GVH and Digeorge Syndrome?

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mountainman123


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Hello, I am reading RR Pathology and I am confused on this and was hoping that someone can clear it up. It says that Graft vs. Host disease is basically a problem of the donor T-cells recognizing the host tissue as foreign and it activates the hosts CD4 and 8 T-cells. So why is there a danger of GVH in a child with Digeorge syndrome who lacks a thymus and thus no T-cells. I ask becuase on pg. 54 of RR it says that there is a danger of GVH reaction. Thanks in advance.
 
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mountainman123

Yeah, it is the donor T-cells that are recognizing the host tissue as foreign and that leads to activation of the hosts/recipients T-cells. At least that is what it says in RR path on page 47 under pathogenesis. That is why it doesn't make sense because in Digeorge there are no T-cells to activate.
 

pleaseletmepass

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this doesn't answer your question, but children with DiGeorge Syndrome eventually do develop functional T-cells, despite the lack of a thymus. sorry i cannot provide any further detail on why this is so...:oops:

-plmp
 

fakin' the funk

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GVHD is a problem of HOST T-cell immunodeficiency due to immunosuppression.

DONOR T-cells are allowed to proliferate and destroy "foreign" cells because the weakened, depleted host T-cells cannot destroy them. Remember, GVHD is particularly a problem in bone marrow transplantation where the host marrow has been eradicated by irradiation.

A patient with DiGeorge syndrome is essentially always in the bone-marrow-transplant-recipient state of being effectively T-cell-less.
 

ShawnW59

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First, a GVHD can only occur if:
1) an immunocompetent graft is transplanted
(bone marrow, spleen, liver, etc.; although most BMT are irradiated to prevent the likelihood of GVHD promoted by mature T-cells in the graft)

2) the host/recipient is histo-incompatible or simply put: the graft recognizes the host as 'foreign'

3) the host/recipient is immunocompromised; this is important because the host/recipient will not be able to fight off the graft (host vs. graft instead) and in return allow a graft-vs-host disease to occur

Before answering to the question at hand...
- Kaplan did not make a mistake IMO, they did correctly say the host deficient of CD4⁺ Th-cells are free of GVHD
- Although the people who said 'donor' with immunocompromised diseases, who are deficient of CD4⁺, will result in the lack of GVHD against the recipient are correct; however, I don't believe a BMT of such individuals are proven 'fit' for transplant; purpose of BMT is to supply an immunocompromised patient with immunocompetency (if that's a word) and not supply the patient with a graft of equal immunocompromised state

Now, for the question at hand...please correct me if I'm wrong!
- To lack CD4⁺ cells in the body can most likely mean a lack of MHC-II receptor, and most likely in the thymus where the maturation of Th-cells happens
- Without MHC-II receptors the vigorous self-tolerance maturation steps for Th-cells/CD4⁺ can never occur
- It is the diseases such as SCID, DiGeorge syndrome, BLS (MHC-II deficiency), AIDS (CD4⁺ compromised) and others that can cause the host to be deficient of MHC-II and CD4⁺

- Acute GVHD is more CD4⁺/MHC-II mismatch-mediated; it makes sense because the Th-cells are the major component that also mediate the effector phase of host-vs-graft rejection; the 2° activation of macrophages, increased ability of CTLs, complement system, antibody class switching, etc. are all mediated through Th-cell activation to promote such a powerful 'attack' against the immunocompromised host; however the MHC-II needs to be present in the host for the donor Th-cells to be activated; hence the question at hand can be answered as to why CD4⁺/MHC-II deficient recipients are more likely to be free of GVHD response in BMT's.

- Chronic GVHD is more CD8⁺/MHC-I mismatch-mediated; this also makes sense because even in CD4⁺ deficient individuals GVHD can also occur, although not as fast and most likely through the remainder pathway of MHC-I/CTLs; without Th-cells the CTLs lack the ability to upgrade to a better killing machine and may take longer to fight against the host

- We also must keep in mind the time-frame of GVHD; to mount an attack against the host will not only need the mature left-over T-cells of immunocompetent grafts but along that a memory formation by those cells and then proliferation of immune cells that recognize the host as 'foreign' and increase in number large enough to 'win the war against the host' (haha)

I hope I am somewhat along the lines of the correct response, if I am false in any way please let me know! I am also a student and constantly trying to learn new things =)
 
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