Organ transplantation is an established treatment for patients with a wide variety of end-stage diseases. It is essential for physicians to familiarize themselves with the field of transplant medicine since an encounter with a transplant candidate or recipient is inevitable.¹

The immune system distinguishes self from nonself to eliminate potentially harmful molecules and cells. The immune system also has the capacity to recognize and destroy abnormal cells that derive from host tissues. Any molecule capable of being recognized by the immune system is considered an antigen (Ag). The skin, cornea, and mucosa of the respiratory, gastrointestinal (GI), and genitourinary (GU) tracts form a physical barrier that is the body’s first line of defense.²

Breaching of anatomic barriers can trigger 2 types of immune response: innate and acquired. Many molecular components (eg, complement factors, cytokines, acute phase proteins) participate in both innate and acquired immunity.²

Innate immunity

Innate (natural) immunity does not require prior exposure to an Ag (ie, immunologic memory) to be effective. Thus, it can respond immediately to an invader. It recognizes mainly Ag molecules that are broadly distributed rather than specific to 1 organism or cell. Components include phagocytic cells, natural killer (NK) cells, and polymorphonuclear leukocytes. Phagocytic cells (neutrophils in blood and tissues, monocytes in blood, macrophages in tissues) ingest and destroy invading Ags. Attack by phagocytic cells can be facilitated when an Ag is coated with an antibody (Ab), which is produced as part of acquired immunity, or when complement proteins opsonize Ags.

Natural killer cells kill virus-infected cells and some tumor cells. Polymorphonuclear leukocytes (neutrophils, eosinophils, basophils, mast cells) and mononuclear cells (monocytes, macrophages) release multiple inflammatory mediators.²

Acquired immunity

Acquired (adaptive) immunity requires prior exposure to an Ag and thus takes time to develop after the initial encounter with a new invader. This system remembers past exposures and is Ag specific. Components include cell-mediated immunity from T-cell responses and humoral immunity from B-cell responses (B cells secrete Ag-specific Ab).²

B cells and T cells work together to destroy foreign Ag. Ag-presenting cells (such as dendritic cells) are needed to present Ags to T cells.² The immune system is activated when circulating Abs or cell surface receptors recognize a foreign Ag. These receptors may be highly specific (Ab expressed on B cells or T-cell receptors) or broadly specific (such as pattern-recognition receptors called toll-like receptors). Immune activation occurs when Ab-Ag complexes or ­complement-coated molecules bind to surface receptors for the crystallizable fragment (Fc) region of immunoglobulin G (FcγR) and for C3b and iC3b.²

Once recognized, an Ag, Ag-Ab complex, or complement-molecule complex is phagocytosed. T cell–derived cytokines, particularly interferon-γ (IFN-γ), stimulate the phagocyte to produce more lytic enzymes and other bactericidal products and thus enhance its ability to kill or sequester the foreign Ag.² Unless Ag is rapidly phagocytosed and entirely degraded (an uncommon event), the acquired immune response is recruited. This response begins in the spleen for circulating Ag, regional lymph nodes for tissue Ag, and mucosa-associated lymphoid tissues (eg, tonsils, adenoids, Peyer patches) for mucosal Ag.²

The immune response in transplantation is a form of adaptive immunity. The principal targets are the major histocompatibility complex (MHC) molecules expressed on the surface of donor cells (allo-MHC). T-cell recognition of antigen is the primary event that initiates the immune response. This key step requires the interaction of the T-cell receptor (TCR) with antigen presented as a peptide by the antigen-presenting cell (APC) and a costimulatory receptor/ligand interaction on the T-cell/APC cell surface. Activated T cells are directly cytotoxic and provide help for B-cell antibody production and macrophage-induced delayed-type hypersensitivity (DTH) responses. Proteins encoded by the MHC are the principal antigenic determinants of graft rejection. Organs transplanted between MHC-identical individuals are readily accepted, whereas organs transplanted between MHC antigen-mismatched individuals are inevitably rejected in the absence of immunosuppressive agents.²

The antigen-presenting protein products of the MHC have been classified into class I and II groups that are characterized by structure, expression, and the cellular compartment from which they obtain antigenic peptides to present to T cells. Class I MHC molecules include human leukocyte antigen (HLA)-A, HLA-B, and HLA-C molecules and are found on all cell types except red blood cells. Class I molecules present cytoplasm-derived peptide antigens to CD8-positive T cells, which induce cell lysis.²

Class II MHC molecules include HLA-DP, HLA-DQ, and HLA-DR molecules. Class II MHC molecules are constitutively expressed on interstitial dendritic cells, macrophages, and B cells, but expression may be upregulated on epithelial cell and vascular endothelial cell after exposure to proinflammatory cytokines. Class II molecules present peptides derived from extracellular proteins to CD4-positive T cells.²

The activation of costimulatory pathways is required for T-cell entry into the cell cycle. Multiple costimulatory molecules have been identified including CD28 and CD40. Chemokine-regulated attraction of leukocytes to sites of tissue injury, infection, or allo-transplantation is essential for the induction of the acute inflammatory response.²

T helper cells are divided into 2 distinct populations, type 1 (Th1) and type 2 (Th2) cells. Type 1 T helper cells produce interleukin-2 (IL-2) and interferon-γ and induce macrophage activation, leading to DTH responses. Acute allograft rejection is predominantly mediated by a Th1 immune response. T-cell activation results in intracellular signaling that activates cytokine DNA promoter regions permitting transcription of mRNA.²

All allograft recipients are at risk of graft rejection; the recipient’s immune system recognizes the graft as foreign and seeks to destroy it. Recipients of grafts containing immune cells (particularly bone marrow, intestine, and liver) are at risk of graft-versus-host disease. Pretransplantation screening and immunosuppressive therapy minimize risk of these complications during and after transplantation.²

Transplantation uses allografts from living related, living unrelated, or deceased donors. Deceased donor organs can be recovered from heart-beating or so-called “brain dead” donors and from non–heart-beating or so-called “cardiac death” donors.¹

The United Network for Organ Sharing (UNOS) is a national, private, nonprofit organization that develops policies and guidelines, maintains data on wait lists, runs organ matches, and records all transplants. In the United States and Puerto Rico, 58 organ procurement organizations (OPOs) coordinate organ procurement in designated service areas.¹

Allocation of organs depends on disease severity for some organs (liver, heart) and on disease severity plus the time spent on waiting list for others (lung, kidney, and bowel).

Pretransplantation Screening

Due to the scarcity of donor organs, potential organ transplant recipients are thoroughly screened for medical and nonmedical factors to improve the likelihood of success given the risk and expense of transplantation.²

Tissue Compatibility

Both donors and recipients are universally tested for ABO antigens to ensure blood type compatibility and to prevent hyperacute rejection. Recipients are also tested for presensitization to donor antigens by checking panel reactive antibodies (PRA) against human leukocyte antigen. Human leukocyte antigen tissue typing is most important for hematopoietic stem cell and kidney transplantation. However, due to time constraints, HLA tissue typing is not typically performed prior to heart, lung, liver, and pancreas transplantation.²

Infection

To diminish the risk of donor-transmitted infections and reactivation of latent infections in recipients, several tests are performed pretransplant. These include serologic tests for cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), hepatitis B and C virus, and human immunodeficiency virus (HIV), and a tuberculin skin test (TST).²

Financial and Psychosocial

Given the expense and emotional burden of going through organ transplantation, candidates undergo consultations with financial coordinators and social workers for psychosocial screening.²

Indications and Contraindications

Indications and Contraindications are listed in Table 28-1.

In addition to organ-specific contraindications, there are general contraindications such as ABO incompatibility, active uncontrolled infection or sepsis, cancer (except for certain neuroendocrine, skin, and brain tumors or hepatocellular cancer confined to the liver), and the presence of advanced acquired immunodeficiency syndrome (AIDS) if human immunodeficiency virus positive. Relative contraindications include psychosocial morbidities such as substance addiction, known nonadherence with follow-up visits and medications, and active psychiatric problems. Extremes of body weight, poor functional status, and HIV status are considered contraindications on an individual basis.²