Specialised chemical messengers, including cytokines and chemokines, are secreted by stressed/damaged cells and innate immune cells to attract other resident and circulating innate cells to the site of infection. Cells dying due to infection also release other small molecules, such as urea, which alert DCs. The local reactogenicity observed following vaccination probably reflects the induction of local inflammatory responses, which are important

in the initiation of a successful immune response. Appendices, Supplementary Table 1 shows some examples of the innate biological consequences of signalling through PRRs. The downstream adaptive responses triggered by these signals are determined by the intracellular signalling pathway into which the signal feeds. Further fine-tuning of these responses learn more to specific outcomes is believed to be achieved via the recruitment of specific

intracellular adaptor molecules, which modify and manipulate the signal sent to the nucleus of the innate cell to tailor the profile of gene expression. Redundancy exists in pathogen detection systems, as multiple receptors may recognise the same pathogenic structure and, conversely, a single receptor may be capable of delivering more than one signal to the host cell. Overall, the integration of these signals by APCs leads to their activation. This enables them to act as messengers to precisely define the nature of the perceived danger and convey this information to the secondary lymphoid organs, where they interact with, and specifically GDC-0068 price activate, the

relevant adaptive immune response. Under some circumstances, pathogen clearance may be achieved by innate immune effectors without activation of an adaptive immune response. Activated innate cells act as phagocytes, engulfing and destroying the pathogen within intracellular vesicles containing digestive enzymes. To be efficient, this response requires both the recruitment and activation of phagocytes at the site of infection, a process Orotidine 5′-phosphate decarboxylase often referred to as the inflammatory response. Cells residing in proximity to the infection site are activated upon recognition of PAMPs, and secrete a large array of soluble mediators, including chemokines and cytokines (Figure 2.5). Chemokines behave as chemoattractants (Appendices, Supplementary Table 2), favouring the recruitment of innate immune cells to the site of infection, while cytokines (including tumour necrosis factor and interferons) (Appendices, Supplementary Table 5) act by increasing the phagocytic activity of cells. Innate immune cells also produce a series of soluble chemical factors (such as peptides) that are able to directly target the invading microbes. Additionally, antigens are taken up by innate cells, with immature DCs the most specialised among them. The antigen is subsequently processed and the DC differentiates into an APC.