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Autoimmune Diseases

  1. Apr 23, 2004 #1
    Continuing with my classes' discussion of the immune system problems, we covered autoimmune diseases today. This posed a few more questions for me that I would like to ask the experts.

    1. In apoptosis, are components of the cell that is programmed to die recycled? Or are they excreted from the body?

    2. With tissue compatibility, there are two main classes of HLA (human leukocyte antigen) complexes. Class I is HLA-A, HLA-B, HLA-C. Class II is HLA-DR, HLA-DP, HLA-DQ. Do the letters after HLA represent anything? For the class I, my guess would be no. But for class II, I feel confused. I recognize that the R,P,Q that follow the HLA-D format are three letters that are located together in the alphabet, however my book listed them in the order above (DR, DP, DQ), which strikes me as slightly odd, because the alphabetical order of those three letters is PQR. Back-wards would be RQP. Is there any significance?

    3. We talked about grafting tissues. With autografts, we read that recent technology has made it possible to use a few cells of a burn patient's uninjured skin to culture extensive sheets of new skin. First, how is this done? How do they grow skin from only a few cells in culture? Where does normal skin come from? I know that normal skin is either keratinized or non-keratinized simple squamous epithelium. Does it originate from the basal membrane? And then perhaps a new skin cell develops beneath the current one and pushes the new ones off? What triggers the body to grow more skin? How reliable is this skin? Is it thick skin? Or just thick enough to cover the burn and then it grows down-wards to attach? Or how does it attach?

    4. We also talked about xenografts (organs or tissue transplanted from other animals to humans.) Is there much success/experimentation going on in this? I read about the heart valves from pigs, but beyond that I'm clueless.

    5. With radiation (I guess gamma), we learned how it stops rapidly dividing cells from dividing. Does it only stop rapidly dividing cells, or all cells? I see this is how they treat the cancer, because the cancer cells rapidly develop. But we learned the problem with high dosages of radiation (like Chernobyl in the Soviet) is that it kills the bone marrow, which produces WBCs and RBCs. Is this why radiation is so dangerous? Or does it cause other things also, like is it a mutagen as well? Is this the problem the people in Hiroshima had?

    Again, I thank any and everyone for reading this :-). I am really enjoying the immune system. I like this, and the parts about WBC, etc. But obviously they fit together, all the same stuff. I really enjoy it. Incidentally, I got accepted into my last-choice med-school yesterday, perhaps this is a field I can pursue in medicine.

    (Note: Moderators, masters, doctors: I realize that I am having a very one sided relationship with the forums--that of me pulling out a lot of information but not contributing much. I apologize for this, however I am just very inquisitive and like to learn all I can about the material I find interesting. You guys seem to be very knowledgeable, the experts, regarding this stuff. I hope this format I have taken of asking questions is OK with you guys.)
  2. jcsd
  3. Apr 23, 2004 #2


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    With regards to xenotransplantation, you mentioned porcine or pig valves. The use of pigs has primarily been driven by the advances in genetic engineering, which have resulted in the creation of pigs transgenic for human complement regulatory genes. (this, and the lack of protest of slaughtering pigs for such use vs. a closer primate such as chimps as well as the the lack of diseases that seem to be passed onto the human by pigs.)

    Prior to this event, pig organs transplanted into nonhuman primates (acting as surrogates for the human condition) would undergo a rapid and catastrophic rejection termed hyperacute rejection. This reaction was the result of antibody binding to pig endothelial antigens activating complement. The introduction of pigs transgenic for human complement regulatory proteins has resulted in improved graft survival in nonhuman primates.

    Ironically, because of the intense efforts to increase human donation for solid organ transplantation, the area in which the most clinical progress has been made in xenotransplantation will not help patients with end-stage failure of vital organs.

    Instead, those who will potentially benefit the most from xenotransplantation are the more than 9 million people in the United States alone with neurodegenerative diseases and stroke.

    The only xenografts that have achieved any real clinical success are cellular (versus solid organ) xenografts. After demonstrating success in allotransplantation of fetal neurons in patients with Parkinson's disease, researchers at an outfit called Diacrin have been able to successfully transplant fetal pig neuronal cells into the human brain for the treatment of Parkinson's disease and stroke, and into animal models for the treatment of Huntington's disease, focal epilepsy, and spinal cord repair.

    FDA approval is being sought for treatment of chronic intractable pain in humans by the transplantation of porcine neurons directly into the gray matter.

    Diacrin's lead cellular transplantation product, is in phase 2 clinical trials (double-blind, randomized, placebo, controlled). The investigators have shown that immature pig neurons differentiate and mature in the host brain. Phase 1 results showed a mean 20% improvement in patient function based on the Unified Parkinson's Disease Rating Scale after 12 months. A phase 3 study wasscheduled to begin mid-2000. I haven't kept up with it but will look it up.

    A Phase 1 clinical trial has also been initiated using fetal pig brain (LGE) cells to treat chronic striatal and cortical strokes. These cells will provide a substrate for re-establishing damaged pathways. The first patient, who was transplanted in September 1999 with "masking technology" (no immunosuppression regimen), has suffered a stroke of the middle cerebral artery 5 years before undergoing the transplant. This patient has shown improvement in the NIH stroke scale score, flexibility, spasticity, sensation to touch, and discrimination.

    Masking involves the treatment of the donor cells prior to transplantation to prevent T-cell activation. Alteration of initial T-cell recognition confers T-cell anergy and long-term acceptance of the graft. Fetal pig neurons are used preferentially over human neurons because fetal pig neurons are physiologically indistinguishable from human neurons and ethical issues associated with the use of human fetal tissue are avoided. HAR is not an issue because, lacking endothelium, neurons are dissociated cells.

    Anyway, that's just some info on xenografts.

    If I have more time I will try to help out with the others. Meantime, got to get back to work.
    Last edited: Apr 23, 2004
  4. Apr 23, 2004 #3


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    Most of the material is recycled but some is excreted.

    name for molecules in biology is sometimes meaningless. The letter probably represent when the protein was discover A is the first C was latter on. For PQR, R is probably the most recently id factor but migth be the most important factor that why it is listed first. Biologist have a crazy mind, sometimes name are an inside joke and have not logic. :wink:

    The cells are grown in special media in plates in a incubator then grafts on the patien. this is a standard procedure with standard growth medium. the layer grafted is not the outer most layer it is one of layer below. Your skin is mostly dead cells. The skin will grow back eventually without any signal, the grafted skin is just there to minimize bacterial infection and help to body recover faster.

    Radiation is a mutagen it will affect all cells and mutate all cells, higher radiation means higher DNA damage plus other damage as radiation level increase. But in therapy it is a precise aplication of the radiation. The cells stops dividing to correct mutation because the cell cycle stops. Another, idea behing radiation is to initatiate apoptosis in cancer cells.
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