Impact of Innate and Adaptive Immunity on Rejection and Tolerance

Abstract

Until recently, research on transplantation rejection and tolerance has been directed toward deciphering the mechanisms of the adaptive immune system. However, the emergence that the innate immune system, the body's first-line defense against pathogens, has a strong influence on adaptive immunity has galvanized interest in elucidating the interplay between these two arms of the immune system. The discovery of Toll-like receptors and the characterization of the cellular mediators involved in innate immunity have provided growing evidence that innate immunity affects the adaptive immune response. Emerging evidence has also shown that early "danger signals"' associated with ischemia-reperfusion injury or brain death contribute to innate immune activation, promoting rejection, and inhibiting tolerance induction. In addition, nonspecific stimuli such as increased donor age or patient disease may also serve to exert a synergistic influence on innate immune activation. Ultimately, controlling the events in innate immune activation may help drive tolerance induction and reduce the rate of rejection.

Treatment of Autoimmune Arthritis Using RNA Interference-Modulated Dendritic Cells

“…In physiological situations, DCs reside in an immature state, presenting Ags to T cells in absence of costimulation, therefore maintaining tolerance (1). In conditions associated with inflammation or tissue damage, DC maturation occurs, which is characterized by upregulation of costimulatory molecules and activation of T cells recognizing the Ag presented by DCs (2). This balance between tolerance and immunity has allowed researchers to use DCs for various types of immunotherapy.…”

The future of cardiac transplantation

“…The innate immune response is also suspected of mediating graft injury (27). Some have even theorized that ischemiareperfusion injury at the time of donor procurement alters gene expression, resulting in a rejection-susceptible protein milieu (28,29). The use of mTOR inhibitors, statins and vitamin C and E have been demonstrated to slow the progression of CAV, but to date, there is no therapy to completely prevent or reverse this significant complication.…”

Role of dendritic cells in cardiovascular diseases

“…DCs not only induce an immune response and participate in organ rejection, but also mediate transplant tolerance [84,94] . Hawiger et al [95] first reported that, in the absence of additional stimuli, DCs induce transient antigen-specific T cell activation followed by T cell deletion and unresponsiveness.…”

“…An evolving understanding of the multiple pathways involved in immune activation has resulted in many advances in immunology for transplantation medicine [84] . The adaptive immune responses medicated with T cell/B cell activation have been emphasized for the regulation of transplant rejection and the advance of immunosuppressive agents has improved long-term survival after transplantation.…”

“…DCs are potent antigen presenting cells involved in direct, indirect and semi-direct pathways of alloantigen recognition by the host immune system [84][85][86] . First, for the direct pathway, donor-derived DC and monocytes/macrophages that originally exist in the donor heart will leave the graft after transplantation and migrate to the recipient's secondary lymph system (including lymph node and spleen).…”