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Key Concepts

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  • The major histocompatibility complex (MHC) consists of a genomic region that encodes a large and diverse group of proteins that are expressed on all cells. The two major classes of MHC molecules include class I molecules that are found on all nucleated cells and present antigen to CD8 positive (CD8+) “cytotoxic” T cells and natural killer (NK) cells. Class II MHC molecules occur on antigen presenting cells and present antigen to CD4 positive (CD4+) “helper” T cells.

  • Normal development of immunotolerance occurs primarily in the thymus whereby T cells displaying different T-cell receptor complexes interact with thymic epithelial cells.

  • Antigen presenting cells (APCs) are the most potent initiators of alloimmune responses because they express high levels of both MHC class I and class II antigens. APCs also express costimulatory molecules that provide secondary signals necessary for expansion of the T-cell response to alloantigens.

  • T-cell receptor activation by MHC activates calcineurin. Calcineurin, in turn, activates a transcription factor that increases the interleukin-2 (IL-2) production and other cytokines.

  • Secreted IL-2 binds to immune cell surface IL-2 receptors (IL-2R) and stimulates expansion of the local immune cell population (predominately T cells), resulting in increased inflammatory cells in the donor organ and injury manifested as epithelial cell or myocyte death.

  • B cells mediate the antibody response to alloantigen, specifically donor endothelial cells. Antibody binding to alloantigen activates a complement cascade that causes endothelial injury resulting in interstitial hemorrhage, microthrombosis, and an influx of inflammatory cells.

  • Hyperacute rejection occurs within the first 24 h after transplantation and is generally dependent on the presence of preexisting anti-human leukocyte antigen (anti-HLA) antibodies that coat the endothelium and activate complement.

  • One known mechanistic pathway of bronchiolitis obliterans syndrome, or chronic lung allograft rejection, is the sensitization of CD4+ T cells to MHC class I and class II molecules. Much of the resultant lung injury is from indirect pathway activation.

  • Chronic allograft vasculopathy observed in cardiac allografts is thought to result from injury to the coronary artery endothelium. Sources of injury include immunologic (e.g., innate, T-cell–mediated, antibody-mediated) and nonimmunologic (e.g., diabetes, obesity, hyperlipidemia, hyperhomocysteinemia, and CMV) factors.

  • During the first year after transplantation, acute rejection is noted in about 25 percent of heart transplant recipients and 36 percent of lung transplant recipients.

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Overview of Chapter

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The authors would like to acknowledge Norman Barker and Dr. Peter Illei for their help with the images in this chapter.

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After the technical challenge of lung or heart transplantation has been successfully achieved, the process of maintaining a healthy graft begins. For this, a general understanding of the immunobiology of thoracic transplantation is needed. This chapter will provide a background on the immune system and allorecognition. It will describe how the immune system mediates rejection of lung and heart transplants, types of organ rejection, and the histologic appearance of rejection. It will further describe methods to monitor allograft rejection ...

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