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Review
. 2010 Jan 15;327(5963):291-5.
doi: 10.1126/science.1183021.

Regulation of adaptive immunity by the innate immune system

Akiko Iwasaki  1 , Ruslan Medzhitov
Affiliations
Review

Regulation of adaptive immunity by the innate immune system

Akiko Iwasaki et al. Science. .

Abstract

Twenty years after the proposal that pattern recognition receptors detect invasion by microbial pathogens, the field of immunology has witnessed several discoveries that have elucidated receptors and signaling pathways of microbial recognition systems and how they control the generation of T and B lymphocyte-mediated immune responses. However, there are still many fundamental questions that remain poorly understood, even though sometimes the answers are assumed to be known. Here, we discuss some of these questions, including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury.

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Figures

Fig. 1
Fig. 1
Cell extrinsic recognition of pathogens. Bacteria detected by dendritic cells through Toll like receptors (TLRs) are internalized into phagosome where bacterial antigens are processed for presentation on MHC class II. Bacterial antigens (red) and pathogen-associated molecular patterns (PAMPs) (blue) are present in the same phagosome, which indicates to the decdritic cell their common origin. TLR-mediated recognition of bacterial PAMPs promotes the selection of bacterial antigens for optimal presentation on MHC class II. TLR signaling also leads to the induction of costimulatory molecules and cytokines necessary for activation and differentiation of T lymphocytes.
Fig. 2
Fig. 2
Cell intrinsic recognition. Dendritic cells directly infected by viruses recognize pathogen-associated molecular patterns(PAMPs) (blue) within the cytosol via RIG-I like receptors (RLRs). Cytosolic viral proteins (red) are processed and presented on MHC class I (via the conventional ER pathway) or major histocompatability complex (MHC) class II (via autophagy). RLR signaling leads to the induction of costimulatory molecules and cytokines necessary for activation and differentiation of T lymphocytes. How the origin of antigen is established in this case is unclear. In the case of MHC class I pathway, this may depend on the abundance of viral antigens. In the case of MHC class II pathway, it may depend on targeting of viral antigens by the autophagy machinery.
Fig. 3
Fig. 3
Cell extrinsic recognition of infected cells. A virally-infected non-antigen presenting cells recognizes pathogen-associated molecular patterns (PAMP) (blue lines indicate viral nucleic acids) within the cytosol via the RIG-I-like receptors (RLRs), leading to secretion of type I interferons (IFNs) and other factors that activate dendritic cells. Infected dead cells are taken up by non-infected dendritic cells and viral PAMPs (blue) are recognized through endosomal Toll like receptors (TLRs). Viral antigens (red) are processed and presented on major histocompatability (MHC) class II (via the conventional endosomal pathway) or MHC class I (via cross-presentation). TLR signaling leads to the induction of costimulatory molecules and cytokines necessary for activation and differentiation of T lymphocytes.
Fig. 4
Fig. 4
Proposed consequences of Toll like receptor (TLR) recognition of exogenous versus endogenous ligands. TLR engagement by exogenous (A) or endogenous (B) agonists leads to signaling from distinct subcellular compartments (indicated by blue and green, respectively) and/or engagement of coreceptors. Consequently, exogenous ligands induce transcription of genes leading to inflammation, tissue repair and the initiation of adaptive immunity (A). In contrast, endogenous ligands induce TLR signaling for activation of inflammation and tissue repair but not the initiation of adaptive immunity (B).
See this image and copyright information in PMC

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