Activation of NF- κ B signaling through canonical and alternative pathways. Different cytokines and pathogen associated molecules (PAMs) interact with their specific receptors (cytokine receptors:TNF receptor, IL1 receptor; PAMs recognize TLRs present on outer cell membrane (TLR1,-2,-4,-5,-6, and -10) or on the endosomal membrane (TLR3, -7, -8 and -9) in the initial stage of NF- κ B activation pathway. The activated receptor recruit the adapter components (not shown) such as Myd88 and TRIF (TIR domain-containing adaptor inducing IFN- γ, except TLR3 which utilizes TRIF without Myd88 (Myeloid differentiation primary response protein 88) to transmit the signal through activation of several mediators components including IRAK4 (IL1 receptor associated kinase 4), TRAF6 (TNF receptor associated factor 6), to activate IKKK i.e., MEKK1 (mitogen activated protein (MAP) kinase/extracellular signa l regulated kinase (ERK) kinase kinase 1), MEKK3 and TAK1 (transforming growth factor β activated kinase) to act to phosphorylate IKK complex. The activated IKK modifies the inhibitor I κ B for its proteasomal degradation. NF- κ B is released free to enter into the nucleus for transcriptional activation of the target genes. The canonical pathway is active in innate immunity, inflammation and cell survival; the alternative pathway mediates the humoral immunity.