Exam II - Tissue Transplantation and Rejection

Transplantation

the only form of treatment for end-stage organ failure. Serves as an important tool for understanding immunological mechanisms

70%

percent genetic matching or greater that is ideal for tissue or organ transplantation

genetic disparity

The barrier to transplantation is the _____between the donor and recipient

Immunosuppressive drugs

drugs that are used in order to allow for widespread practice of successful transplantation. Minimize the chances of a transplant rejection

Autograft

transplantation performed within an individual. Ie) skin graft

Isografts/syngeneic grafts

grafts performed between genetically identical individuals. Ie) between monozygotic twins

Allograft

transplantation performed between two members of the same species who are not genetically identical

Xenotransplantation

transplantation of tissue or organs between different species.

Xenogeneic barrier

formed by antigenic differences between the donor and recipient during xenotransplantation of tissues or organs between different species.

Allogenic (Antigenic) differences

differences in donor versus recipient genetics which result in an immune response to transplants occurring between individuals of the same species who are not genetically identical. Does not occur for autographs or isografts

Direct allorecognition

interaction where a recipient T cell receptor (CD4 or CD8) binds a donor MHC molecule bearing the donor peptide.

Indirect allorecognition

interaction where a recipient T cell receptor (CD4) recognizes a donor MHC molecule that has been processed by a recipient APC and presented as a peptide. Occurs when the number of donor-derived antigen presenting cells is no longer high enough to stimulate a direct immune response. Is seen in chronic rejection. Ie) in the cornea which lacks larger numbers of APCs

Host versus graft response

host immune system responds to and attacks donor tissue. Main causative factor is by differences in MHC molecule allotypes. Host's responses show memory for MHC molecules found on grafts, so subsequent grafts will be rejected more rapidly. Can occur for other gene loci as well, but at slower rates.

MHC molecules

molecules expressed by all nucleated cells. Interacts with host's T cells to cause a host immune response against a graft.

faster

is T cell response to grafts faster or slower than their response for a pathogen?

Histocompatibility antigens

major targets for transplantation rejection. Ie) MHC molecules which are highly polymorphic

Minor antigens

targets for transplantation rejection even when the donor and recipient MHCs are identical. Nature of this rejection mechanism is mostly unknown.

H-Y system

antigens encoded by the Y chromosome being only expressed on male cells. The best studied minor histocompatibility antigen system. Ie) grafts from female mice are always accepted. Grafts from male mice to other males are accepted. Grafts from male mice to females are rejected.

Donor lymphocytes

these cells can attack the graft recipient in a graft versus host reaction. They produce an immune response against recipient MHCs or minor histocompatibility antigens. Ie) bone marrow transplantation

Graft versus host disease

condition caused by immunocompetent cells of the donor reacting against their immunosuppressed host animal. Often leads to death of the recipient. Avoid by careful donor matching, removal of T cells from grafts, and immunosuppression of the graft tissue.

Hyperacute rejection

mechanism of graft rejection where there is an immediate immune response by the host mediated by pre-existing antibodies which bind to endothelial cells. Can occur due to previous transplants, blood transfusions, or pregnancy and occurs within minutes. Ie) xenotransplant between a big and a primate

Acute rejection

graft rejection occurring over the span of days to weeks, due to activation of alloreactive T cells.

Chronic rejection

graft rejection occurring over the span of months to years. Ie) corneal transplant because it is avascular the immune response is slower

complement activation

Hyperacute rejection can result in extensive necrosis of blood vessels mediated by...

necrosis of blood vessels, intersititial hemorrhage, blood coagulation

three consequences of a hyperacute rejection

Cross matching

method where donor leukocytes are incubated with recipient serum in the presence of complement. If cell death occurs, the recipient should not receive this particular donor's tissue or organ. Performed prior to surgery to evaluate the likelihood of transplant rejection.

thymidine

Nucleoside that can be assayed to determine T-Cell Proliferation. Levels its levels will be higher during an (allogenic or autologous) transplantation, indiciating an immune response to the transplantanted tissue