what are the different types of grafts?
autograft
isograft
allograft
xenograft
autograft
self-tissue grafted to another self area (skin grafts, blood vessels)
isograft
transplant between genetically identical individuals
allograft
tissue transferred between genetically different numbers of the same species
allotypic determinant
an antigenic determinant that varies among members of a species or between different inbread strains of animals (also referred to as an alloantigen); antibodies made against alloantigens are called alloanitbodies
xenograft
tissue transferred between different species
what is histocompatibility?
the degree of recognition and response to donor tissue by the recipient's immune system
the degree of antigenic similarity between donor and recipient
what role do MHC haplotypes play in organ transplantation?
the antigens involved are encoded by up to 40 different loci, but those most responsible loci are found in the major histocompatibility complex
other loci are also involved
what are the reasons that blood transplantation is so simple?
it can be donated with "minimal" impact on the donor
simple, inexpensive, and involves relatively few medical personnel
usually, blood only needs to function in the recipient for a short amount of time; the recipient will eventually make more
erythrocytes DO NOT express MHC
what is the relationship between A/B/O blood types and carbohydrates of commensal bacteria?
antigens A and B, but not O are structurally similar to carbohydrates on the surface of commensal bacteria
people that like "A" or "B" make antibodies against the carbohydrates of the bacteria
what is the Rh factor?
the Rh factor adds another level of complexity
A/B/O/Rh incompatibility stimulates a type II hypersensitivity response, similar to penicillin, but... there are actually 30+ polymorphisms known
what is hyperacute rejection?
antibody mediated rejection
how is hyperacute rejection characterized?
antibodies for A/B RBC antigens are thought to come from cross-reactive oligosaccharides
antibodies against alloantigens may come from past blood transfusions, from past pregnancies, infectious disease
anti-HLA class I antibodies
what is the relevance of major histocompatibility complex?
dendritic cells in the kidney graft are of donor origin
dendritic cells travel in the blood to the spleen where they activate recipient's alloreactive T cells
effector alloreactive T cells leave the spleen and travel in the blood to the grafted allogenic kidney
effector T cells damage and kill the epithelial cells of the kidney, stopping all kidney function
what is the relevance of MHC matching in bone marrow transplantation?
minimize the risk of graft rejection
what is the difference between allogenic transplantation and autologous transplantation?
an autologous transplant uses the patient's own stem cells, while an allogenic transplant uses stem cells from a donor
what kinds of diseases are treated by BMT?
wiskott-aldrich syndrome
franconi's anemia
osteopetrosis
sickle-cell anemia
what is myoablative therapy?
the destruction of previous bone marrow to (1) give new bone marrow the space and opportunity to thrive (2) ensure that the grafted bone marrow won't be rejection (called conditioning)
what is engraftment?
the point at which hemapoietic stem cells have successfully established themselves in the bone marrow and are making new blood cells
what is a chimera?
the HSCs have the donor phenotype and everything else has the recipient phenotype
what is graft vvs. host disease?
because conditioning is so intense, there are very few (in any recipient) T cells to attack donor tissue
however donor T cells can respond to recipient HLA allotypes, the graft rejects the host
GVHD can attack all tissues, but concentrates in the skin, intestines, and liver
how is HLA compatibility related to engraftment?
the best option is an identical twin
the next-best is an HLA-matched sibling
national and international registries
likelihood of a match is still low
umbicial cord blood can be obtained ; rich in HSCs and relatively few alloreactive T cells
engraftment is slower, but less GVHD
what are minor histocompatibility antigens?
in brothers who receive transplant from an HLA-identical sister, the donor's T cells may recognize proteins coded on the Y chromosomes as foreign, termed H-Y antigens
polymorphisms in various autosomal genes can cause minor differences in expressed proteins that can cause reactivity from donor T cells
why is GVHD "good"?
alloreactive T cells are known to make contributions
they subdue the recipient's immune system which facilitates engraftment
they eliminate malignant cells missed by conditioning
what happens if there are no mature T cells in the transplanted bone marrow?
a decrease in alloreactivity leads to increases in relapse
alloreactivity from minor histocompatibility alleles improves outcomes; an HLA-matched sister is considered a better donor than an HLA-matched brother because of H-Y antigens
elimination of tumor cells by alloreactive T cells is called GVL or GVT
what is the relationship between HSC transplant and a solid organ transplant?
approximately 10 % of fraternal twins share blood during gestation
as a result, their HSCs are a chimera (combination) of both genotypes and are therefore tolerant of the other twin's cells
what is the purpose of immunosuppressive durgs?
to reduce the body's immune response
what are general immunotherapies?
lymphoid irradiation: common in bone marrow transplants
azathioprine: methotrexate
prednisone/dexamethasone
rapamycin/cyclosporine
what are specific immunotherapies?
basiliximab (monoclonal antibody for CD25(IL-2R) on T cells)
rituximab (monoclonal antibody for CD20 on B cells)
belatacept (CTLA-4Ig)
what is immune privilege?
characterized by lack of vasculature, both lymphatic vessels and blood vessels
T cells are significantly less likely to become sensitized to various alloantigens
what are some areas of immune privilege?
cartilage
heart valves
eye
cornea
uterus
testes
the brain
the thymus