For the vast majority of the 54 years since the first kidney transplant, T cell–mediated
inflammation was believed to be the central process in allograft rejection. The therapies to prevent and
treat allograft rejection consequently have been directed primarily against T cells. The improvements in
these drugs have led to greatly improve rates of acute cellular rejection and 1-yr graft survival;
however, acute rejection does still occur, as does long-term chronic rejection. It was the development of
the immunohistochemical process for visualization of complement split product C4d in graft tissue that
provides concrete evidence linking antibody binding and complement activation in renal allografts to
the mechanism by which damage occurs in this setting. We now recognize that alloantibodies play a
role in rejections that do not respond to T cell therapies and, indeed, require targeted therapies that
address the various mechanisms by which they exert their effects. Newer, more sensitive technologies
for serum antibody screening are allowing for clearer delineation of the relationship between antibodies
and acute and/or chronic allograft pathologies and their attendant clinical outcomes. This chapter tries
to clarify the antigenic targets of the humoral alloimmune response, the mechanism of antibody
generation, the pathophysiology of antibody-mediated cell damage, the phenomenon of
accommodation, the mechanisms of allorecognition, the T cell-mediated rejection and overview of the
current understanding and classification of antibody-mediated syndromes. In addition two new aspects
of allograft rejection are discussed: the roles of chemokines and Toll-Like Receptors pathway
involvement in allograft rejections.
Keywords: Allografts, Antibodies, T cells, Chemokines, Antibody-Mediated Rejection, Acute Rejection,
Co-stimulation, Immunosuppression, Immunoodulation.
