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How does Graft-versus-host disease work?

Discussion in 'Step I' started by BlondeCookie, Jun 4, 2008.

  1. BlondeCookie

    BlondeCookie Senior Member
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    What I know about GVHD (Graft-versus-host Disease) is this...
    - bone marrow transplant to recipient
    - the donor's bone marrow contains mature T lymphocytes that attack cells of the recipient
    - thus the name, Graft-versus-host disease

    So, in order to have an immune response, the mature T-cells from the donor recognize the recipient cells as foreign, and an immune reaction ensues. My question is, if bone marrow is being transplanted, wouldn't there be immature T-cells transplanted from the donor instead of mature T-cells? If immature T-cells are transplanted, there would be no immune reaction and thus, no such thing as Graft-versus-host Disease. Obviously, this isn't the case.

    :confused:
     
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  3. Strength&Speed

    Strength&Speed Need more speed......
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    First of all, I'm curious why you are asking such a detailed question which won't likely be asked on Step 1. There will be enough mature T cells in bone marrow graft to attack the host. That's all you really need to know. I can't say for sure if the immature T's can mature in the host, but there will be enough mature T's to cause a problem.
     
  4. Pinkertinkle

    Pinkertinkle 2003 Member
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    Something about the thymus being where T cells mature and not bone marrow.
     
  5. MSKalltheway

    MSKalltheway I got the magic stick
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    I could have sworn I read somewhere that later in life after childhood, patients receiving a thymectomy were still able to produce mature T cells, so the thymus is not the only place mature T's come from...I dont think they are entirely sure where the mature T cells come from other than the thymus. Dont quote me on that though.
     
  6. BlondeCookie

    BlondeCookie Senior Member
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    From what I have learned in my Immuno studies, the bone marrow has stem cells, some of which develop into immature T-cells that travel to the thymus and become mature T-cells. Only mature T-cells have any functionality in the immune system. Thus, if we assume that bone marrow is transplanted to a recipient, then we also assume that immature T-cells are transplanted as well. So, how can we have Graft-versus-host Disease if those T-cells are immature and non-functional?

    Sorry for the minutiae in the post. I just want to figure this out for one of my practice questions. I'm sure my line of reasoning is flawed somewhere, but I just don't know quite where.

    :confused:
     
  7. synapse lapse

    synapse lapse tokyo robotic
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    I think we were taught along the lines of that mentioned above, that there are a number of mature T cells present in the graft BM that attack the host as "foreign" tissue, but Immuno was a long time ago and I don't feel like looking more into it right now.
     
  8. Strength&Speed

    Strength&Speed Need more speed......
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    I think the answer to your question is that there are mature as well as immature T-cells in the bone marrow. Its not 100% of one, 0% of the other.

    This is not the best source, but I'll copy an article:
    Hale, S Bright, G Chumbley, T Hoang, D Metcalf, AJ Munro and H Waldmann


    Graft-versus-host disease is one of the major problems in clinical bone marrow transplantation. Many experiments in animals have shown that it could be greatly reduced if mature T lymphocytes were removed from the donor marrow. Here we describe a new rat monoclonal antibody, CAMPATH 1, which is suitable for depleting lymphocytes from human marrow grafts. CAMPATH 1 is an IgM that fixes human complement. It binds to both T and B lymphocytes and some monocytes but not to other hemopoietic cells. When peripheral blood mononuclear cells were treated with CAMPATH 1 and complement, more than 99% of lymphocytes were killed and viable T cells could no longer be detected. Under these conditions, in vitro multipotential erythroid and myeloid colony-forming cells were unaffected. As well as being used for in vitro treatment of bone marrow to remove T cells, CAMPATH 1 could potentially be applied to other experimental and clinical situations where depletion of lymphoid cells is required, including serotherapy to achieve immunosuppression for organ transplants or to treat lymphocytic leukemias.
     
  9. medsurg2010

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    Not sure if you are looking for step 1 specific info, but I did have a Kaplan qbank question that incorrectly stated that gvhd was NK-cell mediated (I answered T cell, which was incorrect). I wrote kaplan an email marking this as an error in their qbank. +pissed+

    In fact, infusions of autologous NK cells with a BMT has been shown to decrease the incidence of GVHD and increase the preferable anti-tumor response. The questions you should be able to answer as far as step 1 is concerned (IMHO) are:

    1. MHC restriction and GVHD. Answer the question of: Why donor T cells become effector cells in an acute GVHD model if they are MHC-restricted?

    2. What are the minor and major antigens? Why is there still an allogeneic response in an identical twin bone marrow transplant-- minor antigens.

    3. What are the major cytokines involved in Th1 and Th2 reactions? What are the signals for activation of T cells?

    4. What are the 3 stages of acute gvhd and describe the cytokines in each.

    5. Know a clinical vignette of gvhd (symptoms and signs) and the time frame for hyperacute, acute, chronic rejection.

    Usually, grafts are T-cell depleted, but this may be a catch-22. Depleting T cells may not be entirely beneficial because the CD4+CD25+ foxp3+ T regulatory cells ("T regs") have been shown to prevent acute gvhd. FWIW, you should focus on the thymus serving as an organ to develop self-tolerance, not necessarily T cell maturation. In which case, it would make sense that tolerance would not be generated in an adult with an involuted thymus who receives a transplant of "immature T cells." Graft T cell maturation and expansion in the recipient is more dependent upon inflammatory cytokine production (thought to be caused by the chemo and/or radiation prior to the transplant). The activated T cells produce IL-2, which begins the "effector" phase, where clinical manifestations occur due to cytotoxic T cell damage to host tissue, thought to be initiated by graft T cell/ host antigen presenting cell interaction.

    This is a review that I found especially helpful (I was enslaved, er... I mean employed :beat: in a gvhd research lab in undergrad).

    Hope that helped. PM me with any questions.

    CITATION:
    Acute graft-versus-host disease: Pathophysiology, clinical manifestations, and management
    Daniel Couriel, M.D.*, Humberto Caldera, M.D., Richard Champlin, M.D., Krishna Komanduri, M.D.
    Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    email: Daniel Couriel ([email protected])

    *Correspondence to Daniel Couriel, Department of Blood and Marrow Transplantation, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 423, Houston, TX 77030-4009
     

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