TOLL LIKE RECEPTOR 2 TLR2 LEVELS SHOW AGE-RELATED EFFECTS IN HEALTHY ADULTS

CHAPTER 1
1.1 INTRODUCTION
Toll-like receptors (TLRs) are transmembrane proteins. They form a part of the Toll/interleukin-1 (TIR) super family that includes the interleukin-1 receptors (IL-1Rs) because of the shared homology of their cytoplasmic domains. However, the extracellular domain of IL-1Rs consist of an immunoglobulin G (IgG) domain while TLR extracellular domains are made up of tandem repeats of leucine-rich regions termed leucine-rich repeats. Macrophages initiate the innate immune response by recognizing pathogens, phagocytizing them and secreting inflammatory mediators. An effective immune response requires that macrophages recognize pathogen-associated molecular patterns (PAMPs) that distinguish the infectious agents from ‘‘self’’ and in addition discriminate among pathogens. A novel family of receptors, the Toll-like receptors (TLR), has been demonstrated to identify pathogen-associated molecular patterns (PAMPs) on infectious agents and discriminate between pathogens (Janeway and Medzhitov, 2002).
Central to this role is the broad specificity with which they can detect pathogen-associated patterns and danger associated patterns via the pattern recognition receptors (PRRs) they express. Several families of PRRs have been identified including Toll-like receptors (TLRs), C-type lectin-like receptors, retinoic acid-inducible gene-like receptors and nucleotide-binding oligomerization domain–like receptors. TLRs are one of the most largely studied families of PRRs. The binding of ligands to TLRs on antigen presenting cells (APCs) mainly dendritic cells leads to APC maturation, induction of inflammatory cytokines and the priming of naive T cells to drive acquired immunity (Janeway and Medzhitov, 2002). Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed on sentinel cells such as macrophages and dendritic cells, which recognize structurally conserved molecules derived from microbes (Janeway, 1989). Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses. Toll-like receptors are a family of type I transmembrane pattern recognition receptors (PRRs) that sense invading pathogens or endogenous damage signals and initiate the innate and adaptive immune response. Furthermore, Toll-like receptors ligation triggers several adapter proteins and downstream kinases, leading to the induction of key pro-inflammatory mediators but also anti-inflammatory and anti-tumor cytokines (Beck and Habicht,1996).The result of this activation goes beyond innate immunity to shape the adaptive responses against pathogens and tumor cells, and maintains host homeostasis via cell debris utilization (Beck and Habicht,1996).
The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13, though the latter three are not found in humans. Of the human TLRs, TLR1, 2, 4, 5, 6, and 10 are expressed on the cell surface and primarily recognize microbial membrane and/or cell wall components, while TLR3, 7, 8, and 9 are expressed in the membranes of endolysosomal compartments and recognize nucleic acids.TLR2 is one of the toll-like receptors and plays a role in the immune system. TLR2 is a membrane protein, a receptor, which is expressed on the surface of certain cells and recognizes foreign substances and passes on appropriate signals to the cells of the immune system. TLR2 recognizes the largest number of microbial ligands, including various fungal, gram-positive and mycobacterial components such as peptidoglycans, lipoarabinomannan and bacterial lipoproteins (Bell et al; 2003).

1.2 AIMS AND OBJECTIVES OF STUDY
The aims and objectives of this study were to;
Measure the levels of Toll-like receptor 2 (TLR2) in the plasma of healthy adults in the population by the Enzyme linked immunosorbent assay (ELISA) technique.
Assess if the TLR2 levels were gender dependent and
Determine if age has an influence on TLR2 levels.