2-Transplantation Flashcards
autologous graft
from indiv to same indiv
-no chance of rejection
i.e. bone marrow or blood harvested and saved for future like cancer treatment
syngeneic graft
or syngraft
b/t two genetically identical indivs like twins
-not expect rejection (low/none)
allogeneic graft
b/t genetically dissimilar indivs
-most common form of transplant
-anticipate some episode of rejection
xenogeneic graft
or xenograft
b/t members of two diff species like pigs bc organ size similar
-usually to inc longevity for human transplant later
orthotopic vs heterotopic transplants
ortho = normal anatomic location
hetero = placed in anatomically diff site
i.e. heart bypass surgery with saphenous V > coronary A
first set rejection
7-10 days after graft transplanted b/t non identical indivs
aka primary immune resp
second set rejection
graft transplanted AGAIN then rejected in 2-3 days (faster than first set rejection)
aka secondary immune resp
immunologically privileged sites
where allogenic transplant placed w/o risk of rejection
@anterior chamber eye, cornea, testes, brain
via TGF-beta and Fas ligand
sympathetic ophthalmia
immuno privileged sites
one eye damaged by trauma and autoimmune resp to eye proteins threatens the undamaged eye
-removal of damaged eye and immunosuppressive therapy
transplantation laws
- transplants b/t identical twins never rejected
- b/t genetically dissimilar indivs almost always rejected
- grafts from children rejected by either parent bc express antigens seen as foreign
why foreign?
class I and II MHC proteins foreign bc
1. expression is polymorphic- specific set of MHC
2. edu of thymocytes so other MHC foreign
3. prob that two random indivs express same MHC very small
hyperacute rejection
within MINUTES of attaching graft to recipients blood supply
-mediated by pre-existing antibodies > complement
-untreatable but uncommon bc tech now can detect antibodies pre surgery
acute rejection
within ONE MONTH
two types
1. humoral- antibody + complement mediated lysis of graft = necrosis of blood vessel
2. cellular-cell mediated lysis by CTLs, NK, or macros
chronic rejection
MONTHS OR YEARS after
unknown mech but fibrosis and collagen + accelerated atherosclerosis
-unresponsive to immunosuppression
alloreactivity
indirect
indirect alloantigen presentation = recipient APC + allogenic/foreign MHC to activate T cells
but CTLs not lyse foreign class I bearing bc can’t recognize non self class I MHC
alloreactivity
direct
donor/allogenic MHC + donor APC
polymorphic amino acids of foreign MHC mimick conformation of both self MHC and foreign peptide so TCR can recognize
alloreactivity activation
- direct donor dendritic cells and indirect recipient dendritic cells present alloantigens to stim CD4
- alloreactive CD4 T helper cells syn IL-2 and IFN-gamma for CD8 to syn CTLs to lyse graft cells
- alloreactive B cells prod antigraft antibodies
strategies to prevent rejection
- select most compatible graft to reduce graft immunogenicity
- immunosuppression
- deplete passenger leukocytes from graft, get rid of donor APC cells/dendritic cells
how to select most compatible
class I/II MHC proteins by serological and molecular techniques
-siblings may have some rejection from minor histocompatibility antigen diffs
immunosuppression strategy
- corticosteroids
- cyclosporine- best drug to inhibit cell mediated immunity but not as effective at inhibiting 2 immune resp compared to 1
- anti-lymphocyte globulin- common to get serum sickness (type III hypersensitivity)
graft vs host disease
- acute GVHD- quickly following marrow transplant, epi cells necrosis of skin/liver/GI
- chronic GVHD- fibrosis in organs
anti-CD3 antibodies + complement = dec incidence GVHD but dec chance of engraftment
graft vs leukemia effect
help prevent cancer bc GVHD rxn removes minimal residual disease/tumor cells but fine line
bone marrow donation
siblings best for HLA match
-relatively safe from pelvis
also do leukapheresis + sorting by flow cytometry for less invasive
fetal immunology
to prevent immune resp vs fetal antigens
-trophoblasts not xpr paternal MHC
-may secrete inhibitory cytokines
-tryptophan is broken down at fetal maternal interface so T lymphs react poorly to antigen
