Materials that harness and modulate the immune system
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Immune system introduction The mammalian immune system is a highly complex, yet organized, network of organs, cells, and biomolecules whose primary function is to defend the body from any recognized foreign entity, including viruses and bacteria.1 This defense system deploys two concerted sets of mechanisms to shield the body from would-be invaders: (1) the antigen-independent, nonspecific innate immune response that is activated immediately upon pathogen invasion, and (2) the temporally delayed, antigen-specific, adaptive immune response. Innate immunity employs a set of instant, protective measures that are specific to broad classes of pathogenic molecules. For instance, the skin and mucosal linings are central to the innate immune system forming a protective barrier from numerous pathogenic agents.1,2 Additionally, innate immune responses include precise elements that allow for efficient molecular recognition and removal of non-self-entities (identified as not belonging to the host) and, further, engagement of the adaptive arm of the immune system via co-stimulatory signaling.1,2 Essential to these responses are molecules of the complement system, chemokines and cytokines such as interferons, as well as cells such as neutrophils, macrophages, natural killer cells, and of particular note, dendritic cells (DCs) (see review on innate immunity in References 1 and 2).
The adaptive immune system, found only in vertebrates, is thought to be born out of evolutionary necessity and is involved in the development of long-term memory for newly encountered antigens.3 Adaptive immunity is characterized by (1) an extraordinary repertoire of receptor molecules that result from somatic recombination (a mechanism of genetic recombination in the early stages of immunoglobulin [Ig] and T-cell receptors [TCRs] production of the immune system) and (2) immunological memory. With a diverse repertoire of molecules, which are typically on the cell surface and/or secreted by T cells (lymphocytes with multiple subsets, including those that attack infected or cancerous cells, direct the immune responses, and curb excessive immune reactions) and B cells (lymphocytes that primarily differentiate into plasma cells that secrete antibodies to attack foreign antigens), the adaptive arm of the immune system is highly effective in specifically tailoring immune reactions toward a newly defined pathogenic threat, while reducing any potential collateral damage to host tissue. Moreover, clonal expression and selection generate mechanisms by which long-term memory of the immune system is developed and preserved, which provides protective immunity from subsequent challenge by the same pathogen.4 Together with T cells and B cells, the central effectors for adaptive immune responses include immunoglobulins and a wide array of cytokines. Figure 1 illustrates a simplified
Jamal S. Lewis, University of Florida, Gainesville; jamalslewis@ufl.edu Krishnendu Roy, University of Texas at Austin; [email protected] Benjamin G. Keselowsky, University of Florida; bkeselows
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