Chapter 17 - Transplants Flashcards
MATCHING:
1) autografts a) grafts exchanged b/w nonidentical members same sp.
2) isografts b) grafts exchanged b/w members of diff. species
3) allografts c) grafts exchanged from 1 part to another same body
4) xenografts d) grafts exchanged b/w identical twins
1 - c
2 - d
3 - a
4 - b
Graft rejection shows what 2 key features of adaptive immunity?
memory and specificity
what is graft rejection mediated by?
lymphocytes / T lymphocytes
what is common to all T-cells?
CD3
what HLAs are strong barriers to transplantation?
class I (HLA-A, HLA-B)
what are the 3 most important HLAs for transplantation?
class II (HLA-DP, HLA-DQ, HLA-DR)
remember it’s alphabetical p, q, r
in direct allorecognition, what does the T cell recognize?
what is it involved in?
UNPROCESSED allogeneic MHC from APC
primary response against graft
in indirect allorecognition what does the T-cell recognize?
when is this important?
PROCESSED peptide of allogeneic MHC molecule bound to self MHC or Professional APC
during chronic rejection when # of donor prof. APCs is low
what are the types of rejections in order from least time to most time taken
hyperacute, accelerated, acute, chronic
what is the cause of hyperacute rejection?
preformed antidonor Abs and complement
what is the cause of accelerated and acute rejection?
reactivation of sensitized T cells
primary activation of naive T cells
what is the cause of chronic rejection?
immunologic and nonimmunologic factors
Acute cellular rejection involves what?
Th1 cells
Acute vascular rejection involves what?
Th2 (humoral)
what kind of response does hyperacute rejection involve?
Humoral response
what is an example of hyperacute rejection?
what does it activate?
ABO blood group incompatibility
classical complement activation leading to death of epithelium
what is an example of acute rejection?
what kind of cell damage is present? by what?
CD4 and CD8 T cells occurs in days to weeks
parenchymal cell damage, interstitial inflammation, endothelialitis
by CTLs and DHT reactions
what plays an important role in triggering acute rejection?
Donor DCs (aka passenger leukocytes)
what is an example of chronic graft rejection?
what is involved and what pathway is the main pathogenic mech?
months to years after transplantation due to ischemia of the organ
macrophages and Abs involved, main mech is Indirect pathway
what are some non-immunological factors in chronic rejection?
does chronic rejection respond to immunosuppressive therapy?
ischemia-reperfusion damage, recurrence of the disease, nephrotoxic drugs
NO
what variables determine transplant outcome?
condition of the allograft (non-immunological factors)
donor-host Ag disparity
strength of host anti-donor response
immunosuppressive regimen
when transplanted, damaged graft tissues release mediators which trigger several biochemical cascades leading to what?
immediate tissue damage via a clotting cascade generates fibrin and fibrinopeptides
what do fibrinopeptides do?
increase local vascular permeability and serve as chemoattractant for neutrophils and macrophages
what does the kinin cascade produce?
what do early proinflammatory responses lead to if left uncontrolled?
bradykinin which causes vasodilation, smooth muscle contraction, and increased vascular permeability
allograft rejection
what is included in the donor - recipient work up?
ABO blood group compatibility, tissue typing (HLA), cross-matching (presence of preformed Abs), mixed lymphocyte reaction
ABO matching is NOT important for what?
corneal transplantation, heart valve transplantation, bone and tendon grafts
why is HLA compatibility between donor and recipient required?
due to extreme polymorphism of HLA
the ID of HLA Ags has traditionally been done by what mechanism?
complement dependent serology
what are the sources of lymphocytes for HLA typing?
spleen and LN from cadaver
what doe the Ag-Ab complex activate?
classical complement cascade resulting in lymphocyte lysis which can be detected by staining the cells
what is cross matching needed for?
to prevent hyperactive Ab-dependent rejection of graft
how do you test for preformed Abs?
use a microcytotoxicity test with complement-activated cell damage
the recipient’s serum is mixed with donor cells, if no damage then could be a donor
what is the process of the mixed lymphocyte response test?
leukocytes from 2 unrelated individuals are mixed, lymphocytes from the donor are irradiated to stop their proliferation and called stimulator cells
what are stimulator cells used for?
what are responder cells?
presentation of class II MHC Ags
intact lymphocytes from the recipient
how are responder cells activated?
how is the response measured?
by mismatched class II MHC and proliferate
tritiated thymidine
If class II MHC Ags are the same ______?
no proliferation will occur (good for transplantation)
what happens in HVG response?
host immune system (T cells) attacks the donor tissue (transplant)
adaptive immune response
Is the immune response against a graft stronger or weaker than the response against a pathogen?
why?
much stronger because of a higher frequency of T cells that recognize graft as foreign
What activates endothelial cells and what enters?
Non-immune injury of the graft (Danger Signals)
T cells enter the allograft
what are the effector mechanisms of graft rejection?
Humoral rejection Th2
Cellular rejection Th1
what happens in GVHD?
who does it happen to?
reaction of grafted mature T cells in the marrow inoculums with allo-Ags of the host directed against minor H Ags or recipient
immunocompromised recipients due to their inability to reject the allogenic cells in the graft
where does GVHD occur most often?
small bowel, lung, liver
What happens in acute GVHD?
what are clinical manifestations?
epithelial cell death in the skin, liver, and GI
rash, jaundice, diarrhea, GI hemorrhage
What happens in chronic GVHD?
what are clinical manifestations?
fibrosis and atrophy of organ
organ dysfunction, obliteration of small airways
What are the 3 immunologically privileged sites?
brain, testis, cornea (eye)
