Lecture 18: Fetal Transplant Flashcards Preview

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Flashcards in Lecture 18: Fetal Transplant Deck (59)
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31

What unknown fact have microarrays elucidated about predicting severe rejection?

if B cells are present

32

What is chronic rejection?

repeated, slow attrition of graft

33

Are chronic rejections caused by the same mechanisms acute rejections are?

NO; chronic via unknown mechanism

34

What is the pathology of chronic rejection?

intimal thickening that leads to graft ischemia

35

What is the ultimate goal to prevent graft rejection?

stimulate tolerance

36

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

37

Graft vs. Host disease (GvH) is unique to what?

bone marrow transplantation (or inadvertent transfusion of immunocompetent cells into an immunodeficient host)

38

What needs to happen before bone marrow transfusion occurs?

host needs to be essentially immunologically bankrupt (need to wipe out host's T cells)

39

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

40

Why don't xenotransplants work?

a 1,3 GT gene which higher primates develop antibodies against

41

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

42

What is the rate of first trimester failure?

30%

43

True or false: trophoblast (fetal tissue) does not express HLA-A B or C

True (it is downregulated)

44

What kind HLA is expressed on trophoblast tissue?

non classical HLA-G that expresses an inhibitory motif for maternal NK cells

45

What is special about the HLA-G?

it expresses inhibitory motif for maternal NK cells

46

What prevents the expression of cytokines that would promote cytotoxic T cells?

epigenetically silencing

47

In the non-pregnant uterus, NK cells ___________ (increase or decrease)

increase

48

In the gravid uterus, what happens to NK cells?

convert to markedly different NKs and make up 70% of all lymphocytes

49

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

50

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

51

What two cytokines strongly promote the presence of Tregs?

IL-10 and TGFb

52

What does progesterone do in terms of maternal pregnancy?

suppresses Th1 type response

53

The pregnant mom has suppressed _____ response but normal ____ response

Th1

normal Th2

54

True or false: during pregnancy, mom has increased numbers of paternal MHC antigen specific maternal Tregs circulating

TRUE

55

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

56

What is the best characterization of the mom's immune system state during pregnancy?

dominant Th2 but suppressed Th1, Th17, and cytotoxic responses

57

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

58

Why can the Th2 bias be harmful?

leads to exacerbation of maternal diseases dependent on TMMI (like Tb)

59

What happens if fetus is infected in utero?

can develop tolerance to that and not handle it well the next time it sees that pathogen