Antibodies from IMGENEX: Toll-like Receptors

 The guardians of innate immunity Innate immunity as the first line of defense The innate immune system is an ancient mechanism of host defense in almost all multicellular organisms from plants to humans. In invertebrates, it is the only mechanism of defense against pathogens but in higher vertebrates it is the first line of defense. The role of the innate immune system is to distinct between self and non-self and between pathogenic and nonpathogenic microbes, it also plays an important role in triggering and optimization of the adaptive immune response. This remarkable system allows an immediate nonspecific response against micro-organisms while the adaptive immune system mounts a specific response against the invading pathogen during the late phase of infection. Pattern Recognition Receptors The cornerstone of the innate immune system is composed of germline-encoded receptors called pattern recognition receptors (PRR), in which the Toll-like receptors belong. These PRRs are activated upon recognition of "pathogen-associated molecular patterns' or PAMPs. PAMPs are molecular structures shared by large groups of pathogens not normally present in the host.  1. Molecular model system must be shared by large groups of pathogens and therefore should represent general trends rather than specific structures. 2. They must be retained products of microbial metabolism that are not subject to antigenic variability. Although the immune system selects against these models, the pathogens can not "change" because they are essential to the survival or pathogenicity of microorganisms. Any attempt to change them could be lethal to the microbe or render it non-pathogenic. 3. The structures recognized must be absolutely distinct from self-antigens. The major consequence of this requirement is the ability of the innate immune system distinguish between self and non-self. Characterized PAMPS particular cell wall constituents such as lipopolysaccharide (LPS), peptidoglycan (PGN), lipoteichoic acid (LTA) or lipoarabinomannan (LAM), but also single or double stranded RNA and unmethylated CpG DNA . Overview of Toll-like receptors The TLRs owe their name to a receptor called Toll closely related, first identified in Drosophila. The first member of the Toll family was identified in Drosophila in 1988 during a screen for embryonic polarity genes. Drosophila Toll receptors cause an induction of innate immune responses of a first link to a tube adapter, which is a functional homologue of mammalian MyD88. This tube is connected to the kinase Pelle, a homologue of IRAK, and after a cascade of reactions leading to the transcription of genes that modulate and mediate the activation of antimicrobial pathways that directly kill the pathogen.