_TRANSPLANTATION
_ Types of Grafts (Transplants)
1. Isograft or Syngraft. It involves transfer of tissue between genetically identical twins. There is no immune response.
2. Autograft is a graft removed from one site and placed to another site in the same individual. There is no immune response as the tissue is 'self'.
3. Allograft or homograft. It involves transfer of tissue between genetically different individuals of the same species.
TRANSPLANT REJECTION
Rejection is usually with allografts. The major transplantation antigens of HLA system are responsible for rejection.
Mechanisms of Graft Rejection- Types
Transplant rejection involves several hypersensitivity reactions. It depends on recognition by the host of the grafted tissue as foreign. The antigens are those of HLA (major histocompatibility antigen) system. Both T cells and antibodies play a role. T cells are pivotal in the rejection of organ transplants. Antibodies against alloantigens can also mediate rejection.
I. T cell-mediated Reactions. Both CD4 helper cells and CD8 CTL are involved. Two pathways have been proposed for the reactions :
A. Direct Pathway. Antigen-presenting cell is the dendritic cells in the graft of the donor. Important immunogens are the class I and II HLA molecules on dendritic cells. They also possess costimulatory B7 molecules. Donor class II and class I antigens along with B7 molecules are recognized by CD4+ helper T cells and CD8+ cytotoxic T cells respectively. Th1 cells are activated by class It HLA antigens leading to proliferation of these cells and release of IL-2 from these cells. IL-2 augments the proliferation of CD4+ cells. Th-1 cells leads to induction of a local delayed hypersensitivity reaction.
Th1 type CD4+ helper cells provide helper signals IL-2 for the differentiation of class I specific CD8+ cytotoxic cells. Mechanisms to destroy the graft : (1) lysis of cells that bear class I antigens by cytotoxic T cells (CD8+), and (2) nonspecific damage by macrophages and other cells of the delayed hypersensitivity reaction.
1. Isograft or Syngraft. It involves transfer of tissue between genetically identical twins. There is no immune response.
2. Autograft is a graft removed from one site and placed to another site in the same individual. There is no immune response as the tissue is 'self'.
3. Allograft or homograft. It involves transfer of tissue between genetically different individuals of the same species.
TRANSPLANT REJECTION
Rejection is usually with allografts. The major transplantation antigens of HLA system are responsible for rejection.
Mechanisms of Graft Rejection- Types
Transplant rejection involves several hypersensitivity reactions. It depends on recognition by the host of the grafted tissue as foreign. The antigens are those of HLA (major histocompatibility antigen) system. Both T cells and antibodies play a role. T cells are pivotal in the rejection of organ transplants. Antibodies against alloantigens can also mediate rejection.
I. T cell-mediated Reactions. Both CD4 helper cells and CD8 CTL are involved. Two pathways have been proposed for the reactions :
A. Direct Pathway. Antigen-presenting cell is the dendritic cells in the graft of the donor. Important immunogens are the class I and II HLA molecules on dendritic cells. They also possess costimulatory B7 molecules. Donor class II and class I antigens along with B7 molecules are recognized by CD4+ helper T cells and CD8+ cytotoxic T cells respectively. Th1 cells are activated by class It HLA antigens leading to proliferation of these cells and release of IL-2 from these cells. IL-2 augments the proliferation of CD4+ cells. Th-1 cells leads to induction of a local delayed hypersensitivity reaction.
Th1 type CD4+ helper cells provide helper signals IL-2 for the differentiation of class I specific CD8+ cytotoxic cells. Mechanisms to destroy the graft : (1) lysis of cells that bear class I antigens by cytotoxic T cells (CD8+), and (2) nonspecific damage by macrophages and other cells of the delayed hypersensitivity reaction.
_B. Indirect Pathway. Recipient's own antigen-presenting
cells present allogenic class I and class II
HLA antigens of the graft of the
donor. Recipient's T lymphocytes recognize these antigens from the donor
tissue.
II. Antibody-Mediated Reactions. Antibody- mediated reactions can take two forms :
1. Hyperacute rejection.It occurs when preformed antidonor antibodies are present in the circulation of the recipient. Such antibodies may be present in (a) Prior blood transfusions from HLA-nonidentical donors. Platelets and white cells are rich in HLA antigens, (b) Multiparous women who develop anti-HLA antibodies against paternal antigens shed from the fetus, (c) A recipient who has already rejected a transplant. Rejection occurs immediately by Arthus-type reaction. Practically this is not seen now due to cross-matching of donor's lymphocytes with recipient's serum.
2. Antigraft antibodies produced by sensitized B cells on exposure to class I and class II HLA antigens of the donor. Activation of Th2 type CD4+ cells generate IL-4 and IL-5 that promote B cell proliferation and differentiation.
Graft vasculature is mainly affected by complement dependent cytotoxicity, ADCC and antigen-antibody complexes leading to rejection vasculitis.
II. Antibody-Mediated Reactions. Antibody- mediated reactions can take two forms :
1. Hyperacute rejection.It occurs when preformed antidonor antibodies are present in the circulation of the recipient. Such antibodies may be present in (a) Prior blood transfusions from HLA-nonidentical donors. Platelets and white cells are rich in HLA antigens, (b) Multiparous women who develop anti-HLA antibodies against paternal antigens shed from the fetus, (c) A recipient who has already rejected a transplant. Rejection occurs immediately by Arthus-type reaction. Practically this is not seen now due to cross-matching of donor's lymphocytes with recipient's serum.
2. Antigraft antibodies produced by sensitized B cells on exposure to class I and class II HLA antigens of the donor. Activation of Th2 type CD4+ cells generate IL-4 and IL-5 that promote B cell proliferation and differentiation.
Graft vasculature is mainly affected by complement dependent cytotoxicity, ADCC and antigen-antibody complexes leading to rejection vasculitis.
Morphology of Rejection Reactions
Rejection reactions are classified as hyperacute, acute, and chronic.
1. Hyperacute rejection. It occurs within minutes or hours after transplantation. The histological reactions are Arthus-type reaction. Neutrophils accumulate rapidly. Immunogiobulins and complement are deposited in the vessel wall. Fibrinoid necrosis occurs in arterial walls. Microthrombosis may lead to severe ischaemia and necrosis of the graft.
2. Acute rejection. The reaction occurs usually within days but may appear months or even years later. Both cellular and humoral tissue injuries play part.
(a) Acute cellular reaction is marked by an interstitial intense mononuclear cell infiltrate. Both CD4+ and CD8+ lymphocytes are present.
(b) Acute humoral rejection is evident as acute rejection vasculitis. It is mediated primarily by antidonor antibodies. There may be necrotizing vasculitis, neutrophilic infiltration, deposition of immunoglobulins, complement and fibrin; and thrombosis. Necrosis of parenchyma may occur.
3. Chronic rejection occurs months or years later due to ischaemic changes as a result of arterial narrowing.
Checking of Compatibility to prevent rejection:
Compatibility of donor and recipient must be determined before transplantation to prevent or minimize rejection. The following tests are done :
1. ABO blood group compatibility.
2. HLA antigens by tissue typing.
3. Cross-matching between recipient's serum for preformed antibodies against donor's HLA antigens. Donor's lymphocytes are used.
Immunosuppressive therapy
Immunosuppressive therapy is given to the recipient to reduce the chance of rejection of transplanted tissue. These are cyclosporine, tacrolimus, corticosteroids, azathioprine, monoclonal antibodies and radiation.
Immunosuppressive therapy increases the recipient's susceptibility to opportunistic infection and neoplasm. Common opportunists are: Cytomegalovirus, varicella zoster virus, herpes simplex virus, Pneumocystis carinii, and Aspergillus spp., Gram-negative rods.
These patients are at increased risk for developing lymphomas, squamous cell carcinoma, and Kaposi's sarcoma.
Rejection reactions are classified as hyperacute, acute, and chronic.
1. Hyperacute rejection. It occurs within minutes or hours after transplantation. The histological reactions are Arthus-type reaction. Neutrophils accumulate rapidly. Immunogiobulins and complement are deposited in the vessel wall. Fibrinoid necrosis occurs in arterial walls. Microthrombosis may lead to severe ischaemia and necrosis of the graft.
2. Acute rejection. The reaction occurs usually within days but may appear months or even years later. Both cellular and humoral tissue injuries play part.
(a) Acute cellular reaction is marked by an interstitial intense mononuclear cell infiltrate. Both CD4+ and CD8+ lymphocytes are present.
(b) Acute humoral rejection is evident as acute rejection vasculitis. It is mediated primarily by antidonor antibodies. There may be necrotizing vasculitis, neutrophilic infiltration, deposition of immunoglobulins, complement and fibrin; and thrombosis. Necrosis of parenchyma may occur.
3. Chronic rejection occurs months or years later due to ischaemic changes as a result of arterial narrowing.
Checking of Compatibility to prevent rejection:
Compatibility of donor and recipient must be determined before transplantation to prevent or minimize rejection. The following tests are done :
1. ABO blood group compatibility.
2. HLA antigens by tissue typing.
3. Cross-matching between recipient's serum for preformed antibodies against donor's HLA antigens. Donor's lymphocytes are used.
Immunosuppressive therapy
Immunosuppressive therapy is given to the recipient to reduce the chance of rejection of transplanted tissue. These are cyclosporine, tacrolimus, corticosteroids, azathioprine, monoclonal antibodies and radiation.
Immunosuppressive therapy increases the recipient's susceptibility to opportunistic infection and neoplasm. Common opportunists are: Cytomegalovirus, varicella zoster virus, herpes simplex virus, Pneumocystis carinii, and Aspergillus spp., Gram-negative rods.
These patients are at increased risk for developing lymphomas, squamous cell carcinoma, and Kaposi's sarcoma.