Chapter 19 : Innate Immunity in Infections

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This chapter addresses the current knowledge pertaining to innate immunity and , and highlights important areas of future research. With a better understanding of the intricacies of immunity comes the realization that our host defenses cannot be strictly divided into innate and adaptive systems. Host defense mechanisms relevant to protection against a gastrointestinal infection such as include the multiple cellular and soluble factors. Although the interplay between many of these components and are not fully understood, the chapter reviews the current knowledge and outlines areas in need of further study. Innate immune defenses found in the gastrointestinal tract appear extremely effective in limiting to the gut. The direct antimicrobial activities of these phagocytes is attributable to production of antimicrobial peptides/proteins, ROS, and RNS (the latter mainly by mononuclear phagocytes and/or macrophages). The sequencing of several genomes and improved mutagenesis techniques can facilitate molecular studies of particular genes with specific innate immune components. From the point of view of the host, genomewide association studies of genetic polymorphisms associated with alterations in host defense functions may provide insight into those genes that are important for defense against infection.

Citation: Iovine N. 2008. Innate Immunity in Infections, p 333-350. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch19
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Image of Figure 1.
Figure 1.

Production of nitric oxide from dietary nitrate. Nitrate in foods such as meat is ingested, is absorbed in the intestine, and enters the systemic circulation. The salivary glands concentrate the nitrate from blood and secrete it into the saliva. On the tongue, particularly in the area of the posterior papillae, facultative microbes that express nitrate reductase convert nitrate to nitrite. This nitrite is swallowed and interacts with hydrogen ions in the stomach to produce nitric oxide. Although dietary nitrate may be directly reduced on the tongue to form nitrite, the high nitrate concentration in saliva is the major source of the nitrite that enters the stomach.

Citation: Iovine N. 2008. Innate Immunity in Infections, p 333-350. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch19
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Image of Figure 2.
Figure 2.

Innate defenses active in the intestinal tract. Defenses present in the small and large intestine are depicted schematically. Particularly in the lumen of the large intestine, the normal biota occupies a niche that otherwise might be available to Mucous layer mucins may exert an antimicrobial effect. Coating of with breast milk fucosylated sugars may impede interaction of with H(O) antigens on intestinal epithelium. Bile acids exert an antimicrobial, detergent-like effect. Dendritic cells (DC) send cellular extensions into the intestinal lumen to sample antigens, leading to DC activation. organisms that evade these mechanisms are challenged by defenses present in the epithelium itself. Toll-like receptor 4 (TLR4) senses LPS and triggers an NF-κB-dependent cascade, resulting in production of proinflammatory molecules such as IL-8. Upon epithelial cell invasion, interaction of peptidoglycan with NOD1 augments induction of β-defensins with known antimicrobial activity against organisms that survive these defenses may enter the submucosa, where phagocytes recruited and activated by IL-8 produce potent molecular defenses: NOS2-derived nitric oxide (NO) and other reactive nitrogen species principally from macrophages (Mθ) and NADPH oxidase (NADPH ox)-derived superoxide (O2-) and other ROS principally from polymorphonuclear neutrophils (PMN). The latter also produce cationic antimicrobial peptides and proteins (CAPPs) including defensins, and may exert killing after phagocytosis or in the extracellular space after degranulation. Similarly, highly diffusible NO may effect killing outside of the Mθ. Finally, organisms that enter the systemic circulation are faced with the potent antimicrobial activity of acute-phase proteins, as well as complement, in addition to circulating PMNs.

Citation: Iovine N. 2008. Innate Immunity in Infections, p 333-350. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch19
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Image of Figure 3.
Figure 3.

Key and proposed elements of innate immune defense against infection. Innate immune components for which good evidence exists of their contribution to defense against infection in humans are shown in bold. Those components that are proposed to play a role in defense against and that warrant further study are shown in italics. CRP, C-reactive protein; Fe, iron; NO/RNS, nitric oxide/reactive nitrogen species.

Citation: Iovine N. 2008. Innate Immunity in Infections, p 333-350. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch19
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Generic image for table
Table 1.

Immune components relevant to innate defense against gastrointestinal infections

Citation: Iovine N. 2008. Innate Immunity in Infections, p 333-350. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch19
Generic image for table
Table 2.

Acute-phase proteins relevant to gastrointestinal infections

Citation: Iovine N. 2008. Innate Immunity in Infections, p 333-350. In Nachamkin I, Szymanski C, Blaser M (ed), , Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815554.ch19

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