Chapter 10: Inflammation and Shock
Cells of the monocyte-macrophage lineage recognize antigens by which of the following mechanisms?
(B) Toll-like receptors (TLR)
(B) Phagocytic cells such as macrophages, monocytes, and neutrophils compose the innate immune system. Innate immunity represents a preexisting resistance to antigens, not requiring a prior exposure. This contrasts with acquired immunity, which depends on repeated contact with the antigen to augment the immune response. Although the innate immune system commences an inflammatory reaction, its interaction with the T and B cells of acquired immunity propagate and strengthen the response.
The specificity of the response to an antigen is mediated by the toll-like receptors (TLRs), a family of pattern recognition molecules. This family of transmembrane protein receptors, present on the surface of macrophages and monocytes, binds various antigenic products such as bacterial flagellin and DNA. Each of the 10 known TLRs detects a particular antigen; for example, TLR-3 and TLR-4 bind viral double-stranded DNA and lipopolysaccharide (LPS), respectively. Following the attachment of LPS to the LPS-binding protein, TLR-4, in conjunction with MD2 and the soluble protein CD14, activates a cascade of intracellular proteins, including the toll/IL-1 receptor–associated protein and the mitogen-activated protein (MAP) kinases, ultimately resulting in activation of nuclear factor-κB (NF-κB) (see Fig. 10-1). This transcription factor promotes the expression of numerous inflammatory mediators.
FIGURE 10-1. The toll-like receptor (TLR) binds lipopolysaccharide (LPS). LBP, lipopolysaccharide-binding protein. From Brunicardi FC, Andersen DK, Billiar TR, et al. (eds.), Schwartz’s Principles of Surgery, 9th ed. New York, NY: McGraw-Hill Professional; 2009:Fig. 2-13.
Lipid A is the toxic moiety of LPS, the characteristic outer membrane component of gram-negative bacteria. The T-cell receptor detects antigens in the context of antigen-presenting cells, phagocytic cells that expose antigenic components on their surface. Immunoglobulin G is generated by B cells in response to a specific antigen; this antibody may appear on the surface membrane of B cells or free within the blood. IL-2 is a cytokine product of the inflammatory process.
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