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PMI 126 - Lecture 5

PMI 126 - Lecture 5 - PMI 126 LECTURE 5 Phagocytic cells of...

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PMI 126 – LECTURE 5 Phagocytic cells of the innate response: - monocytes/macrophages - polymorphonuclear leukocytes (neutrophils and eosinophils) o – normally stay in the blood unless there is tissue insult - dendritic cells All of these cell types possess numerous pattern recognition receptors (PRR) Ex. Macrophage receptors: - mannose receptor: lots of bacteria has mannose residue on the surface - LPS receptor (CD 14) - Glucan receptor - Scavenger receptor : identify self/nonself - TLR Receptors of Innate Immunity PAMP’s AND PRR’s - The receptors are constant - Their ability to distinguish themselves from pathogen is PERFECT (Never has autoimmune disease created by these receptors) PAMP’s: pathogen-associated molecular patterns: - Structure on micro that are conserved (ex. Lipopolysaccharide; component of a gram-negative bacteria cell wall) - A molecular structure that’s conserved in a group of pathogen. - Works well for pattern binding receptor. PRR’s : pattern-recognition receptors - encoded in germ-line (we all have genes that are conserved with a code of these receptors) - examples: o Toll like receptors (TLRs 1-12) o Scavenger receptors: receptor sees altered cells (injured cells that need to be eliminated) o Macrophage mannose receptor o NOD receptors (nucleotide-binding oligomerization domain): Found in cytosol Receptor in the cytoplasm of cells that binds bacteria product (general bacteria structure) NOD-1 & 2: cytosolic receptors o TREM: Triggering receptors expressed by myeloid cells ALL these receptors either expressed outside of cells or in the cytosol. = receptors inside the cells facilitate signal transduction to the nucleus of the cells o Mannose-binding lectin, Complement, C-reactive protein (CRP) These are “ secreted ” pattern-recognition receptors They bind on bacteria and facilitate eliminating of the bound bateria Opsonization : soluble pattern recognition receptors flowing around in extracellular space jump on the pattern they recognize. Once they are bound to the pathogen, phagocytic cells with the receptors for these secreted receptors grab it and engulf the bacteria along with the receptors Toll-like receptors: - Toll = weird in German slang - Discovered from fruit fly o Toll was identified as a gene important to development in Drosophila specifying correct dorsal-ventral patterning.
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o Mutations in Toll, or the signaling elements downstream, affected production of drosomycin and defense against fungal infections in adult flies. - The adaptor protein, MyD88, as a homolog in Drosophila. - Both IRAK and Pelle are serine kinases. - IKK and Cactus kinases are homologs. - IkB and Cactus, once phosphorylated, releases their homologous dimeric transcription factors , NFkB and DIF. Once pathogen with the structure that binds to Toll receptor in fruit fly => Eventually results transduction of nuclear transcription factor => Activate lots of transcription.
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