Innate Immunity
TLRs and Innate Immune Receptors and Molecules

Innate Immunity is the area of immunology which is comprised of cells and molecules which are non- specific to eliciting organism and are mobilized rapidly at initial signs of infection. Over the past 10 years Innate Immunity has become more extensively studied due to Innate Immunity linkage with host defense, importance in autoimmune disease etiology, inflammatory responses, and growing recognition of the importance of Innate Immune Receptors such as Toll-like Receptors, TLRs, which drive and control the adaptive immune response. In the area of innate immunity, response is often mediated through Pattern Recognition Receptors of which the most well-characterized are TLRs. There are at least ten TLRs in humans and thirteen TLRs in mice, although TLR10 is not expressed as a protein in mice due to a retroviral insertion sequence in the C-terminal half.¹
 

Innate Immunity systems of defense include natural anatomic barriers (skin), bodily fluids such as tears and saliva, humoral elements - the complement system and IL-1, and cells such as Dendritic Cells, NK cells, NKT cells, Neutrophils and Macrophages. These cells bear on their surface or in endosomes many TLRs. As part of the IL-1R family, TLRs recognize the pathogen associated molecular patterns (PAMPs) which are common to many different microbes including bacteria, viruses or fungi. When a PAMP ligand binds to a TLR, inflammatory signaling circuits are switched on through NF-kB or IRF pathways. The inflammatory signaling cascade composed of molecules including IL-1, TNFa, IL-6 among the more common, then initiates a specific adaptive immune response. In some cases innate immunity responses are triggered by conserved or endogenous ligands like nucleic acids, or proteins which are derived from effete or dying cells. In this scenario innate immunity is the response which is elicited by Damage Associated Molecular Pattern ligands or DAMPs. In the latter case innate immunity is a strong response to self antigens and a major causative process leading to autoimmune diseases - Rheumatoid Arthritis, Systemic Lupus Erythematosus to name the more well-known Autoimmune Diseases. Since TLRs are inextricably linked to the inflammatory signaling cascade, an enormous amount of research has been brought upon them and their role in autoimmune diseases.^2,3