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228 Cards in this Set
- Front
- Back
What are the characteristics of a Gm+ bacteria?
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Thick peptidoglycan layer, stains purple in Gram stain, single inner membrane, more teichoic acids, Ex. S.aureus
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What are the characteristics of a Gm- bacteria?
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Thin peptidoglycan layer, stains red in gram stain, inner and outer membranes, cont. LPS Ex. E.coli
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CWD
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Cell wall defective - change or partial loss of cell wall
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L-form
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no cell wall
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Teichoic acids
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acidic polysaccharide
covalently linked to NAM give typical negative charge more abundant Gram+ bacteria can act as a barrier to penetration of negatively charged molecules |
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Phosphonomycin/Fosfomycin
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Blocks the conversion from NAG to NAM during the production of peptidoglycan layer.
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D-cycloserine
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Blocks the addition of D-ala by racemase enzyme during peptidoglycan layer production
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Bacitracin
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Inhibits the recycling of undecaprenyl-P which flips and transfers the peptidoglycan layer building block to the outside of the the layer for addition.
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Vancomycin
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Binds the substrate/building block for peptidoglycan layer synthesis and stericly inhibits the binding of PBP and there for inhibits transglycosylation and transpeptidation
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Beta-lactams
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Ab, such as penicillin, that binds PBP and inhibits transglycosylation and transpeptidation
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What are the characteristics of a Gm+ bacteria?
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Thick peptidoglycan layer, stains purple in Gram stain, single inner membrane, more teichoic acids, Ex. S.aureus
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What are the characteristics of a Gm- bacteria?
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Thin peptidoglycan layer, stains red in gram stain, inner and outer membranes, cont. LPS Ex. E.coli
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CWD
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Cell wall defective - change or partial loss of cell wall
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L-form
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no cell wall
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Teichoic acids
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acidic polysaccharide
covalently linked to NAM give typical negative charge more abundant Gram+ bacteria can act as a barrier to penetration of negatively charged molecules |
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Phosphonomycin/Fosfomycin
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Blocks the conversion from NAG to NAM during the production of peptidoglycan layer.
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D-cycloserine
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Blocks the addition of D-ala by racemase enzyme during peptidoglycan layer production
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Bacitracin
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Inhibits the recycling of undecaprenyl-P which flips and transfers the peptidoglycan layer building block to the outside of the the layer for addition.
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Vancomycin
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Binds the substrate/building block for peptidoglycan layer synthesis and stericly inhibits the binding of PBP and there for inhibits transglycosylation and transpeptidation
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Beta-lactams
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Ab, such as penicillin, that binds PBP and inhibits transglycosylation and transpeptidation
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LPS
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Lipo-polysacharride, responsible for endotoxic shock, assoc. with Gm- bacteria. 3 parts: Lipid A - conserved on all lps, endotoxic component; Core polysaccharide - variable; O side chain - long repeated subunits and specific to bacterial species.
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Why can gm- bacteria be more intrinsically resistant to Ab?
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Because their outer memb. can serve as a barrier, forcing molecules to go through porins that don't allow large and/or uncharged molecules
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How does sugar enter the cell?
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By group translocation, a process powered by the energy in phosphoenolpyruvate. It results in the phosphorylation of the sugar as its brought in.
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Polymyxin
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Only Ab to target the memb., affinity for LPS and Phosphattydylethanolamine. Binds bc of fatty acid tail -> better affinity for Gm-. Kills Gm- well, Gm+ ok. Induces autolytic mechanisms at high concentrations, destroys non-growing cells
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Cationic Peptides
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Binds bacterial proteins, interchelate into membrane, self assembles, forms pore and lyses cells. Hard to get resistance to.
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What are the functions of a capsule?
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mediate adherence; protect from phagocytosis, Ab, and dessication.
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What are the functions of a slime layer/matrix?
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Reserve of carbs for metabolism; formation of biofilms, protection from phagocytosis
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What are the functions of Pili/fimbriae?
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attachment, adherence, conjugation, motility (type IV pilus)
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Novobiocin and Ciprofloxacin
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Antibiotic that keeps the DNA gyrase complex from unwinding the DNA
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Quinolines and floroquinolines
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Recognize and bind gyrase-ATP complex, stabilizes it and keeps cleavage from occuring. Replication machinery collides and blocks replication.
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What is a way for identifying dental bacterial species?
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PCR of 16S rRNA to amplify, sequence and compare in a database.
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What is a homolactic bacteria?
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One whose only fermentation product is lactic acid. Stretococci and Lactobacilli
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What is a heterolactic bacteria
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Ferments to lactic acid, ethanol, CO2 and H+
some Lactobacillus |
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What is a mixed acid bacteria?
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Production of ethanol, 2,3butanediol, succinate, lactate, acetate, formate, H2 and CO2.
Enteric bacteria |
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What is a clostridial spp.?
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Produces butyric acid, butyl alcohol, acetone, ethanol, H2 and CO2.
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Citrate Test
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Citrate is a three carbon sugar, if metabolized, by products raise pH and change color from green to blue.
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API strips
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tests various sugars for fermentation by bacteria in question and indicates production of acid and/or gas or neither.
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Voges-Proskauer Test
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Tests for production of 2,3 butanediol or acetoin, + if solution turns red. Mixed acid if +.
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ONPG assay
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ONPG is similar to lactose, tests for beta-galactosidase which forms galactose from Beta-galactose which is a product of lactose cleavage.
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What are the more common terminal electron acceptors for anaerobic respiration?
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NO3 and thiosulfate
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Oxidase Test
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Tests for cytochrome c (respiration). Add drop of TMP to colony, and if it oxidizes it and turns the colony blue or brown, cyt c is present. Strep Mutans cant respire.
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Hydrogen Sulfide Production Test
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Medium has cysteine, thosulfate, and ferrous sulfate as S reservior. If the bac has enzyme to convert S to H2S or uses thiosulfate as a terminal e- acceptor to get H2S, a black precipitate emerges.
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Nitrate Reductase Test
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If nitrate can be used as a terminal e- acceptor, then it will be reduced to nitrite and react to make solution red. +=Anaerobic respiration
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Oxidation/fermentation (O/F)
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Agar separated into oxic (top) and anoxic (bottom) zones. Growth up top = aerobic respiration, growth on bottom = fermenter, both = facultative
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Catalase test
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Superoxide -> via superoxide dismutase-> H2O2; ->via catalase-> H2O and O2. If catalase is present, forms bubbles when added to colony. Some have catalase but don't respire.
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What are all the sources of NH3 for bacteria?
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Nitrate via nitrate reductase, arginine via arginine dehydrogenase, urea via urease, tryptophan via tryptophanase and N2 via nitrogen fixation. The first for work in humans. "AUNT"
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Urease Test
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If the organism has urease for urea utilization, the liquid turns hot pink as the pH goes up. Urea -> NH3
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Indole test
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Tryptophan -> NH3 + indole + pyruvate If tryptophan is utilized, the indole resulting reacts to produce a red color. Trp is source of NH3
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Arginine dehydrogenase (ADH)
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Arg -> via Arg Dehydrogenase (ADH) -> ornithine + NH3 + CO2
This reaction results in inc. in pH to red/orange color |
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Lysine decarboxylase (LDC) test
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lysine -> via LDC -> cadaverine; this inc. the pH and change color to orange/red
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Ornithine Decarboxylase (ODC) test
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Ornithine -> via ODC -> putrescine; inc pH and yellow to orange/red
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What is a siderophore?
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Product of some bacteria that can steal Fe from the heme of a host. Fe contained in protein, Ferritin, and Transferrin
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What are the three types of hemolysis performed by bacteria?
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gamma hemolysis - non-hemolytic
alpha hemolysis - partial hemolysis, green discolorization beta hemolysis - complete hemolysis, clear zones around colonies |
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What is the purpose of bacterial Tween 10?
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It makes lipids from blood cells more accessible by solublizing them for utilization for energy. The FA's undergo beta oxidation. Found in bacteria performing hemolysis.
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Trimethoprim and Sulfonamides
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Blocks the synthesis of tetrahydrofolic acid to make DNA, RNA, tRNA and proteins. Most bacteria can't uptake it and must sythesize it.
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Rifampicin
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Binds the RNA pol - DNA complex while sigma is still attached and inhibits transcription initiation.
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Metronidazole
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Induces breaks in the DNA
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Aminoglycosides
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bind 16S rRNA & A site of 30S ribosome subunit to inhibit formation of the initiation complex, work on oxidative bacteria & req. proton motive force to cross the membrane
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Oxazolidinones - Zyfox (linezolid)
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Ab that prevents formation of f-met:mRNA:30S subunit ternary complex; active against MRSA, VRE and multiresistant S. pneumoniae
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Tetracycline
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interacts with 16S rRNA and 30S ribosomal subunit, weakens codon-anticodon interactions
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Lincosamides
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bind 50S subunit & inhibits peptide bond formation (inhibits linking of peptides)
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Macrolides (Erythromycin)
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binds 50S causing release of the peptide chain, so Macro it pushes it off
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Streptogramins
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bind 50S subunit and block translocation of the peptide chain to the E (P) site.
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What are the functions of the five types of bacterial protein secretion complexes?
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type I: Ab efflux pump for resistance
typeII: general prot. secretion typeIII: toxins, direct secretion into euk cells type IV and V: pili, toxins, DNA; indirect injection |
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What protein secretion complexes do Gm- bacteria have?
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They have them all, however I, III, and V are specific to Gm- bacteria. IV and II are had by Gm+ also.
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How are most pathogens classified by pH, salt tolerance, and temperature tolerance?
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Most pathogens are neutrophiles, non-halophiles or halotolerant, and mesophiles
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Fastidious organism
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have special growth conditions and nutrient requirements
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In what ways can bacteria within a biofilm differentiate physiologically?
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1.UV light sensitivity
2. Increased genetic exchange 3. biodegradation 4. secondary metbolite secretion: acid 5. exceptionally resistant to Ab |
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T/F Pathogen colonization always manifests itself in the host through disease.
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False, colonization can be intermittent or season, and so can virulence of the pathogen go into dormancy.
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What are some of the harmless primary colonizers of the oral cavity?
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S. gordonii, S. oralis, S. mitis : they bind the pellicle via adhesins
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Coaggregation
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interaction between cells in a suspension
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Coadhesion
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interactions with clups of cells in a suspension or bioflim
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What are the three layers of fermentors found in oral bacteria from nearest the tooth to furthest?
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Carbohydrate fermentors, Latic acid fermentors, and amino acid fermentors
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What are two common spore-forming bacteria?
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Bacillis anthracis and clostridium
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What is MBC and MIC?
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MBC - minimum bacteriocidal concentration
MIC - minimum inhibitory concentration |
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What is the Kirby-Bauer test?
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A way of determining Ab resistance of bacteria.
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What is the difference between an intermediate resistant organism and a fully sensitive organism?
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The former requires more than 1/2 of the clinically achieveable dose of Ab to have an effect, while the later requires less than 1/2 of the clinically achieveable dose.
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What is the difference between mutational resistance to Ab and acquired resistance?
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Acquired resistance came by way of mobile elements such as transposons and plasmid, while mutational arises by clonal spread of mutated bacteria.
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What do type I secretion complexes do?
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They are efflux pumps that help resist Ab by pumping them back out of the cell. Single strains of bacteria can accumulate multiple efflux pumps = resistance to mult. Ab.
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beta-lactamases
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Confers resistance to beta-lactams (ie penicillin) by cleave and inactivation.
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What is the function of beta-lactamase inhibitors?
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They soak up beta-lactamases and get them out of the way so that beta-lactams can work on bacteria, often administered in conjunction with beta-lactams
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How did ESBL's arise?
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Extended spectrum beta-lactamases arose because drugs were used that weren't recognized by conventional beta-lactamases, which spurred the evolution of ESBL's
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Fosfomycinases
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Bacterial defense which cleaves fosfomycin, which is an Ab that inhibits peptidoglycan layer growth by blocking conversion of NAG to NAM.
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Acetyl transferase
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Bacterial defense that inactivates chloramphenicol/aminoglycosides, which is an antibody that blocks the formation of the initiation complex in translation.
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MRSA
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methicillin resistant Staphylococcus aureus - methicillin is a modified beta-lactam, these S.aureus encode new PBP that the Ab can't bind.
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beta-lactam resistant Strep pneumonia
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PBP2X - low level resistance to penicillins
PBP2b - low and high level resistance to cephalosporins |
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MLS
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23S rRNA in 50S is methylated to prevent interaction with erythromycin and inhibits lincosamides/clindamycin family and streptograminB fam
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Target site modification - example for transcription
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changes in RNA polymerase structure prevents rifampicins from interacting.
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What is the mechanism for Vancomycin resistance?
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Vancomycin binds D-ala D-ala in cell wall and stop transglycosylation and transpeptidation. Modification of genes changes site to D-ala D-lac
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Trimethoprim
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Targets dihydrofolate reductase, a mutant enzyme is resistant.
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What do bacteria lack that eukaryotes have?
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Nuclear membrane and mitochondria
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Why is continuity important in the administration of Ab?
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Because of phenotypic lag, a gene could be mutated, but the mutation may take some type until it expressed phenotypically. If the patients relapse becuase of discontinuity in Ab usage, then they are more likely to exhibit resistance to the Ab. Want to kill it during the lag.
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Transition
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Base substitution involving a purine and a purine or a pyrimidine and another pyrimidine
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Transversion
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Purine for pyrimidine
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5-BromoUracil
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A base analog that usually pairs with adenine but causes errors in replication.
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Intercalating agent
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Stick themselves between base pairs of the DNA and cause frame-shift mutations. Ex. Ethidium bromide, Acridine orange, Acriflavine
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Pyrimidine Dimer
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Cause by UV irradiation which causes inaccurate repair mechanisms.
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Suppresor mutation
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Intergenic suppressor - ex. a base change after a mutation that restores the triplets to original coding. Extragenic suppressor - ex. a outside genes whose effects supress a mutation.
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Ames test
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Uses salmonella typhimurium, a bug doesn't need histidine. Mutated His- strains can be found and tested for reversion or suppresor mutations that will allow them to grow.
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Transformation
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A competent recipient uptakes chromosomal free floating DNA from a donor and recombines it into its genotype.
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Transduction
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A donor is infected by a Bacteriophage, the cell builds new phages from acquired DNA and has donor DNA it it. Recipient receives injection from phage and recombines its DNA.
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Conjugation
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A donor contacts a recipient with a sex pilus, donor DNA is transferred and recipient recombines and DNA is incorporated.
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RecA
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Involved in carrying out homologous recombination.
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Lytic vs Lysogenic
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The Phage DNA is incoporated and immediately causes building of other bacteriophages that eventually cause the cell to burst (clear plaques), where in the lysogenic phase the integrated DNA is inactive (turbid plaques).
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Lambda Repressor C1
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When integrated it promotes lysogeny and represses the lytic phase. Keeps phage quiescent, emerges from quiescence when excised, gal or bio can be added to ends if excision is off center.
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Conjugation from an F+ plasmid to an F- results in:
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Two F+ plasmids
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Why are plasmid able to replicate separately from the chromosome?
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Because they have an origen of replication. F plasmid has OriT
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Why is the F plasmid able to integrate itself into the chromosome?
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Because at about 25 different sites the plasmid and the chromosome have short homologous sequences.
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What is an adhesin?
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Involved in conjugation of a Gm+ bacteria, which is released upon stimulation by the donor cell and causes the donor and recipient cells to clump together to allow transfer via cell-to-cell contact.
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Replicon
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Replicate separately from the host chromosome and are partitioned into both daughter cells at the time of replication.
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What is the mechanism of plasmid resistance for Penicillins and cephalosporins
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This Ab targets the cell wall, so they encode for beta-lactamase to hydrolyze the Ab.
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What is the mechanism of plasmid resistance for Erythromycin and Clindamycin?
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The 23S portion of the 50S RNA subunit is modified by a methylase to inhibit interference of Antibiotics.
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What is the mechanism for Tetracycline resistance?
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Tetracycline interferes with the ribosome 30S subunit (weakens the codon-anticodon interaction) so inducible membrane proteins pump out the Ab.
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What is the mechanism for Sulfonamides resistance?
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Sulfonamides inhibit the enzyme dihydropteroate synthetase which is part of folate synthesis, so, the organism makes a resistant enzyme.
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Trimethoprim, what is the mechanism for antibiotic resistance?
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Trimethoprim inhibits the enzyme dihydrofolate reductase which is part of folate synthesis, so the organism makes a resistant enzyme.
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Streptomycin, what is the mechanism for resistance?
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Streptomycin interferes with the ribosome, so the cell modifies the gene and the resulting ribosome can't be interfered with by streptomycin
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Vancomycin, what is the mechanism for resistance?
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It interferes with cell wall synthesis so new enzymes are made to make the peptide side chain D-ala D-lac instead of two D-ala so it cant bind.
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What bacterial strain does pXO1 belong to and what does it encode for?
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Bacillus anthracis; it codes for lethal factor, protective factor and edema factor. LF + PA = lethal toxin: protease, attacks MAPKK2 and PAPKK1, kills macrophage. EF + PA = edema toxin: adenylate cyclase
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What bacterial strain does pXO2 belong to and what does it encode for?
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Bacillus anthracis; it encodes for a polyglutamate capsule which helps avoid immune system and inhibits phagocytosis.
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Promiscuity
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A concept dealing with how well a plasmid can move between species?
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Incompatibility
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Refers the the ability or inability of two plasmids to coexist stably in the same bacterial cell.
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What is the quickest way to screen for plasmids?
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Agarose gel electrophoresis
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Explain what a transposon is.
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Pieces of DNA that can move (transpose) as discrete units from one site in a replicon to another in the same replicon or into another replicon. The replicon may be in the plasmid or the chromosome. Transposons aren't replicons
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Where do translocatable drug resistance elements reside?
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Within transposons
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What are insertion sequences?
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The smallest transposons that code for their own transposition. They inactivate a gene by inserting themselves into it. Organism looses that phenotype.
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What is Tn10
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A composite transposon which is two transposons teamed up an have an overt phenotypes. Two IS10, IS10L and IS10R, flanking a gene for tetracycline resistance. R codes for transposase.
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What is a conjugative transposon?
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It induces bacteria to conjugate (integrate into a chromosome) w/o any plasmid. Can do "plasmid free" transfer of drug resistance. Referred to as Integrative and Conjugative Elements (ICEs)
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What is MRSA?
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Methicillin Resistant Staph aureus, has gene mecA which contains IS elements, transposons and integrated plasmids. Give resistance to many Ab, methicillin bc it changes PBP.
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What is SCCmec?
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Large MRSA genetic elements called Staphylococcal cassette chromosomes. Mostly assoc. with hospital infections but also found in community.
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What is the cag?
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cytotoxin associated antigen protein is a pathogenicity island (PAI) that is found in Helicobacter pylori which causes gastritis and peptic ulcers. The disease is more overt when cag is present.
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What is transposition?
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Site-specific recombination that doesn't require homology and is specific for the ends of transposons.
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(T/F) A holoenzyme is the RNA pol w/o the sigma factor?
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False, the core unit is without the sigma factor, the holoenzyme includes it.
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Why are some promoters better attractors of RNA pol than others?
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They are more similar to the consensus sequence and therefore have less of a need for an activator to help bind RNA pol.
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Core enzyme is specific for certain promoters. (t/f)
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False, sigma factor confers specificity
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How does Rho-dependent termination differ from Rho-independent termination?
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Rho terminates transcription in the former, but inverted repeats in the RNA which form a hairpin, followed by U's causes termination.
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What do lacZ,Y,A code for?
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Z - beta galactosidase
Y - permease (catalyzes uptake of beta galactosides A - transacetylase - role unclear |
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What does lacI code for?
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The repressor, which is an allosteric protein and has affinity for Beta-galactosides and the operator.
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Explain why the lac operon is an inducible system.
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Because the repressor normally hinders the transcription of the lac operon unless beta-galactoside (an inducer) is bound which causes it to loose its affinity for the operator.
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What is the difference between a trans-acting factor and a cis element?
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The lacI gene is a trans-acting factor because is doesn't need to be near the lacO to have its affects on it, the repressor when produced can diffuse in and bind it. However, the lac O is a cis elemnt because it controls genes, the lac operon, that are immediately adjacent to the chromosome.
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What does negative control refer to with regards to the lac operon?
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The repressor-operator system is one of negative control, because the repressor keeps it off unless stimulated otherwise. You only want to use lactose when its present.
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How is the Trp operon controlled?
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Its controlled by a repressor-operator system in which the repressor doesn't naturally have affinity for and bind to the trp operator unless tryptophan (the inducer) is present. The trp operon codes for enzymes of trp biosynthesis. You only want to make trp when its absent
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What does it mean to say that the ara operon is under positive control?
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The ara operon is naturally turned off, however, it has a trans-acting factor (an activator) that turns on transcription of the ara operon when it is bound by arabinose (the inducer).
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How can you tell positive control from negative control?
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Delete the regulatory gene, if you get constitutive expression then you've knocked out a repressor involved in neg. control, but if you get no expression, then you've knocked out an activator involved in positive control.
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What is the SOS response?
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It is an example of global regulation. LexA repressor that inactivates many DNA repair genes. In SOS, DNA damage activates RecA which causes the proteolysis of LexA so the DNA can be fixed.
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(T/F) Sigma factors can be considered as global regulators because they can direct the expression of a whole system of genes.
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True
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What is a two-component signal transduction system?
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Has two protein components, a histidine kinase and a response regulator or effector. The histidine kinase auto-activates/auto-phosphorylates in response to the environment, and then activates by phosphorylating the aspartyl residue of the response regulator. Found in higher eukaryotes. Targets for new Ab.
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(T/F) All multicellular organisms have some form of an adaptive immune response.
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False, only vertebrates have an adaptive immune response as well as an innate immune response.
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How long does it take for the body to make Ag-specific Ab?
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7 days before the adaptive immune response kick in, the innate immune response works in the mean time.
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What are spleen macrophages called?
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Sinusoidal macrophages
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What are macrophages in the brain called?
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Microglia
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What are macrophages called in the blood?
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Monocytes, precursors to macrophages.
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Which cells characterize acute infections?
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Presence of PMNs
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Which cells characterize chronic infections?
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macrophages
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What are some of the receptors on macrophages that facilitate phagocytosis?
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CR3 (binds to the opsonin C3b), mannose receptors, toll-like receptors and CD14 (recog. LPS)
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What types of enzymes are contained within lysosomal granules?
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elastase, esterase, lipase, ribonucleases, proteases, collagenase, lysozyme, etc
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What are the metabolic consequences of Phagocytosis?
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-Increase in glycolysis by the hexose monophosphate shunt
-Increase in uptake of molecular oxygen -Increase in production of peroxide. |
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How is superoxide formed?
|
Oxygen is given a single electron from NADPH (which comes from the HMP shunt) via NADPH oxidase.
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How is Hydrogen peroxide formed?
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via superoxide dismutase
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What is the function of myeloperoxidase (MPO)?
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Converts hydrogen peroxide to hypochlorous acid (bleach). Found mostly in PMNs
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What is Chronic Granulomatous Disease of Childhood (CGD)?
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X-linked killing defect of PMNs. Patients lack NADPH oxidase activity, so they can't make superoxide from O2 and NADPH.
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Why are patients w/ CGD effective against bugs that make peroxide, but not against those that make it and also have catalase?
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They can use the peroxide from the bugs to make Hypochlorous acid with their MPO, but not if the bug has a catalase to neutralize it to water and oxygen.
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How do macrophages utilize NO?
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They produce it bc it is microbiocidal. Arg + O2 ->via NO synthase-> citrulline + NO. NO can also combine with superoxide to make the microbiocidal peroxynitrite.
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What are cationic proteins?
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large molecular weight proteins in lysosomes of PMNs that punch wholes in membranes of Gm+ bacteria.
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What are defensins?
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Small molecular weight proteins that have antibiotic properties, found mostly in PMNs
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What is a lysozyme?
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Found mostly in PMNs, an enzyme that breaks down microbial peptidoglycan layers.
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What are NK cells?
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Don't have Ag-specific receptors. Release granules on non-self targets (without MHC I). Can activate Mphages to make NO.
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What do dendritic cells present Ag's to?
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T-cells for initiation of the adaptive immune response. They are a bridge between innate and adaptive immunity? Macrophages can do this too, but these are pros.
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What factors facilitate rolling?
|
Selectins on both Neutrophils and endothelial cells weakly bind glycoproteins on both cells.
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What surface modifications facilitate margination.
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Integrins on neutrophils bind ICAMs on endothelial cells.
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What is c-reactive protein (CRP)
|
Its an APRP (acute phase response protein) that binds polysaccharides on pneumococci
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What is mannose binding lectin?
|
APRP (acute phase response protein) that binds mannose motifs on bacteria and triggers complement activation via the lectin pathway
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What is LBP?
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Lipopolysaccharide Binding Protein is an APRP(acute phase response protein) that binds LPS and helps it bind to the CD14 (a pattern recognition receptor) on Mphages to elicit an immune response.
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What does N-formyl methionine receptor bind?
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It binds a 3 aa. molecule (f-met-leu-phe) made by bacteria and allows for chemotaxis of phagocytes with these receptors.
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What is CD14?
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Receptor on monocytes/Mphages that binds LPS
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What is a PAMP?
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Pathogen Associated Molecular Patterns, have low specificity but broad reactivity
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What are Toll-like Receptors?
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TLRs are also called PRRs (pattern recognition receptors, and recognize PAMPs (pathogen associated molecular pattern)
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TLR2 and TLR6
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Recognize products of Gm+ bacteria and fungal cell wall products.
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TLR4
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Recognize LPS
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TLR5
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Recognize flagellin
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TLR3, 7, 8, and 9
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React with microbial RNA or DNA or synthetic ligands
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NLRs
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NOD-like receptors are in the cytosol of Mphages and respond to invasion of the cell by the microbes, have leucine-rich repeats.
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IL-1
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Released by Mphages when they ingest microbes; endogenous pyrogen; Causes hypothalamus to cause fever which kills bacteria.
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IL-6
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Mediates the release of acute phase response proteins (APRP) from the liver including C-reactive protein
From Mphages |
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IL-12
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causes release of IFN-gamma which activates Mphages to increase capacity to make reactive oxygen intermediates for synth of NO. From Mphages
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TNF-alpha and IL-1 together do what?
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From Mphages; induce increased expression of adhesion molecules on endothelial cells and increased prod. of chemokine, IL-8 from Mphages = increased margination
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IL-8
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From macrophages, chemotactic for neutrophils
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What is the result of too many pro-inflammatory cytokines?
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Sepsis syndrome that can ultimately result in multi-organ dysfunction and death. TLR4 can do this
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What is the model for releasing pro-inflammatory cytokines to mediate the host defense to pathogens?
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Mphages -> IL-12 -> NK cells -> IFN-gamma -> Mphage activation = macrophages make more NO, H2O2, HClO, NO3
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How do epitopes that T-cells can recognize differ from epitopes that B-cells can recognize?
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B-cell epitopes may be linear or conformational (found on outside of proteins); therefore, the proteins don't have to be degraded before recognition. T-cell epitopes are always linear, but can recognize epitopes on inside of protein bc they are degraded.
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What does it mean when an Ag is T-cell dependant?
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It means that the Ag must be recognized by both B and T-cells for an optimum Ab response. The Ag must be degradable and presentable by an APC in order to be T-cell recognizable. Most Ag's are T-cell dependant.
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T/F Bigger Ag = better immunogens
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True, most have weights of 10000 or greater.
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What is the nature of T-independent Ag?
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Trigger limited immune response w/o activating T-cells. Usually less complex w/ repeating epitopes. Cross-link Ag to B-cells.
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What is a hapten?
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Ag, not an immunogen. Can stimulate an immune response if conjugated to a larger molecule.
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What are Ig's chemically?
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Glycoproteins
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Which side of the Ab is the N terminus?
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The Fab portion, this parts on the Ab closest to this end are the hypervariable regions.
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Which side of the Ab is the C terminus?
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The Fc portion
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Which part of the Ab determines the class of Ab?
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The heavy chain.
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What are the two classes of light chain?
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Lambda or Kappa, but they must be the same on on a single Ab.
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IgM
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First Ig made by the fetus and following an antigenic stimulus. It fixes complement. Its a pentamer, and monomers are bound by disulfide bonds.
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IgG
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Predominant Ig in the blood, fixes complement, crosses the placenta and has a longer half-life. Can provide fetus w/ protection.
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IgA
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Secretory (some), dimer; predominant Ig in secretions, secretory component protects against proteolytic degradation, presence in colostrum and breast milk provides protection to nursing infants.
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IgE
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Binds to mast cells and basophils by Fc, involved in Type I hypersensitivity, believed to play a role in protection against some parasites.
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IgD
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Only known role is as receptor on B-cells
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Isotypes
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Antigenic determinants present in all members of a species, but can't be given to other species.
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Allotypes
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Antigenic determinants which vary between members of a species, so can't be given to other members of a species.
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Idiotypes
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Antigenic determinants existing in the variable regions of the Ab molecules. Within an individual, make an immune response against your own Ab.
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What determines if Abs are polyclonal?
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If they recognize many different epitopes.
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What is humanization?
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Humanized mouse monoclonal Abs are generated by cloning mouse variable regions genes and human constant region genes into cells which subsequently produce chimeric Ab molecules with reduced antigenicity and enhanced biologic fxn in the human system.
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What chromosomes are the heavy and light chains on?
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Heavy = 14
Kappa = 2 Lambda = 22 |
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What are the variable segments of a light chain gene?
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V = a 5' variable segment
J = a joining segment C = constant segment |
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What are the variable segments of a heavy chain?
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V = a 5' variable segment
D = diversity segment J = a joining segment C = constant segment |
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What is affinity maturation?
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Occurs following Ag activation of a B-cell and high rates of somatic mutation of V genes occurs. The mutant with greatest affinity for Ag are preferentially activated and proliferated.
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What are the 5 mechanism contributing to Ab diversity?
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1. Multiple copies of VDJ gene segment
2. Junctional diversity - recombination 3. Insertion of N (nontemplated) nucleotides (heavy chain) 4. Combinatorial diversity (heavy chain and light chain pairing) 5. Somatic mutation (driven by Ag) |
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Where are the membrane forms of IgM and IgD found, and when do they become the secretory form?
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On the surface of B-cells, when B-cells activate and differentiate to plamsa cells, the Igs are secreted.
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What is class switching?
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Switch sites are found 5' to all C region gene segments except IgD. Recombination between switch regions is responsible for the expression of other Ig classes. (looping out) Its Ag driven and cytokine mediated
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What are prothymocytes?
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Progenitor T-cell before they mature in the thymus.
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How do lymph nodes stimulate the immune system?
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Lymph and blood cross paths, lymph provides Ag, and blood brings t-cells in the paracortex and b-cells in the peripheral cortex. Lymph is brought here before entering the bloodstream.
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How does the spleen stimulate the immune system?
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Arteries entering the spleen are surrounded by white pulp of T-cells and dendritic cells. The adjacent marginal zone contains B- cells. These all respond to blood-borne pathogens.
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MALT
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Lymphoid tissue in gut and respiratory system just under mucus membrane and cont. T-cells and B-cells (in germinal centers) GALT has IgA bearing B-cells as opposed to IgG and IgM in the spleen and lymph nodes.
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Cutaneous-associated lymphoid tissue
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Work under the skin, langerhans cells (dendritic cell) and intraepidermal lymphocytes (primarily T-cells)
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What is the role of Th1 cells?
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Using cytokines to stimulate Macrophages
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What is the role of Th2 cells?
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Use cytokines to stimulate the differentiation of B-cells and Ig class switching.
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CD8
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On cytotoxic T cells
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CD4
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On T helper cells
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TCR
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t cell receptor gene segment and can undergo class switching.
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B-cells
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Differnetiate into Ab factories once stimulated. Can also serve as APCs in secondary immune response.
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Mast Cells and Basophils
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Have granules with vasoactive amines. High affinity for Fc of IgE - type 1 hypersensitivity and and parasites.
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How do cytokines exert their effects?
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In a autocrine or paracrine fashion, by communicated with cells with receptors and upregulating the number of receptors on that cell. They work through innate and acquired immunity.
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