Immunological basis of graft rejection

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Immunological basis of graft rejection:

Immunological basis of graft rejection By: Vishal Thakur

Types of grafts:

Types of grafts Isografts: graft transplanted between two genetically identical individuals(monozygotic twins). Allografts: graft between genetically different members of the same species. Xenografts: graft between animals of different species.

GRAFT REJECTION :

GRAFT REJECTION Rejection of transplanted organs is the main barrier of transplantation today. It occurs as a result of humoral and cell mediated responses by the recipient to specific antigens present in the donor tissue. These antigens are known as major histocompatibility complex (MHC) molecules. In humans, this group of molecules is referred to a human leukocyte antigen (HLA) complex molecules in humans. During the first stage, known as sensitization, lymphocytes are alerted and respond to the foreign MHC molecules. Rapid proliferation occurs in this stage. In the second 'effector' stage, the graft is destroyed by several cellular and molecular mechanisms.

Types of Rejection :

Types of Rejection Hyperacute rejection Acute rejection Chronic rejection. In xenotransplantation there is fourth type called as hyperacute vascular rejection.

Hyperacute Rejection :

Hyperacute Rejection Occurs usually within the first 24 hours after transplantation. Hyperacute rejection is caused by preexisting host antibodies that bind to antigens present in the graft endothelium. Antigen recognition activates the complement system. There is also an influx of neutrophils. Endothelial cells and platelets are also induced to shed lipid particles from their membrane that promote coagulation.The resulting inflammation prevents vascularization of the graft. The graft then suffers irreversible damage from ischemia. 

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Recipients of blood transfusions sometimes develop antibodies to MHC antigens from the transfused blood. If some of these antigens match those in a graft, then hyperacute rejection may result. Multiple pregnancies may also expose the woman to the paternal antigens of the fetus , resulting in the creation of antibodies.

Acute Rejection :

Acute Rejection 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. As they are polymorphic therefore the chance of a perfect match is extremely rare. 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.

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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 or an is highest in the first 3 months after transplantation and is lowered by immunosuppressive agents in maintenance therapy.

Chronic Rejection :

Chronic Rejection Occurs months to years following transplantation. Characterized by graft arterial occlusions, which results from the proliferation of smooth muscle cells and production of collagen by fibroblasts. This process, termed accelerated or graft arteriosclerosis, results in fibrosis which can cause ischemia and cell death. Most recipients must take immunosuppressive drugs for the rest of their lives, and even that may not be enough to combat chronic rejection. alternative therapies such as tissue engineering, tolerance and xenotransplantation attempt to bypass the perils of chronic rejection and rejection overall.

Acute Vascular Rejection :

Acute Vascular Rejection Found during transplantation of xenografts. Occurs 4-8 days after transplantation. Rejection is characterized by endothelial activation and coagulation, causing cell damage, thrombosis and eventual graft rejection. It is suggested that its cause is returning or residual anti-alpha-gal antibodies, which target the alpha-gal antigen found on pigs and other species. Currently even with heavy immunosupression, most pig to primate grafts fail within thirty days due to acute vascular rejection.

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