CpG oligodeoxynucleotides, also known as CpG ODNs, are short segments of synthetic DNA containing an unmethylated cytosine-phosphate-guanine (CpG) dinucleotide motif. In vertebrates, methylation of CpG dinucleotides is common except in certain genomic regions like CpG islands. The immune system recognizes unmethylated CpG motifs as a signature of bacterial and viral DNA, secreting cytokines to trigger an innate immune response. Scientists have studied the use of synthetic CpG ODN to modulate the immune system in a controlled manner.

Mechanism of Immune Activation
When CpG Oligodeoxynucleotide is introduced into cells, it is recognized by the Toll-like receptor 9 (TLR9) located inside endosomes and lysosomes. TLR9 belongs to the family of pattern recognition receptors that detect pathogen-associated molecular patterns. Activation of TLR9 leads to a downstream signaling cascade involving the myeloid differentiation primary response gene 88 (MyD88). This ultimately causes activation of nuclear factor κB (NF-κB) and production of pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 12 (IL-12). Secretion of these cytokines triggers both the innate and adaptive arms of the immune system.

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