Tolerance induction induced by monoclonal antibodies or co-receptor blockade is robust enough to resist breakdown by adoptive transfer of lymphocytes. Such resistance, the hallmark of dominant tolerance, is mediated by CD4 + regulatory T cells. CD4 + CD25 + T cells inhibit lymphopenia-m ...
Two-dimensional gel electrophoresis (2-DE) combined with protein identification by mass spectrometry (MS) is currently the method of choice in the majority of proteomic projects. Novel gel-free technologies have been developed but 2-DE remains the technique of choice for quantit ...
Because immune responses to transplant allografts are the main drivers of rejection, the ability to accurately quantitate antidonor immunity is an important goal in clinical transplantation. These allow for the prediction of presensitization to the transplanted tissue and the id ...
The real-time quantitative polymerase chain reaction (PCR), an increasingly popular technique for the detection of DNA, combines a high degree of accuracy with extreme sensitivity. In this chapter we describe the use of real-time quantitative PCR in trans-plantation research in two ar ...
The success of organ transplantation is critically dependent on the quality of the donor organ. Donor organ quality, in turn, is determined by a variety of factors including donor age and preexisting disease, the mechanism of brain death, donor management prior to organ procurement, the durat ...
Immunosuppressive strategies continue to evolve, with a number of new formulations having been developed in recent years. Although acute rejection rates may have diminished, current protocols of immunosuppression for chronic organ rejection are clearly inadequate. This comp ...
Graft arteriosclerosis (GA) is the leading cause of mortality in long-term survivors of solid organ transplantation. Although clinical studies have suggested a multifactorial etiology, the precise mechanism of disease remains obscure. Many animal models have been developed th ...
Renal transplantation is the best treatment for most patients with end-stage renal failure. It markedly improves quality of life and in some cases increases life expectancy. Advances in immunosuppression and other areas of practice have led to an incremental improvement in outcome; 1- and 5 ...
Clinical outcomes of pancreas transplantation were superior to that of islet transplantation until the introduction of the Edmonton protocol. Significant advances in islet isolation and purification technology, novel immunosuppression and tolerance strategies, and ef ...
Liver transplantation has become the treatment of choice for a wide range of end-stage liver disease. As outcomes have improved, so the demand for this therapy has increasingly exceeded the availability of donor organs. Access to liver transplantation is controlled such that donor organs a ...
Lung transplantation has come of age with the development of a critical mass of experienced clinicians who are committed to pooling their knowledge to solve the clinical problems that continue to confound the benefits individual patients may enjoy from these life-saving procedures. Ad ...
The dramatic improvements in 1-yr survival following cardiac transplantation have not been matched by similar improvements in long-term graft survival. Long-term survival of allografted hearts is limited by a progressive fibroproliferative disease, resulting in intimal th ...
The design and effectiveness of strategies to promote long-term graft acceptance requires a fundamental understanding of the mechanisms underlying acute and chronic rejection. This chapter discusses the two pathways of allorecognition-direct and indirect-and suggests th ...
Human leukocyte antigen (HLA) molecules are expressed on almost all nucleated cells, and they are the major molecules that initiate graft rejection. There are three classical loci at HLA class I: HLA-A, -B, and -Cw, and five loci at class II: HLA-DR, -DQ, -DP, -DM, and -DO. The system is highly polymorphic, the ...
Gene therapy holds great promise for treating a variety of human diseases and conditions. The field of gene therapy has advanced rapidly in the last decade. However, a major limiting factor remains the lack of a suitable vector for gene delivery. Although viruses are currently the most commonly re ...
A major complication associated with transplantation of solid organs is immunological rejection, which is currently controlled pharmacologically with immunosuppressive drugs, which must be administered indefinitely and may have harmful side effects. Gene transfer to do ...
It was recognized early last century that small molecules, known as haptens, can be made immunogenic after conjugation to carrier proteins (1). This principle has since been applied successfully to improve the immunogenicity of (poly)saccharides (2,3). We now know that the carrier protei ...
An adjuvant (immunopotentiator), when added to a vaccine, will enhance the immunogenicity of the antigen with the stimulation of an elevated humoral immune response. Some adjuvants may also stimulate a cell-mediated response against the antigen. One advantage of including an adjuvant ...
The success of candidate vaccines against infectious disease depends on their ability to activate components of the immune response (innate, cellular, and/or humoral) appropriate to the correlates of protection identified for the particular pathogen. Recombinant DNA technol ...
Despite obvious successes in controlling most serious childhood infections, there is a need to develop cheaper and more effective programs in infant vaccination. However, with the knowledge that adults are susceptible to diseases once believed to be only relevant to children, these cri ...