The vertebrate immune system has evolved innate immune defense pattern recognition receptors (PRRs) that detect unmethylated cytosine-phosphate-guanine (CpG) motifs within bacterial DNA. Cellular activation by CpG motifs occurs via the Toll signal pathway. The Toll-like receptor-9 (TLR9, CD289) appears to be a major component of the CpG-DNA receptor, acting by direct binding to CpG- DNA, which triggers the induction of cell signaling pathways including the mitogen activated protein kinase (MAPKs) and NFkB, leading to stimulation of various cells of the immune system. The human TLR9 is expressed in B cells and plasmacytoid dendritic cells (PDC). Mice also express TLR9 in the myeloid compartment. Optimal sequences for activating TLR9 vary among species. Synthetic ODN contain CpG-DNA motifs mimicking the immunostimulatory effects of bacterial DNA and can, therefore, be used as immunoprotective agents, vaccine adjuvants and anti-allergic agents. CpG ODN also affects immune tolerance and autoimmunity. Different classes of CpG ODN are characterized each with distinct effects on the immune response: CpG-A ('D'-type), CpG-B ('K'-type), and CpG-C.