Tolerancia En El Trasplante Renal

Chapter 21

Tolerance in Renal Transplantation
Marco Antonio Ayala-García, Beatriz González Yebra, Éctor Jaime Ramirez Barba and Eduardo Guaní Guerra
Additional information is available at the end of the chapter http://dx.doi.org/10.5772/54734

1. Introduction
Tolerance in human transplantation can be defined in two ways [1]. Clinical tolerance (also referred to as clinical operationaltolerance [2]) is the survival of a foreign organ or tissue (allogeneic or xenogeneic) in a normal recipient in the absence of immunosuppression [1]. Immune tolerance is the absence of a detectable immune response against a functional organ or tissue in the absence of immunosuppression [1]. Early evidence demonstrating that adult mice could be tolerant of skin grafts after the induction of neonataltolerance by the introduction of splenocytes intraperitoneally was shown by Brent and Medawar, in 1953 [3]. The central role of the thymus in mediating cellular immunity and graft rejection was established by JFAP Miller, who showed that nude mice tolerated skin allografts because of a marked deficiency of lymphocytes [4]. Conversely, there have been recent studies that show that spleentransplantation in pigs or dogs has a tolerogenic effect on renal transplantation [5, 6]. On the basis of the promising results obtained in these animal models, several tolerogenic protocols have been attempted in humans, but most have failed to achieve robust and stable tolerance after renal transplantation. This is due to that the transplantation immunobiology is very complex, because of the involvement ofseveral components such as antibodies, antigen presenting cells, helper and cytotoxic T cell subsets, immune cell, surface molecules, signaling mechanisms and cytokines; which play a role in the alloimmune response.

2. The alloimmune response
The allogeneic immune response has largely been attributed to the recognition of donor antigens, presented in the context of human leukocyte antigen(HLA) molecules to T cells,

© 2013 Ayala-García et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

464

Current Issues and Future Direction inKidney Transplantation

which in turn direct a huge array of cellular and humoral responses, causing tissular damage and graft rejection. This type of response is mediated by the adaptative branch of the immune system [7]. The immune system can be divided in two components, the innate and adaptative immunity. The innate immunity, refers to a nonspecific response that involves the recruitment ofdiverse components of the immune system such as, macrophages, neutrophils, natural killer cells (NK cells), cytokines, several cellular receptors, complement components, cytokines, Toll-like receptors (TLRs), and antimicrobial peptides (AMP’s). The adaptative immunity, which involves recognition of specific antigen, conferring both specificity and a memory effect [8]. Data suggest that initialallograft injury (such as ischemia) may initiate an innate immune response (Figure 1A), thus contributing to acute and chronic allograft rejection. Furthermore, this inflammatory response may initiate and expand the adaptive immune response to the point where the different HLA antigens come into play for the first time [9]. Some immunol‐ ogist choose not to divide the alloimmune response in adaptativeand innate branches; nevertheless, they are closely related and dependent on each other. The main and strongest responses to alloantigens are mediated by host T cells, which recognize peptide antigens presented by antigen presenting cells (APCs) in the context of HLA. The phenomenon by which the recipient immune system reacts with donor antigens that are considered to be “non-self” is called...