Question

Develop a 1- to 2-page case study analysis in which you: Based on the scenario.

• Explain why you think the patient presented the symptoms described.
• Identify the genes that may be associated with the development of the disease.
• Explain the process of immunosuppression and the effect it has on body systems.

Scenario 3: A 34-year-old Hispanic-American male with end-stage renal disease received a kidney transplant from a cadaver donor, as no one in his family was a good match. His post-operative course was uneventful, and he was discharged with the antirejection drugs Tacrolimus (Prograf), Cyclosporine (Neoral), and Imuran (Azathioprine). He did well for 3 months and had returned to his job as a policeman. Six months after his transplant, he began to gain weight, had decreased urine output, was very fatigued, and began to run temperatures up to 101˚F. He was evaluated by his nephrologist, who diagnosed acute kidney transplant rejection.

Answer 1

The symptoms are due to acute graft rejection. Weight gain is due fluid retention, decreased urine output is due to diminishing renal function and fever can be due to infection as a result of immuno suppression.

The degree of immune response to a graft depends partly on the degree of genetic disparity between the grafted organ and the host. Xenografts, which are grafts between members of different species, have the most disparity and elicit the maximal immune response, undergoing rapid rejection. Autografts, which are grafts from one part of the body to another (eg, skin grafts), are not foreign tissue and, therefore, do not elicit rejection. Isografts, which are grafts between genetically identical individuals (eg, monozygotic twins), also undergo no rejection.Allografts are grafts between members of the same species that differ genetically. This is the most common form of transplantation. The degree to which allografts undergo rejection depends partly on the degree of similarity or histocompatibility between the donor and the recipient

The antigens responsible for rejection of genetically disparate tissues are called histocompatibility antigens; they are products of histocompatibility genes. Histocompatibility antigens are encoded on more than 40 loci, but the loci responsible for the most vigorous allograft rejection reactions are located on the major histocompatibility complex (MHC).In humans, the MHC is called the human leukocyte antigen (HLA) system and is located on the short arm of chromosome 6, near the complement genes. Other antigens cause only weaker reactions, but combinations of several minor antigens can elicit strong rejection responses. The MHC genes are codominantly expressed, which means that each individual expresses these genes from both the alleles on the cell surface. Furthermore, they are inherited as haplotypes or 2 half sets (one from each parent). This makes a person half identical to each of his or her parents with respect to the MHC complex. This also leads to a 25% chance that an individual might have a sibling who is HLA identical.

Mechanism of rejection.

The immune response to a transplanted organ consists of both cellular (lymphocyte mediated) and humoral (antibody mediated) mechanisms. Although other cell types are also involved, the T cells are central in the rejection of grafts. The rejection reaction consists of the sensitization stage and the effector stage.

Acute rejection manifests commonly in the first 6 months after transplantation.

Acute cellular rejection

Acute cellular rejection is mediated by lymphocytes that have been activated against donor antigens, primarily in the lymphoid tissues of the recipient. The donor dendritic cells (also called passenger leukocytes) enter the circulation and function as antigen-presenting cells (APCs).

Humoral rejection.

Humoral rejection is form of allograft injury and subsequent dysfunction, primarily mediated by antibody and complement. It can occur immediately posttransplantation (hyperacute) or during the first week. The antibodies are either preformed antibodies or represent antidonor antibodies that develop after transplantation. Proteinuria is associated with donor-specific antibody detection and is likely to be an important factor that determines rapid glomerular filtration rate decline and earlier graft failure in patients developing de novo HLA antibodies.