Transplantation Immunology Flashcards
Transplantation
potentially lifesaving treatment for endstage organ failure, cancers, autoimmune diseases, immune deficiencies etc
Transplantation Immunology
sequence of events that occurs after an allograft or xenograft is removed from donor & then transplanted into a recipient
Organ Transplants
introduce foreign tissues/cells into a host
immune system still intact!
Hematopoietic cell Transplant
replacement of all blood/marrow cells
immune system is first depleted !
Autologous grafts (autografts)
self-tissue transferred from one body site to another in the same individual
ex: skin graft on a burn patient
Syngenetic gratfts (isografts)
tissue transferred between genetically identical individuals
Allogeneic grafts (allografts)
tissue transferred between genetically different members of the same species
most transplants
Xenogeneic grafts (Xenografts)
tissue transferred between different species
pig heart valves
Transplant Complications
- Hyperacute rejection
- Acute cellular rejection
- Chronic rejection
Hyperacute Rejection
occurs w/in minutes to hours after vascular supply to the transplanted organ is established
ABO, HLA antigens elicit the reaction - leads to necrosis of the tissue
this is seldom encountered due to testing
Crossmatching
tests a recipient’s serum against prospective donor’s cells (WBCs) to determine if donor specific antibodies (DSAs) are present
Acute Transplant Rejection
develop days to weeks after transplant
cellular type rejection involving CD8+ T cells ( Type IV delayed hypersensitivity)
Chronic Rejection
slow but continual loss of organ function over months or years
multi-factorial
most transplanted organs will be rejected in time
Testing for Chronic Rejection
screen for antibodies in the serum against HLA class 1 & 2 proteins key reagent - latex beads coated with various class 1 or 2 antigens
Hematopoietic Cell Transplant
most difficult
entire immune system is transferred
autologous transplant is best if malignancy doesn’t involve bone more or is not genetic
3 sources of Hematopoietic Stem Cells
bone marrow
peripheral blood after ‘mobilization’
umbilical cord
HCT processing
- collection of stem cells from bone marrow or peripheral blood
- processing - isolate, concentrate & prepare stem cells for storage
- cryopreservation
- chemotherapy
- infusion of stem cells
Neutrophil Engraftment
usually occurs within 14-20 days
absolute neutrophil count of 500/ul for 3 days in a row
Platelet engraftment
20,000 platelets/ul
occurs after neutrophil engraftment
can take up to 2 months
Graft Versus Host Disease (GVHD)
the infused products often contain some mature T cells which target the recipient (>90% mortality rate)
Infections prior to neutrophil engraftment
viridens strep, enterococcus, enterobacteriaceae
2% due to Candida - high mortality rate
Immunosuppressive agents
corticosteroids
IL-2 signaling blockers (Cyclosporin A, Tacrolimus, Everolimus)
BK Virus
important cause of Kidney transplant failure (5-8%)
90% are infected by adulthood (asymptomatically)
re-emerges due to immune suppression
