The FANTOM5 consortium recently characterized 38,554 robust human enhancers from 808 cell and tissue types using the Cap Analysis of Gene Expression technology. We used the distribution of guanine and cytosine nucleotides at enhancer regions to distinguish two classes of enhancers harboring distinct DNA structural properties. A functional analysis of their predicted gene targets highlighted one class of enhancers as significantly enriched for associations with immune response genes. Moreover, these enhancers were specifically enriched for regulatory motifs recognized by TFs involved in immune response. We observed that immune response enhancers were cell type specific, preferentially activated upon bacterial infection, and with long-lasting response activity. Looking at chromatin capture data, we found that the two classes of enhancers were lying in distinct topologically-associated domains and chromatin loops. Our results suggest that specific DNA sequence patterns encode for classes of enhancers that are functionally distinct and specifically organized in the human genome.