Erin Rough Draft

Solid organ transplantation and bone marrow transplantation are commonly used as therapeutic options for many human diseases. There are many organ transplantations that have become standard therapy for many end-stage diseases. In the United States, about 25,000 patients a year undergo an organ transplant surgery (1). These include liver, kidney, heart, and lung transplants. The survival rate, along with the quality of life after a person receives an organ transplant has greatly improved due to new immunosuppressive therapy, surgical advances and medical management. About 1 and 5 year graft survival rates exceed 80% and 65% after most types of organ transplantations (1). Does this mean that 1 in 5, 1 to 5, or both 1 year and 5 year survival rate?Even with these improvements many complications still arise. On the top of this list is infection and allograft rejection. Both of these remain major causes of morbidity and mortality and are usually related to the immunosuppressive therapy organ transplant recipients receive.
Immunosuppression in transplant patients is a key aspect to graft survival. There are many immunosuppressive drugs being used today. Most of these depress cell-mediated immunity. if you keep this, describe briefly what cel-mediated immunity is Some examples of immunosuppressant agents include prednisone, which down modulates lymphocyte and macrophage function. Azathioprine inhibits cell proliferation interfering with DNA synthesis. Cyclosporine and tacrolimus blocks block T-cell activation and inhibits inhibit cytokine production (2). if cutting out that section, then i would reword the next sentenceThese immunosuppressive agents lead to an increase in susceptibility to intracellular pathogens that cause infection. Prevention of infection in organ transplant recipients is the optimal approach. However, this cannot always be achieved so Try replacing "so" with "making" early diagnosis and aggressive therapy is essential to graft and patient survival.
One of the major problems with organ/tissue transplantation is graft rejection. There are two types of graft rejection: acute and chronic. I know you describe typical symptons of chronic rejections later, but this might be a good spot for both Acute rejection occurs in approximately 30% of patients and presents usually "usually" would sound better in front of "presents" within the first 6 months as graft dysfunction (1). Chronic rejection is more common and usually presents sometimes years after surgery as a progressive decline in graft function (1). (a little confusing…Does it usually present years after surgery, or sometimes present years after surgery?) Graft rejection is thought to be a T-cell dependent response to human leukocyte antigen (HLA) incompatibility (1) although the exact nature of graft rejection remains a mystery to doctors. It is thought that T-cells respond to the foreign MHC molecules located in the graft from the donor the same way they react to any foreign protein (8). They secrete cytokines, divide, and differentiate, which leads to a large number of activated cells leading to graft destruction. There have been many attempts to try and analyze the exact role T-cells play in graft rejection. It has been shown that by blocking both CD40 and CD28 not quite sure what these pathways are, define then maybe? pathways, significantly inhibits allograft rejection in some mice. This strategy however was not able to prevent skin graft rejection due to inadequate blockade of CD8-mediated responses (3). This suggests that an effective strategy for some transplants would be to block the CD40 and CD28 pathways simultaneously. Also by pairing the blockade of CD40 and CD28 with anti-asialo GM1 antibodies, delays skin graft rejection since anti-asialo GM1 inhibits CD8-dependant dependent rejection (3). It has also been shown that CD4 T-cells play a crucial role in rejection. CD4 T-helper cells destroy the organs/tissues by helping B-cells form specific autoantibodies to what? and by inducing cell-mediated immune responses to target self antigens (4). When CD4 T-cells were depleted, the cardiac grafts in mice had long-term acceptance (5). What is considered "long term acceptance"? CD4 T-cells are necessary for mediating acute cardiac graft rejection. This response requires donor MHC class II expression (5). Also, this links direct donor recognition in this response. Therefore, CD4 mediated rejection depends on direct donor recognition of MHC class II and occurs without indirect presentation of donor antigens by host MHC class II molecules (5). One implication of this for a clinical setting would be to deplete, if possible, the donor MHC class II molecules from the organ being transplanted to reduce graft rejection. CD4 cells can function as effector cells in cardiac graft immunity when other lymphocyte subpopulations are absent (5).
One of the signs of chronic tissue graft rejection is parenchymal fibrosis associated with obliterating vasculopathy. It was observed different wording-Observations concluded that fibrosis and vasculopathy were not mediated by antibodies. This was demonstrated in chronic rejection in B-cell deficient mice (6). To put this one step further it is reasoned that Anti-donor T-cells could play a pathogenic role in this type of graft rejection. It was shown that the secretion of IL-4 by what was necessary for the obliterative graft vasculopathy associated with chronic rejection of MHC class II skin grafts (6). It was also noted that the fibrogenic effect of IL-4 is related to infiltration of eosinophils into the graft (6). The implications of these findings could mean that these cytokines could be potential targets for the prevention of graft rejection.
Coronary artery vasculopathy (CAV) is a complication that can arise in graft rejection what is CAV and why does it occur. The number of people who developed develop CAV after transplantation displayed display persistent alloreactivity after Try using "within" the first 6 months after transplantation Repetitive. Also both intramolecular and intermolecular spreading of epitopes was seen in patients with CAV in less than 2 years than patients that did not have CAV (7). This shows that there is a diversification of the immune response against the graft that leads to graft rejection. Also if a transplant patient could be monitored for epitope spreading after transplantation, the development of CAV could be prevented or caught at an early stage to where it can be treated to helpso treatment to avoid graft rejection is possible.
The easy solution to graft rejection is prevention or detecting detection of graft rejection early and noninvasive noninvasively? Im confused about the noninvasive part here.. Currently the method for detecting organ rejection is a biopsy, which is not only very invasive to a patient who is already trying to recover from surgery, but is also prone to sampling error (9). The use of an MRI, which is already a commonly used machine for other maladies, would provide a noninvasive and less stressful way to detect organ rejection after transplantation. It has been shown that macrophages play a crucial role in graft rejection. By monitoring macrophages with anvia MRI, doctors could diagnose graft rejection early. In order for the macrophages to be seen clearly on MRI, iron oxide particles can be injected into the cells in order to boost contrastboost contrast is a little awkward consider rewording on the MRI (9). If doctors were able to use this strategy the survival of organ transplant patients could be increased greatly. Any potential risks to patientsSo why isn't this method used if it is that good?
NEED Transition Toll-like receptors (TLRs) are transmembrane receptors that are an integral part of the immune system to detect microbial pathogens. MyD88 is a signal adaptor protein used by TLRs that leads to the release of inflammatory cytokines. This wording doesn't appear to lead to dendritic cells Dendritic cells are then allowed to mature and migrate to secondary lymphoid tissue, like the lymph nodes, and initiate an immune response by activating naïve T-cells. It is thought that TLR signaling may be activated in an organ transplant patient leading to an adaptive immune response (10). Goldstein et al showed in their research that in mice that had targeted disruption of the TLR signal adaptor MyD88 were unable to reject grafts with antigens that were mismatched. This was linked to the reduced number of mature and immature dendritic cells in the lymph nodes of grafts during the first two weeks after transplantation (10). These results have some very significant implications. If the MyD88 signaling pathway could be shut off after organ transplantation, organ rejection could decrease. Also this shows that the MyD88 pathway can be activated during solid-organ transplantation and not solely by infection. Graft rejection is a major concern for organ transplant patients and the sooner an effective way to prevent or detect graft rejection early is the key to organ transplantations to remain effective. Last sentence reads awkwardly
Another serious problem associated with graft function is ischemia/reperfusion injury if ischemia and reperfusion are interchangeable, state that at the beginning and then you don't need to put both terms for the rest of the paper. Ischemia/reperfusion (define or describe) injury has been found to be associated with retrieval, storage, and transplantation of organs from cadavers (1). It is thought that this affects early graft function and could possibly be a major factor limiting long-term graft survival (11). Ischemic insult has been shown in experimental models to increase MHC class II antigens (11). An increase in MHC class II antigens will increase the immune response against anything foreign, like the organ, in the patient. In a study the role of CD28-B7 co-stimulatory pathway was examined to see the part it playsto determine its role in renal ischemia/reperfusion. By blockingEarly blockage of the CD28-B7 pathway with the protein CTLA4Ig early as well as late organ dysfunction was almost completely prevented (11). This has an important impact in a clinical setting. The CD28-B7 pathway could be blocked in organ transplant patients preventing ischemia/reperfusion and increasing the survival of the graft.can you explain what the cd28 and B7 pathway is?
There are many complications that arise after organ transplantation because patients are placed on immunosuppressant drugs. There are many immunosuppressive drugs being used today, most of which depress cell-mediated immunity. Some examples of immunosuppressant agents include prednisone, which down modulates lymphocyte and macrophage function. Azathioprine inhibits cell proliferation interfering with DNA synthesis. Cyclosporine and tacrolimus blocks T-cell activation and inhibits cytokine production (2).didn't you already talk about examples of immunosupressive drugs and give the same examples earlier? Immunosuppression is necessary so the patient’s immune system does not attack the new graft. However, these immunosuppressive agents lead to an increase in susceptibility to intracellular pathogens that cause infection. Prevention of infection in organ transplant recipients is the optimal approach. However, this cannot always be achieved, so early diagnosis and aggressive therapy is essential to graft and patient survival. Immunosuppression in transplant patients is a key aspect to graft survival. Ok I'm confused, I thought we already went over this and it sounds like a conclusion, but then there is another paragraph
One of the more common virus infections in transplant patients is cytomegalovirus (CMV). About 20-60% of all transplant recipients have a symptomatic CMV infection (13). Although this virus is rarely fatal to those who get it, it still poses a significant threat on the transplant outcome. CMV disease is usually associated with high viral loads and can be effectively prevented using prophylactic antiviral medication (12). CMV is usually transmitted through the donor organ (2). The donor, whose immune system prevents CMV from replicating, may not have any symptoms of CMV. However, when the organ is placed into an immunocompromised patient, CMV is able to replicate. CMV has three major effects; it causes infectious disease syndromes, can cause increased immunosupression, and has been associated with graft rejection (2). The second of these effects is probably the most profound. Increased immunosupression leads to more opportunistic infections infecting the patient. The key the to maybe? CMV is detecting it early enough that these other pathogens cannot infect the patient. this sentence is worded awkwardly Hadaya, et al. have developed an ultra sensitive plasma PCR assay to detect CMV replication at an early stage. They showed that an ultra sensitive PCR assay could reproducibly quantify low levels of CMV DNA in plasma (12). This assay could be particularly helpful in determining when antiviral therapy should start and end during a CMV infection. By detecting CMV early, graft survival could be greatly increased.

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