Transplant Rejection: Causes, Types and Prevention

transplanting Rejection Causes, Types and PreventionThrough this project I get hold of researched shifts of variety meat, cells and meanders, Transplant rejection, the kind Immune System and the position of antibodies. Transplatation is the process where healthy cells, waver or reed harmoniums argon moved from one site to a nonher. There ar disparate types of transplants and many problems that keister come on with transplantation. The largest threat to a successful organ transplant is the Human Immune System, because it rejects the transplant.The role of the tender resistor dust is to protect the proboscis from bad, infecting agents. It destroys the transplant recognizing it as contrasted and a potential treat to the frame. This is kn accept as Transplant Rejection.There argon many different types of Transplant Rejection, each with there own diagnosis methods and symptoms. There are different ways of prevention and treatment, including interweave typing to det ermine the most appropriate donor- pass receiver match and using Immuno curbant drugs that suppress the tolerant skeletal frameation of rules of the recipient.There are two kinds of immunity in a human. The corpses first line of defence is the Innate electric metro and the special(prenominal) resolution to the invaders is the Adaptive Immunity. Many white blood cells multifariousness the main components of the resistive system and they bring out and destroy incursive agents.There are also different types of resistive responses including the Humoral immune response. Antibodies, Y-shaped proteins, form part of the Humoral response. The structure of all antibodies are very similar, except for a small unique neighborhood at the ends of the two arms of the Y used for recognising agents. Antibodies can destroy the foreign material or help destroy them by tagging it for attack by other parts of the immune system.Antibodies are very crucial in transplant rejection, because t hey form part of the mechanism that rejects the organ or tissue and are one of the most important cells of the Human Immunity System. They help lead to Transplant Rejection and the destruction of the transplanted organ or tissue.INDEX (Jump to)Introduction possible actionTransplantsTypes of TransplantsProblems With organ transplantTransplant RejectionTypes of Transplant RejectionDiagnosis and SymptomsPrevention and TreatmentPotential Further StudiesThe Human Immune System and AntibodiesTypes of Immune ResponsesConclusionBibliography ReferencingINTRODUCTIONThe role of the Human Immunity System is to protect the consistency from harmful, infecting agents. This protection is very important to keep our bodies healthy and functioning at the best it can, but this protection is also the largest problem in organ and tissue transplants.Transplantation has replaced many people damaged organs with healthy organs and is used to cure many tissue and cell diseases. The Human Immunity System is the largest threat to successful organ and tissue transplants, but why does the Human Immunity reject the transplanted organ or tissue? And is it possible that transplant rejection can be prevented?The eubstance is constantly under attack from harmful substances that can cause damage and destruction to the human body, but we are protected. The human immunity system is bodys natural defence mechanism. What causes an immune response? And how does the immune system respond to foreign materials?Antibodies are an important part in the human immunity system. They can recognize, neutralize and destroy harmful materials, but what exact role does an antibody play in human immunity? Where and why are antibodies produced?Through this project I ordain explore transplants, transplant rejection, human immunity and the role of antibodies and finally prove or run afoul my hypothesis.HYPOTHESISAntibodies do not play a role in the rejection of a transplanted organ or tissue.TransplantsTransplatat ion is the action of healthy cells, tissue or organs that are transplanted (grafted) from one site to another. A transplanted organ can replace a recipients damaged, malfunctioning or absent organ and grafting of cells and tissue can also cure many diseases.A kidney (most common), heart, lungs, pancreas, liver, skin, cornea, blood, blood vessels, bone marrow, stem cells, cord blood, intestine, stomach, testis, thymus, bones, tendons, heart valves and veins, hand, Islets of Langerhans and ovaries can now be transplanted. The transplanted organ or tissue is commonly dwelln as a graft.While the lack of organs for transplantation remains an obstacle, the biggest challenge for transplantation is the immune system. It destroys a transplanted graft recognizing it as foreign and a potential treat to the body. 279111213141516171819202122Types of TransplantsAutografts Grafts of tissue from one area of the body to another part e.g. Skin transplants, vein extractions, etc. Autografts are not f oreign tissue and therefrom there is no immune reply.Allografts Grafts between members of the identical species. Most organ transplants are allografts. Because of genetic differences between the organ and the recipient, the recipients immune system ordain identify the organ as foreign and attempts to destroy it, causing transplant rejection.Isografts Forms part of allografts and are grafts between genetically identical individuals. Isografts do not trigger an immune response.Xenografts/ Xenotransplantation Grafts between members of different species. E.g. the use of organs from other animals, exchangeable chimpanzees, baboon and pigs. In Xenografts there is a large adventure of rejection and diseases carried in the tissue. 279192022Problems with TransplantationGraft/transplant rejection The immune system, recognizing the transplanted graft as foreign, will cause a rejection of the graft.Graft-versus-host disease (GVHD) T-cells, in the graft from the donor, identify the tissues of the recipient as a foreign antigen and mounts an immune attack against them. This is prevented by removing all T-cells in the graft before transplantation.In rare cases the donated organ whitethorn be infected and transmit an agent to the recipient. E.g. TB, rabies, syphilis, hepatitis B, HIV and many other diseases. To prevent this, potential donors are tested for these infections before the transplantation. 21219Transplant RejectionTransplant rejection is also know as Graft Rejection and organ or tissue rejection.Transplant Rejection occurs when a transplanted organ or tissue is not accepted by the body of the recipient, because the immune system of the recipient attacks and tries to destroy the transplanted organ or tissue. The body identifies the graft as foreign material and therefore triggers a rejection.This is expected because the Human Immunity Systems purpose is to protect the body by identifying and destroying foreign material that are potentially harmful. These harmf ul substances have proteins called antigens on their step forwards, when the immune system identifies these antigens as foreign, it will start to attack them.The degree and type of response varies according to the type of transplant and the organ or tissue being transplanted. Certain sites in the body are immune privileged, which means they are protected from attack, because immune cells and antibodies do not reach them. The anterior chamber of the eye, the testes and the brain are all immune privileged.Using the patients own tissue for autografts or tissue from an identical twin, isografts, when available prevents transplant rejection as the recipient sees the transplant as self, not as foreign and therefore does not mount an attack. Using a relative (sibling) as a donor is also recommended, because they may have inherited some of the same histocompatibility antigens and therefore the immune response may not be as strong. 23478111223Types of Transplant RejectionHyperacute Rejectio nHyperacute Rejection is a rare humoral complement-mediated response in recipients with pre- costing antibodies to the donor. This reaction occurs immediately subsequently the transplantation. No treatment is available for it and the graft must be removed quickly to prevent a severe systemic rabble-rousing response or death.Acute RejectionAcute rejection usually begins one week after the transplant, but it can occur months to years after transplantation. The new organ will be incapable of working at full efficiency. A single episode of acute rejection is not dangerous, if it recognized and treated it rarely leads to organ failure.Acute rejection occurs to some degree in all transplants and is caused by mismatched HLA. The Immune system will recognize the graft as foreign and will mount an attack against it. Acute rejection is a form of Cell-mediated response.Humeroral RejectionHumeroral Rejection is mediated by antibody and complement Immunity. It can occur immediately or during the first week after the transplantation. The antibodies are preformed antibodies or anti-donor antibodies that have girded after transplant.Chronic RejectionChronic Rejection is the rejection against a graft due to chronic inflammatory and immune response. This rejection occurs over quantify (sometimes years after the transplant) and may occur from repeated episodes of acute rejection or for other causes not understood.Chronic Rejection is rare and is both antibody cell-mediated immune responses. Chronic rejection is irreversible and there is no successful treatment. Eventually the donor organ is lost, leading to re-transplant or death. 37823Diagnosis and SymptomsDiagnosis of transplant rejection relies on clinical data, including signs and symptoms, lab test and a tissue biopsy to confirm that the graft has been rejected. The biopsy is interpreted by a pathologist who notes changes in the tissue that suggest rejection. E.g. presence of T-cells and other cell types that may be helpful in diagnosing the type of rejection and any evidence of structural injury or injury to blood vessels in the transplanted tissue.The symptoms of transplant rejection diverge depending on the organ or tissue transplanted, but general symptoms include the organ not functioning properly, general discomfort, uneasiness or ill feeling, unhinge or swelling in the location of organ (rare) and fever (rare). 123Prevention TreatmentTissue TypingTransplant rejection can be reduced done serotyping (tissue typing or crossmatching) before the transplantation to identify the antigens it contains and to determine the most appropriate donor-recipient match. ABO blood typing or HLA (Tissue antigen) typing is performed to ensure that the organ or tissue is as similar as possible to the tissues of the recipient.The antigens responsible for rejection of tissues are called histocompatibility antigens. These antigens are encoded by genes on chromosome 6, called the Major Histocompatibility Comp lex (MHC). The MHC is called the Human Leukocyte Antigen (HLA) system in humans. HLA are present on all cells of the body. Each individual has a unique combination of HLA and matching as many histocompatibility antigens will pick at the size and speed of rejection.MHC molecules present antigens to the T-cells of the immune system. When a foreign material enters a body cell, the MHC molecules inside the body cell bind to the antigen and transport it to the body cells surface. The antigen can now be recognized by a T-cell.Immunosuppressant DrugsImmunosuppressant drugs can treat and prevent transplant rejection. The drugs suppress the immune system of the recipient and are usually necessary for all transplants to prevent the graft from being rejected. The drugs should be used for the rest of the transplant recipients life.Most immunosuppressive drugs have the disad vantage of being non-specific and they result in suppression of the entire immune responses and therefore placing the rec ipient at a higher risk of infections. It is needed to develop more specific immunosuppressive drugs that will suppress only the responses that attack the graft, without dangerous side effects.Drugs like azathioprine (Imuran), methotrexate, cyclophosphamide, prednisone, belatacept, corticosteroids, cyclosporine A, tacrolimus, prednisolone, mycophennolate mofetil, antithymocyte globulin (ATG) and rapamycin are routinely used in different combinations for a safe level of immunosuppression.Side effects of immunosuppression drugs include infections, as the immune system is vital to protect us from infectious agents (bacteria, viruses, fungi, etc). usually the infections can be controlled by the appropriate antibiotic, antiviral drug, etc. The chance of Cancer is also increased with the use of immunosuppression drugs. 12567812161923Potential Further StudiesDemi-Lee Brennan, an Australian whose body changed blood type and adopted the immune system of her donor after a liver transplant. H er body no longer rejects the transplanted liver. Her case is unique and scientists are interested in finding out how this occurred. Duplication of this would be a potential solution to transplant rejection. nigh grafts survive despite the presence of anti-donor antibodies. This acquired resistance to antibody-mediated damage is known as Accommodation and is poorly understood. 68The Human Immune System and AntibodiesThe immune system recognizes as foreign and attacks anything different from your normal body tissues. Even substances that are only slightly different, for example a transplanted organ or tissue, are considered foreign invaders.The immune system uses histocompatibility antigens to recognize material as self or foreign. Antigens occur on the surface of every cell and the immune system will attack anything that does not display the antigen of that individual. The immune system cannot tell if the foreign material is harmful or not, just that it is different. The transplante d organ or tissue is different and therefore the immune system will under institute to destroy it.There are two kinds of immunity in a human, Innate Immunity and Adaptive Immunity. The bodys first line of defence against invaders is the Innate Immunity. It is provided by barriers like tears, mucus, skin, saliva and the rapid inflammation of tissue. If an invader gets past the Innate Immunity, the immune system will make a customized defence, the Adaptive Immunity. It is a specific response depending on the specific invader and it has a memory, which allows it to respond better to the specific invader if it attacks again. The Adaptive Immunity does not attack normal body components, only substances it recognizes as non-self.White blood cells (leukocytes) are the main component of the immune system. Macrophages, a type of white blood cells, surround and eat invading materials. Macrophages can also attach to themselves to invading agents and transport them to another part of the immun e system to be destroyed. Lymphocytes are specialized white blood cells that identify and destroy invading antigens. Each lymphocyte has a unique antigen sensory receptor on its surface that can bind to a matching antigen on the surface of the foreign invader. They constantly travel throughout the body looking for invaders. All lymphocytes begin as stem cells in bone marrow, but they mature in two different places.Several lymphocytes mature in the bone marrow and they are called B-lymphocytes (B-cells). B-cells form Plasma cells that make antibodies. Each B-cell has a unique receptor on its membrane, called B-cell receptor (BCR) that is designed to fit a specific antigen. When the BCR binds to an antigen molecule, the B-cell surrounds it and breaks it up. The result is the histcompatibilty molecules and then the body B-cell can identify the antigen.Other lymphocytes called T-lymphocytes (T-cells) mature in the thymus. Some T-cells called cytotoic or Killer T-cells directly destroy cells that are displaying a certain antigen on their surface. Other T-cells, Helper T-cells, regulate the immune system by arbitrary the strength of immune responses. 135678101123Types of Immune ResponsesHumoral Immune ResponseThe Humoral response attack invaders that act outside of cells, like bacteria and poisons.When an invader antigen enters the body, Macrophages take the antigen and attach it to MHC molecules. The MHC molecules display the antigen to the T-helper cells and they attach to the presented antigen. This stimulates the T-helper cells to divide and produce interleukins. The Interleukins activate a B-cell that has bound the antigen. The activated B-cells then divide and give up antibodies.Antibodies, also called immunoglobulins (lg), are Y-shaped proteins and they are found in blood and other bodily fluids of vertebrates. Antibodies are produced by a kind of white blood cell, called a plasma cell.Surface immunoglobulin are attached to the membrane of the effector B-c ells, while antibodies are the secreted into the bloodstream and body cavities. The membrane-bound form of an antibodies is forms part of the BCR on B-cells.The general structure of all antibodies are very similar, except for a small region at the ends of the two arms of the Y used for binding antigens. This allows many different antigen binding sites to exist between the antibodies, allowing the immune system to recognize a wide diversity of antigens.The base of the Y determines how the antibody will destroy an antigen or foreign material. Antibodies into are sort into 5 classes/isotypes lgM, lgG, lgA, lgD and lgE. They perform different roles and form part of the immune response against foreign objects.The secreted antibodies bind can the antigen and destroy it. Antibodies may also stop the harmful effects of an antigen by attaching to it and neutralizing it. Antibodies also help destroy antigens by tagging it for attack by other parts of the immune system.Cell-mediated Immune Re sponseThe Cell-mediated Response attacks invaders, like viruses, that reproduce inside cells. It also destroys cells that cause the growth of improper structures, like cancers.After an invader antigen enters the human body, Macrophages attach the antigen to MHC molecules. The MHC molecules present the antigen to the T-helper cells and they bind the antigen, which motivates the T-helper cells to divide and secrete interleukins. The Interleukins activate killer T-cells. Killer T-cells directly destroy the cell/s that are infected with or that are producing a certain antigen. 3781011CONCLUSIONMy Hypothesis that antibodies do not play a role in the rejection of a transplanted organ or tissue is incorrect. Antibodies are very important in transplant rejection, because they form part of the mechanism that rejects the organ or tissue and they are one of the main components of the Human Immunity System.When the healthy organ or tissue is transplanted into the body of the recipient, it does not have the same tissue antigens of the recipients body. Each human has unique tissue antigens, therefore a perfect match is seldom found.Antibodies form part of humoral rejection response to the transplanted organ or tissue. They are the main element in recognizing a foreign agent, because they have unique antigen binding sites. Antibodies especially play a role in Hyperacute, Humeroral and Chronic Transplant Rejection, as they are all humoral-mediated rejections.Anti-Donor antibodies are secreted by plasma cells after the T-helper cells have unruffled the transplants antigen and identified it as foreign and non-self. Pre-existing antibodies circulate through the bodily fluids of the human body looking for foreign material to recognize. Some antibodies also form part of the membrane receptor of the B-cells used to identify and recognize antigens of the transplanted organ or tissue.After the antibodies have bond to the foreign antigen of the transplanted organ or tissue, therefore recognizing it, it will decide how to destroy the organ or tissue or if it will tag it for attack from other parts of the immune system. Leading to Transplant Rejection and the destruction of the transplanted organ or tissue.BIBLIOGRAPHY REFERENCINGWebsiteshttp//www.nlm.nih.gov/medlineplus/ency/article/000815.htm, Transplant Rejection, Medline Plus, 23 February 2010, David A. 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