Lecture 26: Transplantation and Transfusions Flashcards
______polymorphism is the reason why organisms can respond to many antigens but also the reason why it can be hard to find a suitable donor
MHC
MHC class ____ is found on all nucleated cells & presents endogeonous antigens to CD8 Tcells
MHC Class I
MHC class ____ are found on APCs and present exogenous antigens to CD4 T cells
MHC Class II
MHC class _____ are associated w/ complement proteins and other genes
class III
transplantation of tissue b/w sites WITHIN one individual
Autograft
skin graft to cover a wound
no rejection
transplantation of itssue from a genetically identical individual
Isograft
organ transplant from identical twin
transplant of tissue from a member of the same species
Allograft
typically organ transplant b/w genetically distinct individuals
rejection within 1-2 weeks
Xenograft
transplant of tissue from member of diff species
rejection within hours
ethical concerns
pathogen transfer
without _____, all grafts except autographs will eventually be destroyed
immunosuppression
characteristics of transplant rejection
- immune responses against donor MHC
- involved cellular and humoral components
- loss of transplanted organ
donated tissues contain” _____” leukocytes
passenger
may migrate out of tissue
hyperactue rejection occurs within______hours
48
accelerated rejection occurs in up to _____days
7
acute rejection occurs after _____ days
7
chronic rejection occurs after…
several months up to years
in acute rejection, MHC incompatability triggers
T recc response
in acute rejection, RBC antigen incompatability triggers
Antibody response
Pathophysiology of acute rejections
- MHC and RBC antigen incompatability
- cytotoxic T cell infiltration
- Damage to endothelial cells
- thrombosis of vessels
- loss of blood supply to organ
- can be exacerbated by surgical trauma
in acute rejection, DC cells present antigen to Th1 cells which then secrete ______ and activate_______
secrete IL-2 & INF-y
activate cytotoxic T cells and NK cells
Cytotoxic T cells respond to
foreign proteins
NK cells produce ____and _____
INFy and TNF-a
TNF-a activates effector cells (macs,NKs)
blood group antigens stimulate ______cells causing antibody production…“natural” antibodies can cause hyperacute rxn
Th2
what are the 2 pathways of rejection
Direct pathway (occurs early/accute)
Indirect pathway (occurs later/chronic)
Direct pathway rejection
- recipient T cells enter graft and respond to foregin MHC on donor cells
- T cells attack graft vascular endothelium
- vessel destruction + thrombosis
indirect pathway rejection
- processing of graft antigens by host DCs
- generation of cytotoxic T cells
- NK cells contribute
what are the immune privileged sites
eyes, thymus, testes, brain
how is inflammation controlled in immune priviledged sites
- BBB, impermeable tissue
- no DCs
- low MHC expression
- immunosuppressive molecules (IDO, TGF-B, neuropeptides, complement inhibitors, CD95L)
In graft vs host disease (GVHD) cells from the graft attack the _____
host
effects of MHC class I mediated GVHD
- bone marrow destruction
- mucosal destruction
- liver dz
- TH1 cytokines
effects of MHC class II mediated GVHD
- autoantibodies (lupus like syndrome)
- treatment w/ Anti IL-4 antibody
dog erythrocyte antigen _____ is most antigenic
1 (DEA 1)
includes 1.1, 1.2 +/- subtypes
“universal” canine donor
negative for DEAs 1.1, 1.2, 3,5,7
positive for DEA 4
Blood antigens ___ and ____ are most antigenic in horses
Aa and Qa
QH or standardbred gelding are most likely to be Aa-Qa
gelding of same breed as patient is next best option
what is a major cross match
serum from recipient, RBCs from donor
what is a minor cross match
RBCs from recipient, serum from donor
what is equine neonatal isoerythrolysis
mare of foal has antibodies to paternal RBC antigens that get passed to foal in colostrum, causing hemolytic disease in foal
- very common in mule foals
- can be tested for pre-partum
- prevent foal from nuring for 24 hrs, strip colotrium or provide alternative colostrum
examples of immunosuppressive molecules found in immune privileged sites
IDO
TGF-B
neuropeptides
complement inhibitors
CD95L
