Antibodies in transplantation

Abstract

Transplantation of cells, tissues, and organs from one individual to another can incite the production of antibodies specific for foreign antigens, especially major histocompatibility antigens, in the graft. Antibodies specific for a graft provide an index of immunity and a potential trigger for injury and rejection. However, the index of immunity can sometimes miss antibody-mediated rejection and besides causing injury the antibodies against a graft can also protect a graft from injury by blocking immune recognition, called enhancement, regulating activation of complement, and inducing changes in the graft that resist damage. Reviewed here are potential limitations in the use of antibodies as an index of immunity and the ways antibodies cause and/or prevent injury.

Figure 1

The distinct biological outcomes of organ, cell, and tissue grafts. Organ, tissue, and cell transplants all stimulate cellular and humoral immunity. The impact of immunity on these types of grafts differs greatly, however. To the largest extent, the impact depends on the way grafts receive a vascular supply. (A) Organ Transplants. Organ transplants have a foreign vascular tree. These grafts can be attacked by antibodies binding to foreign endothelial cells or by cellular immunity. Antibodies binding at the time of transplantation can cause hyperacute rejection, and antibodies produced after transplantation can cause acute vascular rejection (also called humoral rejection and antibody-mediated rejection) or chronic rejection. (B) Tissue and cell transplants. Tissue and cell transplants receive a vascular supply by in-growth of recipient blood vessels. The recipient blood vessels are not targeted by allo-reactive antibodies. Although small amounts of allo-reactive antibody and complement may diffuse beyond vascular spaces, these usually do not cause discernible damage. However, tissue and cell transplants are fully susceptible to cellular rejection. Sometimes humoral immunity prevents graft injury. Allo-reactive antibodies can induce enhancement which prevents cellular and possibly humoral rejection, and can induce accommodation which prevents humoral and possibly cellular rejection. Antibodies also control activation of complement.

Figure 2

Mechanisms of antibody-mediated protection. Besides causing injury to grafts, antibodies can protect grafts from injury. The mechanisms of antibody mediated protection include enhancement, complement control, and accommodation. In enhancement, antibodies bind to and block target antigens or interact with lymphocytes in ways that suppress lymphocyte functions. In complement control, antibodies serve as alternative targets for activation of complement (C3b and C4b), thus diverting complement away from cell surfaces. In accommodation, antibodies activate complement (C) on cell surfaces and in so doing change the biology of cells in ways that make the cells resist injury.