Transplant Flashcards
syngeneic transplant
transplant between genetically identical individuals
allogenic transplant
transplant between non identical individuals of same species
autograft
transplant from self…like skin graft
allogeneic hepatopoietic stem cell transplant purpose
to help eradicate a hematologic malignancy through use of immune cells from donor that can target the cancer
two types of Stem cell transplants with greater risk of relapse
syngeneic and T cell depleted
both increase risk about 3 fold
what are chanced of sibling being a HLA match with a patient?
about 1/4
how much do kids match parents in HLA?
1/2 match
What is rule of thumb when looking for a match?
want to match 12/12 HLA alleles, but if cannot get that then you get less matching likely 11/12 and will need to use some degree of T cell depletion in therapy
can you give SCT across ABO blood types?
yes because can deplete donor plasma or RBCs so nothing to react with
GVHD acute symptoms and onset
rash, colon and liver issues
first three months after SCT
Chronic GVHD symptoms and onset
skin, eyes GI and liver mainly
6 months after SCT
medication treatment for GVHD
inhibitors of T cell activation like tacrolimus, cyclosporin, and sirolimus
inhibitors of T cell proliferation like methotrexate
and T cell depleting antibody like Anti thymocyte globulin
reason for problems with matched HLAs in GVHD?
can have many minor mismatches for proteins, especially when donor is homozygous for a protein and recepient is heterozygous…leads to unfamiliar proteins the donor T cells may recognize
6 rules for matching for SCT
12/12 HLA match
prefer related matches over unrelated matches…less miHA
male preferred because alloreactivity of mother from pregnancy and Y antigens
stem cell source…bone marrow or blood?
CMV negative with CMV negative and CMV + then not important
ABO match preferred
mediator of the graft rejection for solid organ transplant?
will always have some form of HLA/peptide rejection.. immunosupression is needed
problem with blood transfusions in organ transplant?
previous transfusions can have allowed patient to make antibodies against specific HLA forms so if they have those antibodies then any organ with that HLA cannot be used
hyperacute graft rejection characteristics
from ABO antibodies or circulating anti-HLA antibodies
occurs within hours, leads to immune complexes and complement fixation, vascular damage and thrombosis
direct allorecognition characteristics
when T cells of recipient will interact with APCs from donor that are presenting peptides and an unfamiliar HLA complex…this goes down as you lose donor APCs
mainly a CD8 cytotoxic response from recipient against the donor
indirect allorecognition characteristics
recipient APC digests donor protein and presents on recipient HLA and this can lead to stimulation of a CD4 cell response
acute rejection of graft and type of hyper
1-3 weeks after transplant…cell mediated toxicity and humoral graft rejection
type IV mainly
chronic rejection of graft characteristics and type of hyper
more than 3 weeks post transplant…fibrosis of vessels can lead to ischemia of organ
mononuclear cells involved…
CD4 cells secrete cytokines that recruit APCs like macrophages
type II and IV
rejection prevention meds with solid organs
steroids
DNA replication inhibitors (azathioprine and mycophenolate)
Inhibitors of T cell activation (cyclosporine, tacrolimus, sirolimus)
lymphocyte depleting antibodies (antithymocyte globulin, rituximab, alemtuzumab (CD52 target))
