-human chimaerised monoclonal antibody to the IL-2R&#945; 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. ...

A bone marrow transplant allows the chimeric body's immune system to adapt and accept a new organ. 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 (BMT) 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). ... Look up chimera, Chimaera in Wiktionary, the free dictionary. ... 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. ... Cloning is the process of creating an identical copy of an original organism or thing. ... Graft-versus-host disease is a common complication of allogeneic bone marrow transplantation. ...

Treatment of rejection

Acute rejection is normally treated initially with a short course of high-dose methylprednisolone, which is usually sufficient to treat successfully. If this is not enough, the course can be repeated or ATG can be given. Acute rejection refractory to these treatments may require plasma exchanges to remove antibodies to the transplant. Methylprednisolone (molecular weight 374. ...

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. 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. ...

Acute rejection usually begins after the first week of transplantation, and most likely occurs to some degree in all transplants (except between identical twins). It is caused by mismatched HLA antigens that are present on all cells. HLA antigens are polymorphic therefore the chance of a perfect match is extremely rare. The reason that acute rejection occurs a week after transplantation is because the T-cells involved in rejection must differentiate and the antibodies in response to the allograft must be produced before rejection is initiated. These T-cells cause the graft cells to lyse or produce cytokines that recruit other inflammatory cells, eventually causing necrosis of allograft tissue. Endothelial cells in vascularized grafts such as kidneys are some of the earliest victims of acute rejection. Damage to the endothelial lining is an early predictor of irreversible acute graft failure. The risk of acute rejection is highest in the first 3 months after transplantation, and is lowered by immunosuppressive agents in maintenance therapy. The onset of acute rejection is combatted by episodic treatment.

Chronic 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.

External links

• The Immune Tolerance Network