Reaction of rejection of a transplant
- Symptoms of Reaction of rejection of a transplant
- Reasons of Reaction of rejection of a transplant
- Treatment of Reaction of rejection of a transplant
Prevalence of operations on transplantation of fabrics (bodies) considerably increased in clinical practice for the last two decades.
The factors limiting transplantation of fabrics are immunological reactions against the replaced cells and existence of the appropriate donor organs. The autotrasplantation — transplantation of own tissues of the owner from one part of an organism in another (skin, bones, veins), and also exchange of fabrics between genetically identical (monozygotic) twins does not cause immunological reactions of rejection (isotransplant) as fabric is perceived as "". At change of white grafts (for example, corneas) reaction of immunological rejection does not appear as lack of blood circulation in a transplant prevents contact of immune cells with antigens, and development of an immune response requires contact of antigen with cells of immune system. Transplantation of fabric between genetically diverse people causes the immunological answer which can lead to rejection. Expressiveness of reaction of rejection increases in process of growth of genetic distinctions between the donor and the recipient. Now almost all bodies change from people.
Symptoms of Reaction of rejection of a transplant:
Graft rejections has several forms: from the rapid reaction proceeding within several minutes after transplantation before slow reactions, the shown disturbance of functions of the replaced fabrics in several years after transplantation. The mechanisms involved in these various types of rejection are also various.
The acute rejection
The acute rejection — the fulminant reaction proceeding within several minutes after transplantation and characterized by a heavy necrotic vasculitis with ischemic injury of a transplanted organ. Accumulation of cell-bound immune complexes and complement activation in a wall of the involved vessels can be defined by immunological methods.
The acute rejection is caused by presence at serum of the recipient of high levels of the preexisting antibodies against antigens on the replaced cells. Reaction of antibodies with antigens causes immunocomplex (like Artyus's phenomenon) damage to transplant vessels. After the beginning of use of the technology of direct definition of compatibility of fabrics the acute rejection became a rarity.
Acute rejection is observed quite often and can proceed from several days to one months after transplantation. It is acute because even if signs of rejection appear in several months after transplantation and quickly progresses from the moment of its beginning. Acute rejection is characterized by a necrosis of cells and disturbance of functions of body (for example, an acute necrosis of a myocardium and heart failure at heart transplantation). At acute rejection both humoral, and cellular mechanisms participate. Cell-bound immune complexes are deposited in small vessels of a transplant and cause the acute vasculitis leading to ischemic changes. Cellular immune rejection is characterized by a necrosis of parenchymatous cells and a lymphocytic infiltation of fabrics. At renal transplantation acute rejection is shown in the form of an acute renal failure as a result of a necrosis of renal tubules with lymphocytic infiltration of intersticial fabric. To the prevention and treatment of acute rejection apply immunosuppressive drugs, for example, corticosteroids (Prednisolonum) and cyclosporines, or anti-lymphocytic serum which destroys the patient's T-cells.
Chronic rejection is observed in the greatest number of the replaced fabrics and causes the progressing deterioration in function of body within months or years. Patients often have episodes of acute rejection suspended by immunosuppressive therapy. At chronic rejection cellular immunity (the IV type of hypersensitivity) is activated that leads to progressive destruction of parenchymatous cells. In the struck fabric fibrosis with lymphocytic infiltration develops. In certain cases presence of a chronic vasculitis indicates parallel influence of antibodies. At treatment of chronic rejection try to reach balance between damage of a transplant and expressiveness of toxic influence of immunosuppressive drugs which are usually used for prevention of rejection.
Reasons of Reaction of rejection of a transplant:
At graft rejection a play a role and humoral, and cellular mechanisms. Though graft rejection is considered sometimes as manifestation of a phenomenon of hypersensitivity because there is a damage of cells, it is actually normal immune response on alien antigens.
Humoral mechanisms are mediated by antibodies which can be present at serum of the recipient before transplantation or develop after change of alien fabric. Preoperative definition of already present antibodies against the replaced cells is carried out by direct definition of compatibility of fabrics which is carried out by in vitro statement of reaction between cells of the donor (blood lymphocytes) and serum of the recipient. Humoral factors damage the replaced fabric by reactions which are equivalent to hypersensitivity reactions II and III types. Interaction of antibodies with antigen on a surface of the replaced cells leads to a necrosis of cells, and accumulation of cell-bound immune complexes in blood vessels activates a complement that leads to development of an acute necrotizing vasculitis or chronic fibrosis of an intima with vasoconstriction. Immunoglobulins and a complement in such drugs can be found by immunological methods.
Cellular mechanisms of rejection cause T lymphocytes which become sensibilized to the replaced antigens. These lymphocytes cause damage of cells by direct cytotoxicity and by secretion of lymphokines. Damage by T-cells is characterized by a necrosis of parenchymatous cells, a lymphocytic infiltation and fibrosis. Cellular mechanisms in the course of rejection are more important, than humoral.
Treatment of Reaction of rejection of a transplant:
Apply two essentially various approaches to suppression of graft rejection: creation of specific tolerance of the recipient to a transplant and use of the means which are not specifically suppressing an immune response of an organism on alien Ag.
Creation of tolerance at transplantation.
This approach has undoubted advantage as does not interfere with normal development of immune responses on others, first of all infectious, Ag. At tolerance development the immune conflict does not develop and there is permanent engraftment of a transplant. Now similar researches were not beyond an experiment, and achievements of clinical transplantology first of all are connected with improvement of methods of nonspecific immunodepressive therapy.
Basis of effect of immunodepressants — suppression of metabolism of immunocompetent cells. Immunodepressants often have cytostatic effect and on cells of other fabrics. The modern arsenal of transplantology contains chemical and biological immunodepressants. In certain cases, mainly at bone marrow transplantation, their use is supplemented with the ionizing radiation. Perhaps general irradiation in low doses, local radiation of a spleen and a thymus gland, radiation of a transplant, and also extracorporal radiation of blood and a lymph of the recipient.
• Steroid hormones (Prednisolonum, Methylprednisolonum, dexamethasone) suppress proliferation of lymphocytes in lymph nodes and a spleen and reduce quantity of lymphocytes in blood. Antimetabolites include analogs purine (for example, an imuran or Azathioprinum) and the pirimidinovy bases (5-ftoruratsit, 5-bromoksipiridin, etc.), antagonists of folic acid (Amethopterinum, a methotrexate) and alkylating agents.
• Analogs of the purine and pirimidinovy bases. Proliferation of immunocompetent cells at an antigen challenge is connected with synthesis in them nucleic acids. Assimilation by cells of analogs of initial products of synthesis of nucleic acids (the purine and pirimidinovy bases) leads to blockade of this process and oppression of proliferation of immunocompetent cells.
• Antagonists of folic acid block reductase of degidrofoliyevy acid and suppress formation of the tetrahydrofolic acid participating in biosynthesis of purines.
• Alkylating agents, interacting with DNA, block cell fission.
• Antibiotics. The pharmacological effect of many antibiotics is based on RNA synthesis suppression. Cyclosporine, Actinomycinums of D and S, puromycin, chloramphenicol have similar properties.