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Key Points Nanotechnology makes use of the unique properties of objects that function as a unit within the overall size range of 1 to 1,000 nanometres, which is on the same scale as for many biological structures such as antigens, receptors, subcellular components of the immune system and microbes. The engineering of nanoscale compounds by the modification of properties such as nanoparticle size, shape, charge, porosity, surface area and hydrophobicity holds great promise for the development of immune response modulators and vaccines.The enhancement of the immune response by nanoparticles can be achieved through innate immune potentiation or by the enhanced delivery of antigens. Virus-like particles activate the innate immune response via Toll-like receptors and the repetitive display of antigens, whereas nanogels and cationic liposomes are examples of vaccine carriers.The molecular pathways involved in immune activation by nanoparticles are diverse and might include the upregulation of homing receptors such as CC-chemokine receptor 7, co-stimulatory molecules including CD40, CD80 and CD86, as well as increased cytokine production. Enhanced delivery by nanoparticles might induce apoptosis or necrosis.The suppression of the immune response can be achieved through direct immunosuppression or by the delivery of immunosuppressants. Fullerenes have a direct immunosuppressive effect but can also deliver immunosuppressive drugs, as can dendrimers, polymers, and liposomes.The molecular pathways involved in immunosuppression might include increased expression of cyclooxygenase 2, prostangandin E2 and interleukin-10 (IL-10), and apoptosis. The delivery of immunosuppressants results in a decreased response to IL-2 with sirolimus, in the downregulation of nuclear factor-kB with steroids, and in the upregulation of forkhead box P3 (FOXP3), which causes an increased regulatory T cell activity when self antigens are presented.Nanotechnology will continue to provide remarkable insights into the nature of the immune response. The application of nanotechnology to immunology might also affect new strategies to prevent or to treat human diseases. Supplementary information The online version of this article (doi:10.1038/nri3488) contains supplementary material, which is available to authorized users., This Review describes the different types of nanotechnologies that can be used to target the immune system. The authors explain how the unique properties of different nanostructures can be used to either enhance or to suppress immune responses, and they discuss the promise of these strategies for developing more effective immunotherapies. Supplementary information The online version of this article (doi:10.1038/nri3488) contains supplementary material, which is available to authorized users., Nanotechnology uses the unique properties of objects that function as a unit within the overall size range of 1–1,000 nanometres. The engineering of nanostructure materials, including nanoparticles, nanoemulsions or nanotubules, holds great promise for the development of new immunomodulatory agents, as such nanostructures can be used to more effectively manipulate or deliver immunologically active components to target sites. Successful applications of nanotechnology in the field of immunology will enable new generations of vaccines, adjuvants and immunomodulatory drugs that aim to improve clinical outcomes in response to a range of infectious and non-infectious diseases. Supplementary information The online version of this article (doi:10.1038/nri3488) contains supplementary material, which is available to authorized users.

Nature Reviews Immunology 13, 592–605 (2013) In the version of this Review that was initially published, the reference citations in Tables 1–3 were not accurate. This error has been corrected in the online HTML and PDF versions of the article. Nature Reviews Immunology apologizes for this error.