Transplantation Immunology

IMMUNE RESPONSES TO ALLOGRAFTS, 366

Recognition of Alloantigens, 366 Activation of Alloreactive Lymphocytes, 371

PATTERNS AND MECHANISMS OF ALLOGRAFT REJECTION, 374

Hyperacute Rejection, 374 Acute Rejection, 374

Chronic Rejection and Graft Vasculopathy, 376

PREVENTION AND TREATMENT OF ALLOGRAFT REJECTION, 377

Immunosuppression to Prevent or to Treat Allograft Rejection, 377 Methods to Reduce the Immunogenicity of Allografts, 380 Methods to Induce Donor-Specific Tolerance, 382

XENOGENEIC TRANSPLANTATION, 382

BLOOD TRANSFUSION AND THE ABO AND Rh BLOOD GROUP ANTIGENS, 383

ABO Blood Group Antigens, 383 Other Blood Group Antigens, 385

HEMATOPOIETIC STEM CELL TRANSPLANTATION, 385

Graft-Versus-Host Disease, 386

Immunodeficiency After Bone Marrow Transplantation, 386

SUMMARY, 387

Transplantation is a widely used treatment for replacement of nonfunctioning organs and tissues with healthy organs or tissues. Technically, transplantation is the process of taking cells, tissues, or organs, called a graft, from one individual and placing them into a (usually) different individual. The individual who provides the graft is called the donor, and the individual who receives the graft is called either the recipient or the host. If the graft is placed into its normal anatomic location, the procedure is called orthotopic transplantation; if the graft is placed in a different site, the procedure is called heterotopic transplantation. Transfusion refers to the transfer of circulating blood cells or plasma from one individual to another. Clinical transplantation to treat human diseases has increased steadily during the past 45 years, and transplantation of kidneys, hearts, lungs, livers, pancre-ata, and bone marrow is widely used today (Fig. 16-1). More than 30,000 kidney, heart, lung, liver, and pancreas transplantations are currently performed in the United States each year. In addition, transplantation of many other organs or cells, including stem cells, is now being attempted.

Transplantation of cells or tissues from one individual to a genetically nonidentical individual invariably leads to rejection of the transplant due to an adaptive immune response. Rejection has been a major barrier to successful transplantation of tissues. This problem was first appreciated when attempts to replace damaged skin on burn patients with skin from unrelated donors proved to be uniformly unsuccessful. During a matter of 1 to 2 weeks, the transplanted skin would undergo necrosis and fall off. The failure of the grafts led Peter Medawar and many other investigators to study skin transplantation in animal models. These experiments established that the failure of skin grafting was caused by an inflammatory reaction called rejection. The conclusion that graft rejection is the result of an adaptive immune response came from experiments demonstrating that the process had characteristics of memory and specificity and was mediated by lymphocytes (Fig. 16-2). For instance, rejection occurs in 7 to 14 days after the first transplant from a donor to a recipient (called first-set rejection) and more rapidly after the second transplant from the same donor to this recipient (called second-set rejection), implying that the recipient developed memory for the grafted tissue. Individuals who have rejected a graft from one donor show accelerated rejection of another graft from the same donor but not from a different donor, demonstrating that the rejection process is immunologically specific. These

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