Possible mechanism of reciprocal enhancement between innate and adaptive immunity, through NF-kB and STAT-1/IRF-1 pathway. This sketch is built according to genes often described as upregulated during acute allograft rejection in human studies. NF-kB can be activated by a variety of inflammatory stimuli. For example, the engagement of toll-like receptors (TLRs) by the endogenous danger-associated molecules may lead to NF-kB activation and transcription of NF-kB induced genes, including TNF-α. TNF-α is a potent activator of NF-kB, thus forming an amplifying feed-forward loop. Indeed, NF-kB, through inducing transcription of CXCR3 and CCR5 ligands (e.g. CXCL9, -10 and CCL5 respectively), engages Th1 cells, CTLs and NK cells since all express CXCR3 and CCR5. These cells in turn produce IFN-γ with consequent activation of the STAT-1/IRF-1 pathway leading to further production of chemoattractants (CCR5 and CXCR3 ligands) with amplification of the IFN-γ response. IRF-1 can also induce TNF-α production, with further amplification of the loop.