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DNA and the Immune System

David S. Pisetsky, MD, PhD
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Durham Veterans Administration Medical Center, Duke University Medical Center, Durham, NC 27705 Grant Support: In part by a Veterans Administration Merit Review grant; by the Veterans Administration Research Center on AIDS and HIV Infection; and by grant AR-39162 from the National Institutes of Health. Requests for Reprints: David S. Pisetsky, MD, PhD, Durham Veterans Administration Medical Center, Box 151G, 508 Fulton Street, Durham, NC 27705.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;126(2):169-171. doi:10.7326/0003-4819-126-2-199701150-00015
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Deoxyribonucleic acid (DNA) conveys an enormous amount of information because of the myriad ways in which its four bases can be arranged. As a genetic blueprint, this information provides elaborate instructions for the structure of proteins and the regulation of their expression. Encoded in DNA, however, is information of a fundamentally different kind. As provocative new data indicate, DNA from bacteria has sequences that can instruct the immune system to distinguish “foreign” from “self.” These sequences, which bear characteristic motifs, can trigger innate immunity and are important not only in host defense but in the burgeoning use of DNA to prevent and treat disease [1].

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dna ; immune system

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Figure 1.
Immunologic activities of bacterial DNA.

The immunologic properties of bacterial DNA result from CpG motifs and may influence the human immune system in several settings. A. In normal immunity, bacterial DNA can nonspecifically stimulate the immune system by activating cytokine production and B-cell immunoglobulin secretion. B. Normal humans produce antibodies to DNA that target specific sequences exclusive to bacterial DNA. In persons with systemic lupus erythematosus, antibodies to DNA bind conserved backbone determinants present on both bacterial and mammalian DNA. C. Antisense agents are small oligonucleotides that can block specific gene expression. Because of their sequence and backbone modifications (shown schematically by the zig-zag line), some antisense compounds can also mimic bacterial DNA and nonspecifically promote B-cell activation (see panel A). D. The DNA vaccines are plasmid constructs encoding a foreign protein that is then released into the immune system of the host, where it serves as an antigen that stimulates targeted protective immunity. These plasmids are taken up by cells and lead to effective B-cell and T-cell responses. The potency of these vaccines may be nonspecifically enhanced by the presence of CpG motifs through mechanisms similar to those shown in panel A. Ag = antigen; IFN = interferon; Ig = immune globulin; IL = interleukin; NK = natural killer; SLE = systemic lupus erythematosus.

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