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24 Cards in this Set

  • Front
  • Back
mc etiologies of renal dz leading to kidney transplantation
diabetes
chronic gn
pkd
autologus
graft from self
synegenic graft
grafting from identical twin or clone
allograft
from nonidentical individual of same species
xenograft
from different species
MHC molecules
also called human leukocyte antigens (HLA); encoded in MHC locus on chromosome 6 in humans

function to present peptides to T cells
MHC I vs II expression
I: on APCs (DC, macrophage, B cell) (binds CD4+ helper)
II: on all nucleated cells (and platelets) [leukocytes, epithelial cells, mesenchymal cells) = bind w CD8+ CTL for killing
MHC expression and inheritance
polymorphic (many diff alleles are present in the population)
an entire HLA locus is inherited from each parent
alll inherited alleles are expressed (called codominant expression)
which chromsome are MHC I/II encoded on
human chromosome 6

you inherit one haplotype from each parent
if an identical donor is not available (sibling = 1:4 chanc eo fbeing identical) w identical HLA haplotype whats the next best option?
choose donor w compatible blood type and closest match at HLA-DR (bc Dr is highly polymorphic and highly expressed)
why are HLA- A and B more important than C
bc A/B are very polymorphic while C is not
why is HLA matching done more for kidneys than for liver, heart or lung
anatomical compatibility, need to minimize organ storage time etc. may override the benefits of HLA matching (for unknown reasons rejection against liver transplants is weaker than might be expected)
the role of MHC (HLA) in rejection
Either recipient’s T cells cross react with allogeneic MHC/peptide complex (direct recognition)
Or recipient’s DCs process allogeneic MHC molecules into peptides, and present these peptides on self MHC (indirect recognition)
direct recognition
recipient’s T cells cross react with allogeneic MHC/peptide complex (graft presents the antigen)

Direct = Donor APC (D=DAPC)
indirect recognition
recipient’s DCs process allogeneic MHC molecules into peptides, and present these peptides on self MHC
Hyperacute rejection
Antibodie mediated (type II) due to preformed antidonor antibodies in the transplant recipient. Occurs within minutes after transplantation
Acute rejection
Cell mediated due to cyotoxic T lymphocytes reacting against foreign MHCs. Occurs weeks after transplantation. Reversible w immunosuppressants such as cyclosporine and OKT3.
Chronic rejection
T-cell and antibody mediated vascular damage (obliterative vascular fibrosis); occurs months to years after transplantation. Irreversible. Class I-MHC (non self) is perceived by CTLs as class I-MHC (self) presenting a non self antigen

Infiltrates of plasma cells and eosinophils, concentric endothelial proliferation, fibrosis of graft
Mycophenolate mofetil
Inhibits de novo guanine synthesis and blocks lymphocyte production
Tx of acute rejection
Anti-CD3 monoclonal ab opsonizes and causes complement mediated lysis of T cells (used to tx acute rejection)
Cyclosporine
MOA: Blocks differentiation and activation of T cells by inhibitng calcineurin, thus preventing the production of IL-2 and its receptor.

Clinical use: Suppresses organ rejection after transplantation; selected autoimmune disorders

Toxicity: Predisposes pts to viral infections and lymphoma; nephrotoxic (preventable w mannitol diuresis)
Treatments for graft rejection
drawbacks of immunosuppresion
Increased incidence of infections

Increased incidence of tumors especially those produced by oncogenic viruses

Cyclosporine is nephrotoxic
Graft vs Host disease
Immunologically competent donor cells placed into a immunodeficient recipient; memory T cells (CD4+Th1s, CD8+ CTLs) transplanted into an irradiated recipient

Immunocompetent T cells (Graft) recognize the recipients HLA antigens as foreign and react against (vs) the recipient (host)

thus HLA matching VERY important in bone marrow transplantation (injected BM hones to irridated/removed BM)

Major organs affected = skin (rash), liver (jaundice) and intestines (bloody diarrhea).