Immunology Notes

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Microbiology and Immunology
Microbiology and Immunology 3300B
Rodney Dekoter

Immunology NotesSept 2212 Innate receptorsInherited in the germline expressed by all cells of a particular type triggers immediate response recognize broad classes of pathogens degenerate and interact with a range of molecular structures PAMPs of a given type Adaptive receptors Encoded in multiple gene segments require gene rearrangement clonal distribution and able to discriminate between closely related molecular structures Pathogenassociated molecular patterns PAMPs Molecules found only in pathogens Individual PAMPs will be present on a broad range of pathogens common to lots of different pathogens They are evolutionarily conserved wont change over time because this would be harmful to the pathogen Common bacterial PAMPs The cell walls of grampositive bacteria contain lipoteichoic acid and peptidoglycan The cell walls of gramnegative bacteria contain lipopolysaccharide These components are not found in animal cells In human DNA the C of CG pairs is methylated so we can recognize our own DNA In pathogens CG isnt methylated so we know its foreign Other PAMPs are flagellin and metabolites fMLPfMet is an amino acid present in prokaryotes but not eukaryotes Viral PAMPs Viruses contain dsRNA but humans do not They also contain unmethylated CpG motives in their DNA Our immune systems can also look for endosomal ssRNA because RNA in humans is only found in the nucleus and cytoplasm Fungal PAMPs Fungi contain zymosan and glucan polysaccharide in their cell walls and they contain the protein profiling Humans dont have these things Pattern recognition receptors PRRs Receptors in our immune system that bind to PAMPs They are germline encoded inherited not recombined There are two major types Tolllike receptors TLRs and nonTLRs everything else Toll is required for antifungal responses in drosophila Normally flies have a smooth thorax but if they are missing the Toll receptor fungus infects their thorax They have a reduced ability to fight infection There are 10 expressed TLR genes in humans and each is devoted to recognizing a distinct set of molecular patterns that are not found in healthy vertebrate cells PAMPs Some TLRs are present on the plasma membrane and others are located intracellularly in the membranes of endosomes The ones located on endosomes are there because viruses are brought into the cell through endosomes Some TLRs function independently with other TLRs or with accessory molecules TLRs contain LRR regions that form a Ushape This is the region that binds to pathogen ligands TLRs are activated when a ligand binds to them inducing them to form dimers The TIR domains of TLRs interact together forming the dimer Not all cell types express all TLRs They are placed where pathogens are most likely encountered Innate immune recognition by mammalian Tolllike receptors TLRs Tolllike receptor LigandCellular distributionLipomannans mycobacteria Monocytes dendritic cells mast cells TLR1TLR2 heterodimer Lipoproteins eosiniophils basophils Lipoteichoic acidsCellwall glucans bacteria and fungi TLR2TLR6 heterodimer Zymosan fungi
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