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Using the patients own tissue for autografts or tissue from an identical twin, isografts, when availiable 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 recommened, because they may have inherited some of the same histocompatibility antigens and therefore the immune response may not be as strong.
Hyperacute Rejection is a rare humoral & complement-mediated response in recipients with pre-eisting antibodies to the donor. This reaction occurs immediately after the transplantation. No treatment is availiable for it and the graft must be removed quickly to prevent a severe systemic inflammatory response or death.
Acute 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 effeiciency. A single episode of acute rejection is not dangerous, if it recognized and treated tt 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 Rejection is mediated by antibody and complement Immunity. It can occur immediately after the transplant or during the first week. The antibodies are preformed antibodies or anti-donor antibodies that develop after transplantation.
The symptoms of transplant rejection vary depending on the organ or tissue transplanted, but general symtoms include the organ not functioning properly, general discomfort, uneasiness or ill feeling, pain or swelling in the location of organ (rare) and fever (rare).
Prevention & Treatment
Tranplant rejection can be reduced through 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 are encoded by genes on chromosome 6, called the major histocompatibility complex (MHC). In humans, the MHC is called the Human Leukocyte Antigen (HLA) system. HLA are present on all cells of the body. Each individual has a unique combination of HLA and matching as many histocompatibility antigens will minimize the size and speed of rejection.
The function of the MHC molecules is to present antigens to T cells of the immune system. When a foreign material enters a body cell, the MHC molecules inside the body cell attach themselves to the antigen and transport it to the body cell's surface. The antigen can now be recognised by a T-cell.
Fig5: Tissue Typing
Immunosuppressant drugs can treat and prevent transplant rejection. The drugs suppress the immune system of the recipient and is usually necessary for all transplants to prevent the graft from being rejected. The drugs should be used for the rest of the transplant recipient's life.
Most immunosuppressive drugs have the disadvantage of being non-specific and they result in suppression of immune responses to all foreign bodies, thus placing the recipient at increased 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.
Fig6: Immunosuppressant Drugs
Source: http://www.bartsandthelondon.nhs.uk/ilibrary/ar43_drugs.jpgSide effects of immunosuppression drugs include infections, as the immune system is vital to protect us from infectious agents (bacteria, viruses, fungi). 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.
Potential Futher Studies
Demi-Lee Brennan, an Australian whose body changed blood type and adopted the immune system of her donor after a liver transplant. Her 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.
Some grafts are known to survive despite the presence of anti-donor antibodies. This acquired resistance to antibody-mediated damage is known as Accommodation and is poorly understood.
The Human Immune System and Antibodies
The immune system recognizes as foreign and attacks anything different from your normal body tissues. Even substances that are only a little bit different, like a transplanted organ or tissue, are considered as invaders. When an organ or tissue is transplanted, it is recognized as foreign and your immune system attacks it.
Fig7: Human Immunity
Source: http://zombieresearch.files.wordpress.com/2009/08/zzz-immune.jpgThe immune system uses histocompatibility antigens to recognise material as "self" or foreign. Antigens are found 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 transplanted organ or tissue is different and therefore the immune system will try to destroy it.
There are two kinds of immunity in a human. Innate Immunity and Adaptive Immunity. Innate immunity is the body's first line of defence against invaders. 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 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 deliver them to other parts of the immune system to be destroyed. Lymphocytes are specialized white blood cells that identify and destroy invading antigens and each lymphocyte has a unique antigen 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.
Fig8: Human Blood
Source: http://www.textbookofbacteriology.net/imgcid.jpgSome lymphocytes mature in the bone marrow and they are called B-lymphocytes (B-cells). B-cells form Plasma cells that make antibodies, which circulate through the body, sticking to foreign antigens and destroying them. Each B-cell has a unique receptor on its membrane, called B-cell receptor (BCR) that is designed to fit one specific antigen. When the BCR binds to an antigen molecule, the B-cell engulfs it and breaks it up. The molecules that result are the histompatibilty 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 controlling the strength of immune responses.
Types of Immune Responses
Humoral Immune Response
The 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 secrete interleukins. The Interleukins activate any B-cell that has bound the antigen.The activated B-cells then divide and secrete antibodies.
Antibodies are Y-shaped proteins called immunoglobulins (lg) 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.
Fig9: Antibodies at work.
Surface immunoglobulin are attached to the membrane of the effector B-cells, 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 recogize a wide diversity of antigens.
The base of the Y decides how the antibody will destroy an antigen or foreign material. Antibodies into are classified 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 be able to 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.
Fg10: Antibody Structure
Cell-mediated Immune Response
The 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 body, Macrophages take up the antigen and attach it to MHC molecules. The MHC molecules present the antigen to T-helper cells and they bind the antigen, which stimulates 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.