The innate immune system represents a first line of host defense against pathogens that surmount the body’s physical and chemical barriers (e.g., skin, ciliated epithelia, mucous membranes, stomach acids, and destructive enzymes in secretions). Innate defense mechanisms are mediated by cellular effector cells and noncellular effector molecules such as complement or lysozyme. Cellular elements of the innate immune system are generated in the bone mar row and migrate into blood and different tissues of the body. Tissue-residing (e.g., macrophages and dendritic cells ) and “mobile” phagocytic cells (e.g., neutrophils, eosinophils, and monocytes) as well as natural killer cells represent major cellular elements of the innate immunity [ 1 ].

After invasion of a pathogen the innate immune system is responsible to detect, contain, and ideally eliminate the thread immediately. Innate immunity has only a limited number of receptor molecules available to fulfill this task. Pathogens are detected through molecular-sensing surveillance mechanisms via pattern recognition receptors (PRRs), expressed by cells of the innate immune system either on the cell surface or in intracellular compartments (i.e., DNA/RNA sensors). Typical examples of PRRs are the transmembrane Toll-like receptors (TLRs) which recognize pathogen-associated molecular pattern s [PAMPs] that are shared by several pathogens (for example lipopolysaccharide expressed by all Gram-negative bacteria), thereby enabling the innate immune system to sense the occurrence of an infectious event [ 2 ]. For instance, TLR4 at the cell surface recognizes bacterial, whereas TLR9 is located intracellular and recognizes viral single-stranded RNA. PPRs sense danger signals and activate and augment proinflammatory gene expression in order to facilitate host defense capacity. Epithelial cells, fibroblasts, and vascular endothelial cells can also recognize PAMPs and activate innate immune cells when infected, stressed, or damaged. This is mediated by chemical messengers like cytokines and chemokines that are secreted by infected cells and/or innate immune cells to attract other resident and circulating innate cells to the site of infection.

Under some circumstances, pathogen elimination may be achieved by innate immune effectors alone without recruitment of a subsequent adaptive immune response . This can be accomplished by phagocytosis of pathogens and subsequent intracellular destruction within intracellular vesicles containing oxygen radicals and digestive enzymes. Additionally, pathogens can be destroyed by soluble chemical factors secreted by innate immune cells or generated in the liver. Complement represents the most important and effective soluble effector system of innate immunity [ 3 ]. Complement proteins circulate in the blood in an inactive form. Comparable to the coagulation system the 25 complement proteins are activated in cascades. When activated, complement components fulfill several effector functions including the recruitment of phagocytes, the opsonization of pathogens to facilitate phagocytosis, and the removal of antibody- antigen complexes. The complement system also strongly promotes the effector function of the adaptive immune response by mediating lysis of antibody-coated pathogens. The innate immune response is enforced by chemotactic stimuli, released by infected epithelial and endothelial cells or other innate immune cells to recruit additional circulating cells from the blood stream to the site of inflammation. While the defense provided by innate immune mechanisms in principle is sufficient to resolve an infection, during evolution many microorganisms have developed escape mechanisms to overcome the effectors of innate immunity. In most cases innate immunity will delay the invasion of pathogens, but intervention of the adaptive immune response is indispensable to overcome and finally clear an infection.

Although innate defense mechanisms are prearranged and fast reacting, they lack specificity and are not equipped to provide an immunological memory response. In consequence innate immunity alone is not sufficient for vaccine -related protective immune response s that depend strongly on the induction of immune memory responses [ 4 ]. Nevertheless, innate immunity fulfills an important role in the early detection of invading pathogens and subsequent activation of the adaptive immune response . The detection of pathogens and the phagocytosis of antigens by immature dendritic cells (DC) are important prerequisites to initiate adaptive immune responses. After ingestion of antigens immature DCs transform into antigen -presenting cells (APC) that migrate to the draining lymph node. The APC acts as a messenger to precisely defi ne the nature of the perceived danger and convey this information to secondary lymphoid organs, where they activate the relevant adaptive immune response. Although vaccines in the end target the adaptive immune system, vaccine antigens must be recognizable by innate immune cells.

References

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[1]. Moser M, Leo O (2010) Key concepts in immunology. Vaccine 28 Suppl 3:C2–C13

 [2]. Barton GM, Medzhitov R (2002) Toll-like receptors and their ligands. Curr Top Microbiol Immunol 270:81–92

[3]. Merle NS, Noe R, Halbwachs-Mecarelli L et al (2015) Complement system part II: role in immunity. Front Immunol 6:257

[4]. Leo O, Cunningham A, Stern PL (2011) Vaccine immunology. Perspectives Vaccinol 1:25–59