Pattern Recognition Receptors Proteins


 Pattern Recognition Receptors Proteins Background

The innate immune system of multicellular organisms relies on sentinel tissues to detect localized or systemic infections by pathogens. The tissues include barrier epithelia (skin), blood cells, and more specialized organs. These tissues express proteins at the cell surface that can recognize pathogens by direct contact or secrete proteins that bind to the pathogen. These host proteins that can bind directly to molecules from pathogens are termed pattern recognition receptors (PRR). The term implies that the proteins bind to molecules that are common to broad classes of pathogens, and the molecule to which it binds is essential to the pathogen and therefore cannot evolve so much as to avoid immune recognition. Pattern recognition receptors are germline encoded and do not undergo somatic mutation to achieve specificity. Pattern recognition receptors have evolved to recognize pathogenic ligands and can discriminate molecules as foreign and dangerous.

Upon recognition of a pathogenic ligand, a pattern recognition receptor can signal to initiate an immune response. Recognition precedes the effector stage of the immune response. The host then utilizes several mechanisms to kill and dispose of the pathogen. Drosophila relies on the activity of antimicrobial peptides, melanization, and phagocytosis to rid themselves of pathogens.

In vertebrates, pattern recognition receptors are also utilized to activate the innate immune response to combat infections. Vertebrates also have an adaptive immune response that relies centrally on B and T cells to generate additional specificity and immunological memory towards combating pathogens. However, the adaptive immune response depends on activation of the innate immune response, and therefore upon pattern recognition receptors. Dendritic cells, B cells, and macrophages belong to a class termed antigen presenting cells (APCs). APCs express pattern recognition receptors and upon binding to a pathogenic ligand, the receptors signal the APC to undergo maturation and to express co-stimulatory molecules at the cell surface. APCs process and present pathogenic antigens through the major histocompatibility complex (MHC). T cells that recognize the MHC presented pathogenic antigen are also signaled by the co-stimulatory molecules on the APC surface. T cells that receive signals through both the T cell receptor (TCR), and the co-stimulatory receptors, are activated to proliferate and respond. T cells that recognize MHC presented pathogenic antigens through the TCR, but receive no co-stimulatory signal, die or become anergic. Therefore, T cell responses ultimately depend on APCs' pattern recognition receptors being activated by pathogenic ligands, and APCs' subsequent maturation and co-stimulatory signals at the cell surface. It should be noted that pattern recognition receptors are also expressed by cells other than APCs, and may also function in additional roles.

In flies and vertebrates, pattern recognition receptors play a fundamental role in recognizing pathogens and initiating immune responses. Several classes of pattern recognition receptors have been identified to date in both Drosophila and in vertebrates, and potentially several more remain to be discovered. The types of pattern recognition receptors discussed in the subsequent sections are confined to those proteins that are thought to directly interact with pathogenic molecules, and to have a role in subsequent immune signaling.