Chapter 17: Transplantation and Immune Reponses

Blood Transfusion

involves the transfer of blood cells or blood-cell components from one individual (donor) to another (recipient)

Solid Organ Transplantation

involves transfer of a donor organ into a patient whose own organ has failed to function properly or has been damaged irreparably

Autograft

transplantation of tissue from one area on an individual to a different area on the same individual

Isograft

tissue transplantation between genetically identical individuals

Allograft

tissue transplantation between genetically distinct individuals

Xenograft

tissue transplantation between different species

Alloreactions: HLA Polymorphisms

polymorphisms in HLA molecules can lead to alloreactions following solid organ and hematopoietic stem cell transplantations e.g. solid organ rejection and graft vs host disease

Solid Organ Rejection

recipient’s adaptive immune system recognizes the transplant as foreign, inducing a response that results in rejection and destruction of the donor organ/tissue

Graft-versus-Host Disease

newly transplanted hematopoietic system recognizes recipient’s tissues and organs as non-self and targets them in an immune response; recipient dendritic cells present alloantigens derived from recipient organs and tissues to mature donor T cells present within transplanted bone marrow

Hyperacute Rejection

caused by preexisting antibodies in the recipient that bind to blood antigens or HLA molecules expressed on blood vessels within transplanted tissue; mirrors a type II hypersensitivity reaction; preventable by proper blood type matching HLA typing/crossmatching

Hyperacute Rejection: Transplanted Tissue

destruction of vascular endothelial cells through complement activation via classical pathway and inflammation prevent proper oxygenation of transplanted organ

Acute Rejection

caused by recognition of donor MHC-peptide complexes presented by donor dendritic cells to recipient T cells; mirrors a type IV hypersensitivity reaction; preventable by proper HLA typing and crossmatching and use of immunosuppresssive drugs

Acute Rejection: Effector Mechanism

cytotoxic CD8 T cell activity against donot cells, activation of alloreactive B cells, and antibody dependent cell-mediated cytotoxicity by NK cells

Chronic Rejection

occurs months or years later after transplantation and the reason why a transplanted organ ultimately fails; approx. 1/3 of transplanted kidneys fail within 10 years; caused by immune responses that target the vasculature of transplanted organ

Chronic Rejection: Immune Reponses

mirrors type IV hypersensitivity reaction; decreased blood supply (ischemia) and decreased oxygen delivery to the organ eventually leads to failure; requires the processing and presentation of donor antigens by recipient APCs to alloreactive CD4 T cells; immunosuppressivve drugs can’t prevent this

Chronic Graft vs Host Disease

mimics autoimmune disease; targets multiple recipient tissues and organs (e.g. skin, liver, eyes, mouth, lungs, and GI tract); treatable with imunosuppressive drugs

How to Prevent Graft-versus-Host Diseae

proper matching of HLA and minor histocompatibility antigens e.g. H-Y antigens between donor and recipient

Immunosuppressive Drugs

administered after organ transplants to minimize targeting of the organ by the recipient’s immune system and to prolong organ acceptance; transplant patients are maintained on these throughout their life and cannot be completely weaned off them

Immunosuppressive Drugs: Doses

doses of immunosuppressive drugs are tempered to prevent organ rejection while limiting increases in susceptibility to infection