Ch. 19 Transplantation Flashcards
What’s an autograft?
Transplant from one area to another area of same individual
What is an isograft
Transplant from one to another that are genetically identical
What is an allograft?
Transplant between 2 of organisms of same species with DIFFERENT MHC self-antigens. Results in rejection, nonhistocompatible
What is a xenograft?
Graft between donor and recipient of different species. Histoincompatible
Which transplant is more flexible? Allograft or xenograft?
Allograft
What are other names for isograft?
Syngraft or symgraft
List the type of transplants from most to least durable
Autograft = isograft > allograft > xenograft
Which sugar is found in pigs but not humans?
GGTA (alpha 1,3 galactosyltransferase)
Which sugar is found in pigs but not humans?
GGTA (alpha 1,3 galactosyltransferase)
What happens during hyperacute rejection of transplanted pig organ cells in humans?
Human antibodies bind to GGTA sugar molecules on the surface of the pig cells
How did scientists bypass hyperacute rejection of pig organ transplants?
GGTA knockout pigs!
Describe first-set rejection of skin transplants
T cells activate. Skin appears normal for 2 weeks, then sloughs off several days later
Describe second-set rejection of skin transplants
Memory T cells activate. Skin is rejected within 6-8 days. Caveat: if skin from a different MHC mouse, the recipient immune system follows first-set rejection kinetics
Contrast first-set acute rejection at 5 days to second-set rejection at 7 days
Good vascularization and cell division in first-set VS no vascularization in second-set rejection
Describe the histological results of organ rejection
-lymphocyte and monocyte infiltration characteristic of DTH
-Both CD4 and CD8 T cells present
What is DTH?
delayed-type hypersensitivity (Type IV)
What condition manifests in humans without T cells? What causes this condition?
DiGeorge syndrome is caused by a hypoplastic thymus, meaning that T cell development failed
How do you slow down or prevent organ rejection?
Immunosuppressive drugs
Describe hyperacute rejection (time, antibodies, type of immunity)
-Occurs within minutes to hours
-Preformed Ab to incompatible MHC Ag from previous transplants, transfusions, or pregnancies, activate complement, platelet activation factor, and platelet activation
-Cell-mediated immunity NOT a factor
Describe why pregnancies are immunologically possible
The fetus is considered an “Ag” or “allograft” because can have incompatible MHC, so mom makes anti-MHC antibodies against dad’s MHC. HLA-G binds with KIR of NK cells, so they don’t kill fetal cells. Alpha-fetoprotein is an immunosuppresant that also helps fetal survival. Fetus expresses complement inhibitory protein. NO MHC II in placenta
Describe acute rejection (time, what type of recipient, mediated by which cells…etc)
-May begin a few days after getting kidney, with complete rejection within 10-14 days
-Occurs in recipient that has NOT been previously sensitized
-Mediated by T cell activation
-Occurs in people with mismatched tissue
-First-set rejection timeline
Consequences of acute kidney rejection?
-Enlargement and tenderness
-Reduced urine output
-Reduced renal blood flow
-Cell-mediated immunity with lymphocyte and macrophage infiltration
Describe chronic rejection (time, mediated by which immune system, kidney example…etc)
-Occurs over the span of months-years
-Environmental insult stimulated rejection
-Mediated by both Ab and cell-mediated immunity
-Proliferative inflammatory lesions of small arteries, interstitial fibrosis (scarred lungs)
-kidney example: slow renal failure
MHC stands for what? What was it’s old name?
Major histocompatibility complex. Used to be HLA (human leukocyte antigen)
Describe structural composition of MHC I
One alpha chain composed of A, B, or C. Also have beta chain (b2 microglobulin)
What is the role of the alpha chain in MHCI?
Ag presentation and immune response
What is the role of the beta chain in MHC I?
Location
What percentage of T cells are activated against MHC I after transplant?
5% (super high)
Which molecular component of MHC II must match between donor and recipient?
HLA D
Why are transfusions sometimes done before a transplant?
It introduces tolerance/desensitization
In allograft rejection, the immune response is mounted against which molecule?
MHC I
Name the types of MHC loci
Class I: HLA-A, B, and C
Class II: HLA -DP, DQ, and DR
Which MHC loci are cause for concern in potentially rejecting allograft?
HLA-A, B, or C
Describe the direct method of CD4 or CD8 T cell alloantigen recognition
APC from donor confuses host T cells into getting activated because they recognize the foreign MHC proteins
Describe the indirect method of CD4 or CD8 T cell alloantigen recognition
Recipient APC processes donor Ag and presents it to T cells. Often leads to Ab against donor tissue
Explain time details for blood transfusions to prep recipient for transplant
1-2 week intervals. 100-200 ml whole blood from donor
List the 3 drugs that block T cell proliferation and thus lead to immunosuppression
Cyclosporin A, FK506, and rapamycin
How do cyclosporin A and FK506 cause immunosuppression?
Block calcineurin phosphatase, which blocks IL-2 production. IL-2 normally activates T cells
How does rapamycin cause immunosuppression?
Blocks signal transduction after IL-2 binds IL-2 receptor
Which fetal cells do not express MHC I or II? Where are they found?
Trophoblasts. Found on outer layer of placenta. Do not prime mom’s immune system
Which protein do fetal trophoblasts express? Why do they not activate mother’s immune response?
MHCIb. They bind NK KIR, thus blocking NK cell activation. No fetal cell killing
Which proteins does the placenta not express?
MHC I with A, B, or C
List immunologically privileged sites. Why are they privileged?
-Fetus: explained earlier
-Corneal grafts: no HLA-D regions, blood and lymphatic circulation in cornea is minimal
-Brain: Most Ag in CSF generate B cell response, so more dangerous T cell response is avoided
-Testes: Sertoli cell barrier isolate sperm inside testes so host Ab can’t reach them
