Flashcards in Lecture 18: Fetal Transplant Deck (59)
What unknown fact have microarrays elucidated about predicting severe rejection?
if B cells are present
What is chronic rejection?
repeated, slow attrition of graft
Are chronic rejections caused by the same mechanisms acute rejections are?
NO; chronic via unknown mechanism
What is the pathology of chronic rejection?
intimal thickening that leads to graft ischemia
What is the ultimate goal to prevent graft rejection?
Name 4 strategies to prevent rejection:
1) optimally match MHC (especially DR)
2) block t-cell response to alloantigens
3) provide inhibitory second signals (CTLA-4), Tregs (CD4, 25) or cytokines (IL21, 23, 10, TGFb to override Th1, 17 and CD8)
4) INDUCE TOLERANCE BY MANIPULATING TREGS
Graft vs. Host disease (GvH) is unique to what?
bone marrow transplantation (or inadvertent transfusion of immunocompetent cells into an immunodeficient host)
What needs to happen before bone marrow transfusion occurs?
host needs to be essentially immunologically bankrupt (need to wipe out host's T cells)
How do you set up an assay to test for compatibility of bone marrow?
recipient cells are the stimulators and donor cells the responders ----- effectively the opposite of how you would set it up for a solid organ transplant
Why don't xenotransplants work?
a 1,3 GT gene which higher primates develop antibodies against
What can help blunt the autoreactivity to xenotransplants?
insert Human Decay Activating Factor (DAF) to activate complement and break it down so it wont cause inflammation
What is the rate of first trimester failure?
True or false: trophoblast (fetal tissue) does not express HLA-A B or C
True (it is downregulated)
What kind HLA is expressed on trophoblast tissue?
non classical HLA-G that expresses an inhibitory motif for maternal NK cells
What is special about the HLA-G?
it expresses inhibitory motif for maternal NK cells
What prevents the expression of cytokines that would promote cytotoxic T cells?
In the non-pregnant uterus, NK cells ___________ (increase or decrease)
In the gravid uterus, what happens to NK cells?
convert to markedly different NKs and make up 70% of all lymphocytes
What is special about the NKs in the pregnant uterus?
they do NOT express CD16 (the Fc receptor necessary for antibody-directed cytotoxicity)
they have regulatory and tolerogenic functions that prevent immune cytotoxic attack
also help with angiogenesis
what other immune cells are upregulated in the pregnant mom?
yd T cells, macs, paterna antigen specific CD4, 25 Tregs
these secrete IL10 and TGFb to tone down immune response
What two cytokines strongly promote the presence of Tregs?
IL-10 and TGFb
What does progesterone do in terms of maternal pregnancy?
suppresses Th1 type response
The pregnant mom has suppressed _____ response but normal ____ response
True or false: during pregnancy, mom has increased numbers of paternal MHC antigen specific maternal Tregs circulating
What else does progesterone do to the surface of the uterine endometrium to subdue immune response?
displays decay accelerating factor (DAF) to inhibit complement mediated death
What is the best characterization of the mom's immune system state during pregnancy?
dominant Th2 but suppressed Th1, Th17, and cytotoxic responses
What happens if the dominant Th2 converts to Th1 bias with dominance of IFNy at the fetal/maternal interface?
inability for successful implantation or fetal resorption
Why can the Th2 bias be harmful?
leads to exacerbation of maternal diseases dependent on TMMI (like Tb)