Introduction to Transplantation Immunology Flashcards
syngenic
transplantation between genetically identical individuals
allogenic
transplantation between genetically dissimilar individuals of same species
xenogeneic
transplantation between different species
minor histocompatability antigen
normal proteins on cell surface that are polymorphic in nature
evidence that graft rejection is caused by lymphocytes
occurs 7-14 days after first transplant
-role of lymphocytes
rejection occurs more rapidly second time
-role of memory
rejection of distinct graft 7-14 days
-specific response
evidence for role of MHC in grafts?
transplant between genetically identical individuals not rejected
transplant between genetically non-identical individuals is rejected
direct alloantigen recognition
allogenic APC presents allogenic MHC
**activates CTLs
indirect alloantigen recognition
self APCs present allogenic MHC proteins
**activates CD4 T cells
can also have allo-antibodies produced by alloreactive B cells in indirect pathway
high probability that T cells recognize allogenic MHC due to?
T cells are selected to have low affinity
-allogenic MHC not negatively selected - may be high affinity
self MHC restricted T cells are able to recognize foreign MHC
allogenic MHC with bound peptide may mimic self MHC and peptide complex
what trigger costimulation expression in transplantation patients?
fuck
hyperacute rejections
within minutes
thrombosis of graft vessels followed by ischemic necrosis
host circulating antibodies are specific for antigens on graft endothelial cells
complement activation leads to endothelial cell injury
thrombosis and vascular occlusion occur
how to prevent hyperacute?
cross-match with antibodies
acute rejection
within days to weeks
rejection timulated by alloantigens in the graft
mechanism:
- acute cellular rejection (CTL and CD4)
- microvascular endothelialitis
- acute antibody-mediated rejection characterized by transmural necrosis of graft vessel walls
acute rejection treatable?
YES!
chronic rejection
months to years after transplant
T cells and antibodies against alloantigens
immune response results in fibrosis of graft tissue and gradual narrowing of vessels
-graft arteriosclerosis
immunosuppressive drugs for T cells used in transplantation
azathioprine, rapamycin, cyclosporine, anti-IL-2R, anti-TCR (OKT3, thymoglobulin)
rapamycin
targets mTORC1
azathioprine
no proliferation
cyclosporine
inhibits calcineurin
important one**
CTLA4-Ig
inhibits CD28 B7 interaction
thymoglobulin, OKT3
no TCR activation
side effects of immunosuppression
malignancy
infections
drug toxicity
non T cell targets for immunosuppression
alloantibodies and alloreactive B cells
anti-inflammatory drugs
inhibitors of leukocyte migration
strategy to minimize alloantigenic effects?
cross-matching
-testing for preformed antibodies against donor HLA
why do people develop anti-A and anti-B antibodies for blood group antigens?
normal gut flora has similar epitopes
lewis antigen
fucosylation at additional terminal sites of blood group antigen
rhesus antigen
Rh
15% of population has deletion or other alteration in RHd allele
Can ABO-incompatible transplant be done?
???/
GVHD
graft versus host disease
reaction of mature grafted T cells to alloantigens of the host
usually against minor histocompatability antigens
acute less than 100 days
chronic greater than 100 days
treated by immunosuppression
hematopoietic stem cell transplant
transfer allogenic pluripotent hematopoietic stem cells
patient treated with radiation to deplete bone marrow
