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Chapter 63. Immunobiology of Heart and Heart-Lung Transplantation

Bartley P. Griffith

This chapter on the immunology of transplantation is a refreshed effort designed to promote a foundation for understanding the basic transplant immunologic fundamentals necessary for competency in caring for heart and lung transplant recipients. Although surgeons must acquire the technical expertise to perform these often demanding surgeries safely, the recipients' well-being additionally benefits from a surgical team well versed in basic transplant immunology. Comfort in treating patients who receive immunosuppressive therapies, both conventional and innovative, requires familiarity with the nonsurgical language of transplantation. The goal of this chapter is to squeeze the essentials1 into an understandable short text. The knowledge gained should permit surgeons to read immunology-tilted manuscripts with better understanding and thus make better decisions in treating their own patients. The core features of this alloresponse and new science are presented with some specific references to hearts and lungs so that the surgeon participating in the care of thoracic organ recipients can more easily build an understanding of the complex and evolving science. The material is organized to reflect a unifying theory of the immune response that determines the fate of an allograft and most often the heart or lung recipient as well. This includes: (1) histocompatibility; (2) activation of alloresponse T lymphocytes and T-cell–mediated rejection (TMR); (3) antibody-mediated rejection (AMR); (4) the underappreciated immune pathways, natural killer (NK) cells, and memory lymphocytes; and (5) immune plus gene monitoring. The text will clarify acute, cell-mediated, hyperacute, and chronic rejection pathways (Fig. 63-1).

Figure 63-1

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The alloresponse to a transplanted heart or lung may be grouped for simplicity into an early hyperacute rejection (HAR) based on preformed circulatory antibodies to blood group and in modern era HLA antigens (right panel) and acute cell-mediated rejection (AR) a more common and driving response that has been the focus of much of transplant immunology (left panel). AR is centered on the T lymphocytes becoming activated by specific HLA protein presented by antigen-processing cells. The CD4+ cells recruit inflammatory cells to the allograft and amplify other immune cells. The CD8+ T cells are directly involved with destruction of the allograft by cytotoxic intervention. Finally, chronic rejection (center panel) is the term given to describe progressive obliteration of the coronary arteries (chronic allograft vasculopathy, or CAV) in the heart or obstruction of small- and mid-sized airways (obliterative bronchiolitis, or OB) in the lung. These tubular structures are affected by injury and acute alloreactive hypersensitivity reaction.

Major histocompatibility complex (MHC) molecules are a family of proteins that vary quite a lot between individuals (genetic polymorphism) and represent the molecular basis for how immune systems distinguish self from nonself with respect to infections and transplants. MHC molecules on donor cells or MHC fragments, shed from thoracic organ transplants, are determined to be foreign by the immune regulatory system of the host. Intact MHC molecules expressed ...

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