The immune response: the afferent arm

The key to understanding afferent immunity is the mechanism of activation of T lymphocytes by specialized antigen presenting cells, which bind antigenic peptide to Class II major histocompatibility molecules, and stimulate T cells via Signal 1 (antigen) and Signal 2 (costimulation). The best studied costimulatory pathway is the interaction of B7-1 or B7-2 ligand molecules on antigen presenting cells with CD28 or CTLA-4 receptors on T cells. T cell signaling occurs through the T cell receptor-CD3 complex and is augmented by cosignaling via CD4, CD8, and CD45. The activation of T cells to alloantigen occurs by either a direct pathway of recognition of allogenic major histocompatibility molecules (with or without an associated endogenous peptide), or by an indirect pathway of recognition of processed donor alloantigens via recipient antigen presenting cells. Afferent immunity on the musculoskeletal system is of special interest because of the absence of viable donor antigen presenting cells in processed grafts that makes them susceptible to the indirect pathway of alloantigen recognition.