Transplantation Objectives Flashcards
Autograft –>
grafts from self (i.e skin graft)
Isograft/homograft –>
grafts between identical twins
Allograft –>
Transplant between members of the same species
Xenograft –>
grafts across species
What is graft rejection?
because a graft is foreign, the host’s immune system will attempt to eliminate this intruder.
hyperacute (delayed hyperacute), acute, chronic based on the time over which the rejection process develops and the treatment options available
Explain hyperacute graft rejection
Preformed antibodies (patient immunized) against antigens on the donor tissue Results in complement activation, endothelial damage and inflammation and thrombosis
tx: graft removal
Explain a hyperacute graft rejection when a xenograft is used
existence of natural antibodies in man to carbs presented on the transplanted pig organs
Explain Acute graft rejection
Most common type of allograft rejection occurring in the early period post transplantation (weeks)
recognition by, and activation of, naive T cells on parenchymal and endothelial cells.
causing immune cell infiltration and/or inflammation.
tx: immunosuppressive therapy
Explain chronic graft rejection
rejection occurring weeks, months, or years after transplantation
release of non specific growth factor like mediators (fibroblast or endothelial growth factor) which causes hyperproliferation of connective tissue and mesenchymal cells
tx: immunosuppressive therapy
Many immune cells are activated in graft rejection. Despite this, therapies aimed at acceptance of a graft are primarily based on inhibition of CD4+ Th1 cells. Why?
During a graft rejection chemokines and cytokines are secreted by the graft (Donor) cells and enter circulation.
These cytokines either alter vascular permeability or express adhesion molecules/activate them to high affinity on circulating leukocytes.
This leads to extravasation of T cells, monocytes and neutrophils into the graft where Class II MHC alloreactive CD4+ T cells are activatived and differentiate primarily to Th1 cells.
what is Graft versus host disease (GVHD)
Donor CD4+ and CD8+ T cell activation via Class I and Class II MHC presentation by recipient cells
Immunosuppressed recipient cannot initiate counterattack –> Donor T cells initiate rejection in host tissue
Common with bone marrow, intestinal and liver transplant
what are some symptoms/presentation with GVHD?
Chronic inflammatory attacks on various tissues results in altered permeability, cell and fluid migration
Skin sloughing, diarrhea, inflammation of lungs, kidneys and liver.
What are some treatment options for patients with GVHD?
Removal of all donor T cells and infusion of IL-3 and GM-CSF before transplant, immunosuppression
Explain the defect in G vs. L ( graft versus leukemia effect)
Same T cell reaction as GVHD except specifically directed at recipient leukemia cells
Occurs with bone marrow transplant in leukemia patients
Graft vs. Minor Histocompatibility
Are there any treatments for G vs. L?
nope
What is the problem with intestinal transplants (GVHD)(Crohn’s disease rx)
CMV virus infection common in acute rejection –> since immunosuppressed= serum Ig levels normal but T cell activity reduced
symptoms are weeping rash, cramps, and fever
Corneal transplants, prognosis
Patients survive without immunosuppressive drugs, because the foreign antigens expressed by the graft are not seen by host cells
Heart transplants, prognosis
88% of patients survive at least a year post transplant.
problem? high incidence of atherosclerotic disease in recipients occurring in years following transplant
Liver transplant, prognosis
resistant to rejection once any early acute rejection episodes pass, and long term graft survival is similar
80% of patients survive at least a year
Kidney transplant, prognosis
90% after one year.
required to take immunosuppressive drugs for the rest of their lives
pancreas transplant, prognosis
patients survive optimally if given into the portal vein
Bone transplant, prognosis
provide an inert scaffold for patients to bridge the time to replace allogenic tissue with host bone matrix.
What are three potential problems of immunosuppression for transplant patients?
1) increased risk for infection
2) increased risk for malignancy
3) cardiovascular risks may also be increases with some of the immunosuppression drugs
In the absence of immunosuppression what happens?
transplanted tissue will be rejected by the host
