Microbes of immune cells needed for the PAMP-specific

Microbes induce an array of innate immune responses, one of the early responses is a result of the activation of the non-clonally expressed Pattern recognition receptors (PRRs); such receptors recognise and engage highly conserved molecular patterns such as lipopolysaccharides, found in large groups of pathogens: bacteria, fungi, viruses and parasites, Pathogen-associated molecular patterns; aswell as damage-associated molecular patterns from damaged endogenous cells and tissue, these activate TLRS and cause subsequent activation of a conserved signalling pathway that results in the upregulation of cytokines, chemokines, antimicrobials, and antiviral genes. PRRs are expressed by most innate immune effector cells, including; myeloid white blood cells and subsets of the three types of lymphocyte: B-cells, T-cells and NK cells. The most extensively studied PRR-subtype is the germ-line encoded Toll-like receptor as demonstrated with Drosophila studies, which is a type 1 transmembrane protein that is characterised by an extracellular ectodomain containing leucine-rich repeats (LRRs) that mediates the recognition of their respective PAMPS and a cytoplasmic tail that contains a conserved region called the Toll/IL-1 receptor (TIR) domain, which is required for initiating downstream signalling pathways, the majority of this TLR signalling activates the transcription factor NFkB via MyD88 adaptor protein, making MyD88 a central node of inflammatory pathways. However, the TLR-3 pathway only interacts with TIR domain-containing adaptor-inducing IFN-b. Activation through these adaptor molecules allow NFkB, which is made up of two subunits, P50 and P65, to cause the upregulation of the expression of immune cell related genes, resulting in the production of type 1 interferons, pro-inflammatory cytokines and chemotactic factors; thus causing the proliferation of immune cells needed for the PAMP-specific adaptive immune response. 10 TLRs have been identified in humans; TLR1, TLR2, TLR4, TLR5 and TLR6 are located on the plasma membrane, but TLR3, TLR7, TLR8 and TLR9 are endosomal, all of which share this common structure. Other PRR families include C-type lectin receptors, nucleotide oligomerisation receptors and RIG-1 like receptors, which like toll-like receptors can be placed both on the cell surface and within endosomal vesicles, this strategic localisation within the cell allows the recognition receptors to detect extracellular and intracellular pathogens, respectively. 

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