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422 Cards in this Set
- Front
- Back
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Chapter 3
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Chapter 3
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3 challenges of free living unicellular organisms
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nutrition, occupancy, resistance
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gram positive cell wall
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thick, contains murein/peptidoglycan
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components of murein
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sugar and amino acid polymer
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function of rigidity of murein coat
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allows organism to survive in hypoosmotic media
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lysozyme
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murein hydrolytic enzyme found in human and animal tissues, causes bacteria to lyse in low osmotic pressure environments or to become spheroplasts in iso-osmotic media
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gram stain procedure
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1. stain with crystal violet 2. modify with potassium iodide 3. wash with alcohol, only gram positive will remain purple. 4. counterstain with safranin which causes gram negatives to become pink
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acid fast stain procedure
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1. stain with hot carbol fuchsin (red) 2. decolarize with acid alcohol, only acid fast remain red 3. counterstain with methylene blue
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describe the structure of murein
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alternating units of N-acetylmuramic acid and N-acetylglucosamine with crosslinking peptides resulting in a fence like structure
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3 components of LPS
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lipid A, core, and O antigen
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Lipid A
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anchors LPS in outer leaflet of gram negative membrane
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components of LPS core
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short series of sugars (ketodeoxyoctanoic acid and a heptose)
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O antigen
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long carbohydrate chain that covers bacteria and protects it from hydrophobic compounds
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how are hydrophilllic compounds transported through gram negative cell wall
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via porins
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periplasm
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space between the double plasma membranes in gram negative organisms
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contents of periplasm
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gel like solution containing murein and various enzymes to reduce large molecules to diestible size and protect against bacteriophages and antibiotics
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effect of lipid A on body
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also known as endotoxin, results in fever and mobilization of host defense, if present in high enough amounts can cause shock
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explain the advantages of acid fast solution
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relatively impervious to envionmental agents but growth is very slow because the waxy membrane makes for slow uptake of nutrients
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antibiotic classes that block synthesis of murein
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beta lactams (penicillin, cephlosporins, carbapenems)
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describe the synthesis of murein
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chain of sugars alternating between N-acetylglucosamine and N-acetylmuramic acid (which has a peptide chain attached to it). The units are transferred from cytoplasm to periplasm by a lipid carrier
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MOA of vancomycin
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prevention of the addition of disaccride (NAM-NAG) to growing chain of murein
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inhibits regeneration of the lipid carrier for murein
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bacitracin
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final reaction of murein synthesis
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transpeptidation to link the long chains of disacchrides (cross linking)
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what forms the cross link in murein
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the subterminal D-alanine of one chain joining with a lysine or diaminopimelic acid on the other chain
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what antibiotics inhibit the cross linking reaction
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penacillins and cephalosporins
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how do antibiotics that inhibit murein synthesis kill bacteria
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via lysis, caused by disruption in murein synthesis. This disruption results in overgrowth of the cytoplasm
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autolysin and penicillin tolerance
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bacteria tolerant to penicillin are deficient in an autolysin which cleaves murein,
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facilitate the entry of most metabolites into bacteria
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permeases
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group translocation
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phosphorylation linked transport used to bring in certain sugars such as glucose, resulting in the transported substance being chemicaly altered in the process
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proton motive force
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protons expelled from bacteria during oxidation of metabolites creates a gradient that can be utilized to bring in energetically unfavorable molecules such as lactose via symport
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how do organisms within the body take up iron
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excretion of chelating compounds called siderophores which bind free iron and can be specifically be taken up by the organism
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nucleoid
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irregular coiled DNA structure found in bacteria
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DNA gyrase
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introduces supercoils into circular DNA
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topoisomerase 1
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relaxes supercoils by introducing single strand nicks in the DNA
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brief description of bacterial DNA replication
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bidirectionally at a precice replicative origin that requires precice unwining and rotation of supercoiled nucleoid
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metronidazole is active in what form
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partially reduced
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what organisms are metronidazole most effective in, why
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anaerobes and amoebas, they partially reduce the molecule which is the active form
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MOA of metronidazole
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partially reduced form incorporates into DNA of bacteria and causes it to become unstable
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nalidixic acid
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inhibits DNA gyrase
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MOA of fluoroquinolones
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interfere with DNA gyrase and topoisomerase to cause dsDNA breaks
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antibiotic that inhibits bacterial transcription at initiation step
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rifampin
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principal biosynthetic activity of rapidly growing bacteria
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protein synthesis
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RNA is made in bacteria at a rate proportional to _________________
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number of RNA polymerase molecules
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protein synthesis in bacteria occurs at rate proportional to _____________ ; what does this tell us
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number of ribosomes, that regulation occurs with initiation of protein synthesis and not the actual speed of chain elongation
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MOA of macrolides
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block formation of peptide bonds by binding near.at the tRNA binding site on the 50s subunits, this prevents chain elongation
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are macrolides bacteriostatic or bacteriocial, why?
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bacteriostatic, eventually the effected portions of the ribosome are hydrolyzed and the remaining subunits are able to join another mRNA molecule
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what type of patient would not respond well to macrolides, why
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immunocomprimised patients cant clear bacteria effectively, meaning the macrolides would halt the growth but the immune system wouldn’t finish the job
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bactericidal protein synthesis inhibitor antibiotic class
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aminoglycosides (the -mycins)
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where do aminoglycosides bind
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to the smaller 30s unit
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MOA of aminoglycosides
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bind to 30s subunit and cause increased 30/50s interaction leading to accuulation of 70s particles, it also prevents elongation of peptide chains. The aminoglycoside molecules cannot be removed from the bacteria and result in death of the molecule
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slimy outer coating made by certain bacteria |
capsule |
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2 types of filaments that protrude through surface of bacteria
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flagella and pili
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another name for pili
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fimbrae
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explain the mechanics of the 2 forms of bacterial motion
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chemotaxis involves bacteria being attracted or repelled by substances in ins environment. If bacteria are attracted the flagella will beat counterclockwise which results in straight line movement, if repelled they rotate clockwise which results in random tumbling, while often impersise there is a net movement toward attractants and away from repellants
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MOA of imidazoles
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block synthesis of ergosterol required for fungal cell wall integrity (-azole drugs)
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MOA of echinocandins
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block beta glucan synthesis, a component of fungal cell walls
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lipopeptide antibiotics MOA
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form channels in cell membranes of G+ bacteria
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MOA of polyene: amphotericin B
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bind to sterols in eukaryotic cell membranes leading to lysis
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MOA of folate antagonists
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sulfonamides inhibit dihydropteroate synthesis . Trimethoprim inhibits DHF reductase
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antigenic variation
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capability in some bacteria to change amino acid composition of pili to evade immune detection/response
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phase variation
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some organisms such as salmonella undergo rapid changes between expression/non expression of genes that code for flagella proteins
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2 groups of nutritional requirements for bacteria
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photo/chemosynhetic bacteria that use light/chemical energy to subsist on CO2 and organisms that require organic compounds
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all pathogenic organisms have this nutritional requirement
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require organic compounds to survive
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strict aerobe
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requires oxygen to grow
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strict anaerobe
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cannot grow in presense of oxygen
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facultative anaerobe (include common example)
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can grow with or without oxygen, example: E Coli
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final electron acceptor for strict aerobes
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molecular oxygen, this is respiration
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final electron acceptor (give 2 examples) for anaerobes
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pyruvate (to form lactate) and acetyl coA to form ethanol. This is fermentation
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bacterial species that can grow on hundreds of organic compounds and are omnipresent in water/ soil
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pseudomonas
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2 bacterial species that can grow on many types of media
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pseudomonas and e coli
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minimal media
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contains a solution of glucose and several other minerals
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nutrient broth
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rich in nutrients and complex proteins that are required for some nutritionally fastidious organisms to grow
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nutritionally fastidious
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organisms that can only grow in complex media such as the human body, often these are highly parasitic organisms with nutritional needs near that or exceeding those of humans
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obligate intracellular parasites (3 examples)
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organisms that cannot be cultured in artificial media, include chlamydia, treponema pallidum (syphilis) and mycobacterium leprae (leprosy)
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generation time
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time it takes for a bacteria to become two
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total count
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count of the number of bacteria in a sample, counts as particles without discrimination between living and dead
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how do you determine the number of living bacteria
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via a colony count, which is done by applying a diluted sample to a solid medium then multipling the numbner of colonies that form by the dilution factor to determine the CFU or colony forming units originally present
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law of growth
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Nt = No x e^kt (where Nt is number at time t , No is initial number at time 0, k is the growth constant)
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stage of culture where growth stops
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stationary phase
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SOS response
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response of some bacteria to stresses such as E coli activating DNA repair genes when exposed to UV radiation
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sporulation |
some bacterial species produce spores which are exceptionally resistant to damage but are metabolically inert |
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metabolic parsimony
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bacteria tend not to make products that they cannot use at the time, this arises from the need for bacterial strains to be metabolicly efficient to survive
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operon
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multigenic segment of DNA found in prokaryotic cells that contain enzymes for a particular pathway, by stringing these genes together regulation can be controled by a single signal
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explain the regulatory steps and mechanisms of the b-galactosidase operon
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if lactose is only source of sugar, the bacteria requires b-galactosidase to convert it to glucose. The lactose allosterically inactivates the Lac repressor protein, releasing it from the operator sequence, allowing the RNA polymerase to progress with transcription of mRNA
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explain regulation of enzyme synthesis by attenuation
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using the example of leucine, a small bit of mRNA is produced from the beginning of the leucine operon, the RNA polymerase will reach the attenuator sequence, if leucine is present, the transcription stops as there is no need to synthesize leucine , if leucine is not present the operon is transcripted in full, so that the machinery to produce the needed amount
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Chapter 5
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Chapter 5
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3 substances/methods for nonselectively killing microorganisms
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heat, radiation, strong acids
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how do sulfonamides exert their antibiotic activity
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they compete with PAB (para aminobenzoic acid) which is a precursor to folic acid, without the ability to produce folate, bacteria cannot replicate
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why are our cells unaffected by sulfonamides while bacteria are
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we require preformed folic acid, sulfa drugs disrupt the production of folic acid not the utilization, fortunately bacteria cannot uptake and utilize the folic acid present in our bodies and must make it themselves, making them susceptable to sulfa drugs
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why are bacteriocidal drugs preferable to bacteriostatic
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organisms that remain alive can still harm host by producing toxins, or becoming drug resistant and resuming growth, however there are instances where bacteriostatic drugs are prefered
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explain how trimethoprim differs from sulfa drugs
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trimethoprim blocks the function of folic acid, by blocking DHFR, this is a required enzyme for humans as well as bacteria, but the concentration of TMP needed to block DHFR is substantially lower for bacteria/protozoa than humans (.005 mM vs 250 mM)
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how do beta lactam antibiotics expand their spectrum
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modification of B lactam ring and other parts to increase access to different bacteria, improve absorbtion, or counter bacterial resistance
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steps of beta lactam antibiotics
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1. associate with bacteria 2. (if G-) penetrate outer membrane and periplsm 3. interact with penacillin binding proteins on cytoplasmic membrane 4. activation of autolysin that breaks down cell wall murein
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beta-lactamase |
bacterial resistance enzymes that degrade penacillins, cephalosporins, and/or carbapenams |
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gram postive bacterial resistance to beta lactam drugs
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usually involves production and release of beta lactamases into surrounding media to prevent drug from reaching bacteria, if the antibiotic does reach the gram positive organism, it produces massive amounts of beta lactamase that cannot be overcome with higher doses of drug
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gram negative bacterial resistance to beta lactam drugs
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secreted constitutivey into periplasmic space
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can beta lactam resistance be overcome with higher concentrations of drug
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usually not in G+ but it is possible with gram negative because the amount of beta lactamases produced is constant
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other than beta lactamases, what are some other methods by which bacteria become resistant to beta lactam drugs
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gram negative organisms undergo porin mutatios which lead to exclusion of beta lactams from periplasmic space, PBPs can undergo mutations themselves, bacteria can become tolerant or lack autolysin
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MRSA |
methaicillin resistant Staph aureus, resistant to all penicillins and cephalosporins due to acquisition of an altered PBP (penacillin binding protein) |
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IV antibiotic commonly used for resistant Gram positive infections
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vancomycin
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explain how strains of enterococcus became resistant to vancomycin
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vancomycin targets the peptide chain of murein at its D-alanine -- D-alanine terminus, however VRE strains acquired a plasmid that altered the terminus to D-alanine -- D-lactate, which vancomyicin cannot act upon
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why is VRSA worse than VRE
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enterococci are considered less invasive and virulent than staph aureus
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how does daptomycin work?
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it is a lipopeptide antibiotic that is able to interfere with the gram positive cell membrane and form a destrictive ion channel
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what organisms are most commonly resistant to daptomycin
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VISA
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how do quinalone antibiotics work in gram + /- organisms
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act by inhibiting the topoisomerases DNA gyrase (+) and topo IV (-) resulting in strand breaks and loss of bacterial chromosomal integrity
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2 methods of resistrance to quinolone antibiotics
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mutation in genes coding for DNA gyrase and topo IV ; formation of quinolone efflux pumps in bacteria
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aminoglycoside MOA |
1. penetration of outer membrane of G- 2. associate with 2 stage active transport in cell membrane 3. bind to 30s ribosome to inhibit protein synthesis at or near initiation step |
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methods of bacterial resistance to aminoglycoside drugs
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most commonly, acquired plasmids code for genes that add modifiers to the aminoglycosides such as adenyl or phosphate groups rendering them inert. Less commonly bacteria can inactivate the transport of aminoglycosides
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major method of tetracycline resistance
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reduction of intercellular concentration by utilization of efflux pumps which remove the drug from the cell
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major method of macrolide resistance
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modification of the 50s ribosomal subunit. This is via methylation of the 23s ribosomal RNA. The modification confers macrolide resistance
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major method of resistance to oxazolidones |
similar to macrolide resistance, in that mutations to the 23s RNA of 50S ribosomal subunit block access of drug to ribosome |
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MOA of polyene antibiotics
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antifungal agents that target ergosterol in membranes of fungi
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MOA of imidazoles
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antifungal agents that target cyp P450 demethylase which is involved in sterol synthesis
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MOA of echinocandins
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inhibitors of B-glucan which is found in fungal cell walls
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synergism
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in combo therapy, 2 or more drugs have effects that augment each other
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antagonism (drug therapy)
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action of one drug reduces effectiveness of the other
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indifference (drug therapy)
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each drug works no better/worse than if it was administered alone
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read table 5-1
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then read it again, if you still don’t know it, read it a 3rd time
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Chapter 8
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Chapter 8
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adhesin that is found directly on cell surface and not on protrusions
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invasin
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integrin
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normal cellular receptor found on host cells that can be reconized by invading microbes
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fibronectin
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receptor for certain G+ bacteria that normally coats mucosal surfaces of epithelial cells
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bacterial adhesins of G- bacteria (3)
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pili, non fimbral surface proteins, capsules
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bacterial adhesins of G+ bacteria (2)
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surface proteins, capsules
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fibronetin deficiency increases risk of
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increased exposure to gram negative organisms
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scarcity of this nutrient limits potential for growth of bacteria in body
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free iron
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bacterial adaptations to free iron scarcity in body (3)
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secretion of high affinity iron chelators that can be taken up by the specific bacteria ; surface molecules that steal iron from IBPs of the host; bacterial hemolysis of red blood cells to acquire iron from hemoglobin
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why does brucella abortus cause spontaneous abortion in cattle but not other animals
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these animals have erythritol in their placentas, which B abortus has a high affinity for
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most effective way to protect against the antimicrobial action of compliment
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prevent its activation
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how do gram neg/+ organisms mask against compliment activation
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secretion of capsules to prevent compliment recognition of LPS (g-) or teichoic acids (g+)
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sialic acid
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sugar that inhibits compliment activation that is commonly incorporated into bacterial surface molecules
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describe the strategy that meningococci employ to avoid compliment activation (hint: wolf in sheep's clothing) |
become coated with circulating IgA which does NOT cause compliment activation. The IgA blocks access of other antibodies to the bacteria |
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how does HSV avoid detection from complement
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it has an envelope that binds C3b inhibiting activation by alternative pathway
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how does vaccinia virus avoid compliment activation
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it secretes a C4bp inds C4b and limits the extent of complement activation
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how does E coli hinder the success of the MAC
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smooth strains of E coli are able to avoid destruction by the MAC due to prolonged O antigen portion of LPS which limits access of the MAC to the organism surface. Rough mutants with little/no O antigen are readilly killed by the MAC
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O antigen and pathogenicity
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more O antigen correlates with higher pathogenicity , smooth = virulent , rough = not
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C5a peptidase
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secreted by group A streptococci, eliminates C5a which is a neutrophil chemotactic
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leukocidans
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exotoxins secreted by some pathogenic bacteria that kill neutrophils and macrophages
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NETS
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neutrophil extracellular traps, many bacteria can secrete nucleases that can destroy nets and enhanse survival
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protein A
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found on surface of staphlococci, streptococci and other bacteria, bind to wrong end of IgG molecule and stop them from acting as opsonins
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tuberculosis, psittascosis and legionnares disease survive within phagocytes how
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they inhibit lysosome fusion wih phagosome they are contained in
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how do listeriam shigellae, monocytogenes, and rickettsiae survive phagocytosis
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they escape the phagosome and enter the cytoplasm where they are safe from lysosomal enzymes
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listeriolysin
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required for escape of bacteria from phagosome, secreted by l monocytogenes
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how does the protozoa leishmania escape digestion in phagocytosis
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it is resistant to lysosomal enzymes
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how does legionella escape digestion in phagocytosis
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inhibition of hexose shunt and oxygen consumption to reduce power of respiratory burst
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syncytia and multinucleated giant cells
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result from viruses which spread by inducing fusion with other uninfected cells
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how can bacteria move through cytoplasm
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through the induction of polymerization of actin in the cytoskeleton. This can push the bacteria along the edges where it can escape the membrane into a neighboring cell
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superantigens
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toxins secreted by certain streptococci that stimulate a nonspecific T cell response resulting in diversion of immune resources and a toxic cascade of cytokines. They are able to do this because unlike regular antigens, they form a bridge between the APC and the T cell that is not variant, where as the bridge between APC and T cells in normal antigen binding occurs in a highly specific region
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what is the causative agent of sleeping sickness, how does it evade immune destruction
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trypanosoma brucei is a protozoan that causes sleeping sickness, it is covered with a thick variable surface glycoprotein that undergoes antigenic changes throughout infection, the antigens presented to the body on the surface are constantly changing, meaning the immune system is constantly playing catchup
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what is pilin and how do gonococci use them
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pilin is a protein that makes up pili which attaches to potential host cells, gonococci have pilin that changes and allows for multiple reinfections, as the strand that causes one infection is likely to be antigenically different than one that causes a recurrent infection
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antigenic drift/shift
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occurs in viruses such as influenza at the population level. A drift occurs about every 2-3 years and a shift occurs every 10 years or so.
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hemaglutinin, neuraminidase
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responsible for antigenic shift/drift in influenza virus, hemagglutinin serves to bind to cell surface receptors, neuraminidase changes these receptors
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staphytlokinase
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cleaves host plasminogen into plasmin at bacterial cell surface of staphylococci, this derades IgG and C3b preventing opsonization
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fabulation
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occurs when an organism cleaves IgA and remains bound to the inactive fragment (Fab) this prevents binding of intact antibody molecules
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Chapter 9
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Chapter 9
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3 methods of cell lysis during microbial infection
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1. production of toxin that affects cell membrane integrity 2. organism multiplies within the cell causing lysis. 3. microorganism is targeted and lysed by NK cells or cytotoxic lymphocytes
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general definition of toxin
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proteins that alter the normal metabolism of host cells, with deleterious effects on host
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how are bacterial toxins categorized
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by site of action in host
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where do exotoxins, type 3 cytotoxins and type 4-7 cytotoxins modulate their effects
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intracellular targets
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where do endotoxin, superantigens, membrane-damaging toxins and exoenzymes act
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cell surface, exoenzymes modulate ECM
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type 1 secretion system
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autotransporter built into exotoxin
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type 2 secretion system
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transport apparatus within bacterial membrane
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how do exotoxins reach their target
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they are secreted by bacteria and circulate until they encounter receptors on surface of specific cells and become internalized into the target cell
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are toxins required for bacterial growth
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not directly but may be needed for survival and spread within host
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when are toxins released by bacteria
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some release them continuously, others only when bacteria are not growing, for example diptheria toxin is only made when the diptheria are iron starved, this toxin causes lysis of iron containing cells
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A and B domains
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protein configuration of many exotoxins, with the B domain "Binding" to the membrane" so the A domain can enter the cell and Attack
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organization of cholera toxin
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AB5
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organization of anthrax toxin
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2A + B (they interact at the host membrane)
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edema factor
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an adenylate cyclase seen in the anthrax toxin
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lethal factor
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a protease seen in an A domain of the anthrax toxin
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ADP ribosyltransferases
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seen in many bacterial toxins, these transfer ADP ribose from NAD to target proteins covalently
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organization of diptheria toxin
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AB
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EF-2
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elongation factor 2, target of diptheria toxin, this is required movement of ribosomes on mRNA
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how does diptheria toxin work
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it’s A domain a ADP ribosyltransferase that targets EF-2 , severely limiting a cells ability to produce proteins. This is because the A domain covalenty attaches an ADP-ribose to EF2, perminantly inactivating it and preventing progression of ribosomes along mRNA. A single A subunit of diptheria toxin is sufficient to kill a cell, due to its long activity
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primary target of cholera toxin
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small intestine epithelium
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in 1 sentence how does cholera toxin affect cell
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by irreversibley raising intracellular cAMP, resulting in mass movement of ions and water into intestinal lumen
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how does cholera toxin raise cAMP in the cell
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the A subunit is a ADP ribosyltransferase, it transfers the ADP-ribose to a G protein which is then activated, resulting in continual stimulation of Adenyl Cyclase and high intracellular cAMP levels
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pertussus toxin and heat liable enterotoxin of E coli work similarly to what toxin
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cholera toxin, namely they activate AC by ADP ribosylation of G proteins
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blocks muscle contraction yielding flaccid paralysis
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botulinum toxin
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produces irreversable muscle contraction yielding spastic paralysis
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tetanus toxin
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most potent protein toxin to humans
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botulinum toxin
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anaerobic spore forming bacteria of genus clostridium produce these toxins
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neurotoxins (botulinism toxin and tetanus toxin)
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structure of tetanus and botulinism toxins
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single proteins with an A and B domain
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how does the effect of the A domain in Tetanus and botulinsim toxin differ
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in tetanus, the toxin migrates up an axon into inhibitory neurons where they block release of inhibitory neurotransmitters (resulting in spastic paralysis. In botox the A domain migrates to the peripheral nerve ending, blocking release of stimulatory NT such as ACh (resulting in flacid paralysis)
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what type of protein is the A domain of tetanus toxin/botulinism toxin
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protease that cleaves proteins responsible for fusion of synaptic vesicles with plasma membrane
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|
how are type 3 cytotoxins introduced to a host cell
|
by contact depentant mechanism where bacterium directly contacts host cell
|
|
|
injectisome
|
type 3 secretion system (T3SS) used by pathogenic bacteria to deliver type III cytotoxins to host cells in a contact dependant matter
|
|
|
salmonella, shigella, pseudomonas, cholera, and plague bacilli deliver toxins this way
|
T3SS
|
|
|
type IV to VII cytotoxins
|
we don’t know much about it, so Im not bothering to learn much about it.
|
|
|
endotoxin
|
another name for the LPS of the outer membrane of G neg bacteria
|
|
|
what is misleading about the name endotoxin
|
it is not internalized, and only toxic at high concentrations
|
|
|
what is a pattern recognition receptor
|
highly conserved factors seen in bacteria that are recognized by our immune system (Toll like receptors) these include endotoxin (from G neg bacteria) lipoteichoic acid (from G + bacteria) and lipoglycans from mycobacteria
|
|
|
components of endotoxin
|
lipid A, sugar core, O antigen
|
|
|
biologically active portion of endotoxin
|
lipid A….duh….A=Active (just like in A/B domains of exotoxins)
|
|
|
result of small/ large amounts of endotoxin
|
small is alarm reaction, large is shock an intravascular coagulation
|
|
|
alarm reaction results in
|
the increase in cytokines triggered by endotoxin binding to TLRs results in fever, vasodilation, inflammation, and increased antibody synthesis
|
|
|
fever induced by endotoxin is caused by _________ being released from __________
|
IL1 and TNFa being releced from mononuclear phagocytes
|
|
|
how does endotoxin activate compliment, what does this cause
|
endotoxin triggers the alternative pathway, resulting in MAC production, phagocyte chemotaxis and opsonisation. The compliment also causes anaphylatoxins which result in inflammatory response
|
|
|
effect of endotoxin on macrophages
|
increases everything they do. They make more lysozymal enzymes, eat more, and secrete more hydrolases
|
|
|
waterhouse friderichsen syndrome
|
adrenal insufficency due to infarction seen in DIC leads to death, seen in some cases of severe meningococcal infection
|
|
|
3 ways endotoxin contributes to pro-coagulative state
|
1. activates factor XII (intrinsic factor) 2. causes platelet degranulation. 3. causes neutrophils to release fibrin stabilizing proteins
|
|
|
lecithinase
|
lipase toxin produced by clostridium perfringenes which causes gas gangrene.
|
|
|
hemolysins
|
another name for membrane damaging toxins, due to their ability to be identified in laboratory by lysing RBCs on blood agar
|
|
|
example of homogeneous pore former
|
alpha toxin of staphylococcus aureus. Forms pores with same number of molecules (similar to pores formed by MAC)
|
|
|
heterogenous pore forming toxins (example and mechanism)
|
form membrane damaging pores of various sizes, prototype is streptolysin O that binds to cholesterol in cell membrane destroying RBCs
|
|
|
hyaluronidase and DNAse are examples of ___________ that act as ____________
|
exoenzymes that act as spreading factors, the hyaluronidase breaks down ground substance of CT and DNAse thins pus made viscous by dead WBCs
|
|
|
how do streptococci eliminate fibrin barriers
|
by releasing streptokinase which activates plasminogen to remove fibrin clots
|
|
|
toxoid
|
chemically inactivated toxin
|
|
|
Chapter 10
|
Chapter 10
|
|
|
Big 4 typical bacteria
|
gram positive/gram negative rod/cocci
|
|
|
2 most medically relevant genera of Gram positive cocci
|
streptococcus and staphylococcus
|
|
|
how do streptococci grow
|
in strings of spherical cells like pearls
|
|
|
how are streptococci subdivided
|
by weather they produce changes when grown on blood agar
|
|
|
beta hemolytic streptococci
|
destroy red blood cells, clear area around colony
|
|
|
alpha hemolytic streptococci
|
affect red blood cells partially, result in green area around colony
|
|
|
do streptococci carry out respiration
|
no, only fermentation meaning streptococci are STRICT ANAEROBES
|
|
|
oxygen tolerant anaerobe
|
although they do not respire they can grow in presense of air many pathogenic streptococci are oxygen tolerant
|
|
|
main pathogens in streptococcus genus are the _______ strains
|
beta hemolytic
|
|
|
most important b-hemolytic streptococci strains
|
streptococcus pyogenes aka group A strep
|
|
|
major alpha hemolytic streptococcus species
|
streptococcus pneumoniae
|
|
|
2 main pathogenic species of staphylococcus
|
staphylococcus aureus and S. saprophyticus
|
|
|
how to distinguish S. aureus from other staphylococci
|
with coagulase test, because only S. aureus produces it
|
|
|
most likely organism to cause pus in wounds
|
staphylococci
|
|
|
often produce serious infections in deep tissues such as osteomyelitis and endocarditis
|
staphylococci
|
|
|
most significant genus and species (2) of gram negative cocci
|
neissera gonorrhoeae which causes gonorrea and meningococcus ( N. meningititis) which causes meningitis/septicemia
|
|
|
toxin common to all gram negative organisms
|
endotoxin (lipopolysaccride)
|
|
|
what is the classification of the organism that causes diphtheria
|
gram positive rod, Corynebacteriu diphtheriae
|
|
|
in human environment most common gram positive rods are
|
sopre forming
|
|
|
2 categories of common gram positive rods found in humans
|
aerobic bacillius (B. anthracis which causes anthrax) strict anaerobes (belong to clostridium genus)
|
|
|
medically important agents of clostridium (4)
|
C botulinum, C tetani, C perfringens, C difficile
|
|
|
how do members of the genus clostridium cause disease
|
through powerful exotoxins
|
|
|
causes gas gangrene
|
C perfringens
|
|
|
associated with antibiotic use, causes pseudomembranous colitis
|
C difficile
|
|
|
gram positive rod that causes serious infections in immunocomprimised infants/adults
|
listeria monocytogenes
|
|
|
major clinical grouping of gram negative rods
|
enteric
|
|
|
enteric bacteria can be further divided by what characteristic
|
ability to ferment lactose
|
|
|
major lactose fermenter among enteric bacteria, major lactose non fermenter(s) among enteric bacteria
|
lactose (+) = e coli lactose (-) = shigella and salmonella
|
|
|
name several families of enteric bacteria that lie outside the family of enterobacteriaceae
|
vibrio, pseudomonas, campylobacter, helicobacter
|
|
|
name some genuses that are included in the fastidious and small G(-) rod family (6)
|
Haemophilius (pneumonia/meningitis) Brucella (brucellosis) , francisella (tularemia) Bartonella (cat scratch fever) Legionella (legionaires disease)
|
|
|
__________ are the most noteworthy strictly anaerobic gram negative rods
|
bacteroides
|
|
|
name some places that bacteriodes are found and some of their uses to us
|
they can break down some polysaccrides found in our bodies and serve as a stimulus for proper tissue development, usually these bacteria are harmless unless deposited in deep tissues
|
|
|
most common acid-fast bacteria
|
mycobacterium which include tubercle bacillus (M. Tuberculosis) and leprocy bacillus (M. leprae)
|
|
|
Ziehl-Neelsen technique
|
procedure for identifying acid fast bacteria
|
|
|
what color do acid fast bacteria stain
|
red, from the fuchsin stain that was not washed away by the acid, all other cells stain blue, which is the color of the counterstain
|
|
|
most common of the spirochete bacteria 2
|
treponema pallidum (causitive agent of syphilis) ; Borrelia (such as borrelia burgdorferi which causes lyme disease)
|
|
|
how do you culture chlamydiae
|
we cant, they are only known to grow intracellularly
|
|
|
most common cause of STD
|
infection with chlamydia trachomatis
|
|
|
describe the features of rickettsiae
|
these are small obligate intracellular parasitic bacteria similar to chlamydiae. They cause RMSF, endemic typhus, and usually require transmission from an arthropod vector (exception being Coxiella burnetti which causes Q fever and can be acquired by inhalation)
|
|
|
L form bacteri
|
mycoplasmas lack cell walls and resmble L form or laboratory formed bacteria
|
|
|
most common pathogenic mycoplasma
|
mycoplasma pneuoniae
|
|
|
Chapter 30
|
Chapter 30
|
|
|
emperic treatment
|
based on clinician knowledge of usual causative agents in certain clinical situations (ie: E coli and uncomplicated UTI)
|
|
|
disk diffusion method
|
test for microbal sensitivity that involves placing a disk soaked in antibiotic on an agar innoculated with a microbe. The distance which the microbe doesn’t grow from the disk gives an estimate of the MIC
|
|
|
does MIC indicate bacteriocidal concentration or bacteriostatic
|
bacteriostatic
|
|
|
MBC
|
minimal bactericidal conentration
|
|
|
proportion of administered dose of drug that reaches circulation
|
bioavailability
|
|
|
for drugs that kill bacteria slowly what do you want to maximize
|
time above the MIC
|
|
|
for drugs that kill bacteria quickly what do you want to maximize
|
AUIC or area under the inhibitory curve, this is achieved by creating a large C max
|
|
|
effect of pH on aminoglycosides, chloramephenicol, erythromyin, and tetracycline
|
decrease effect of (AG, B lactam, erythromycin) increase chloramphenicol and tetracycline
|
|
|
effect of pH, low redox potential and high divalent cation concentration on aminoglycides
|
all decrease
|
|
|
most common antibiotics for allergic responses, why
|
penacillins, cephlasporins and sulfonamides, penacillins cause allergies due to their ready protein binding which can elicit IgE response
|
|
|
some side effects of aminoglycosides
|
impaired renal functions and inner ear toxicity. Renal toxicity can result in toxic levels building up in blood, while inner ear toxicity presents as balance and hearing loss)
|
|
|
stevens johnson syndrome
|
serious skin allergic reaction leading to formation of bullae on the skin and inflammation of eyes/mucous membranes
|
|
|
in the clinical case for this chapter they discuss the effect of rifampin on the patient's warfarin therapy, give a brief explaination of this
|
the rifampin induced faster clearance of the warfarin which lead to hypercoaguability and resulted in thrombophlebitis for the patient
|
|
|
name 2 purposes for prophylactic antimicrobial therapy
|
prevent infection in individuals who have high risk/exposure to exogenous pathogens, prevent commensal organisms from spreading to sterile sites in body (ie post surgically)
|
|
|
Chapter 31
|
Chapter 31
|
|
|
fundamental difference between viruses and other infectious agents
|
viruses are obligate intracellular parasite that carry out replication entirely with host cell machinery.
|
|
|
structure that surrounds viral nucleic acid
|
capsid
|
|
|
nucleic acid + capsid
|
nucleocapsid
|
|
|
2 basic structural patterns for viruses
|
icosahedral and helical
|
|
|
some viruses have this, which surrounds the nucleocapsid
|
envelope
|
|
|
contents of viral envelope (in addition to nucleocapsid) include
|
virus specific proteins, lipids, and carbohydrates, sometimes a matrix protein
|
|
|
adsorption
|
attachment of virus to host cell surface
|
|
|
clathrin coated pits
|
aggregation sites for some viruses such as influenza on the plasma membrane,
|
|
|
these viruses cannot fuse with cellular membranes
|
nonenveloped viruses
|
|
|
uncoating
|
once the virus is adsorpted and releases its payload into the host cell, the capsid is removed to make the viral genome asessable to the cellular transcription/translation machinery
|
|
|
how do ss + RNA viruses such as picornaviruses (polio) and flaviviruses (west nile) produce proteins, reproduce their RNA
|
to produce protein, the + RNA genome simply acts as mRNA and is translated by cellular ribosomes into proteins. To replicate viral RNA, a virus encoded RNA dependant RNA polymerase produces a negative complimentary RNA molecule, in turn this acts as a template to make complimentary + RNA molecules for progeny
|
|
|
how do ss- RNA viruses such as influenza virus produce proteins, reproduce their RNA
|
negative sense RNA cannot act as mRNA. It must be converted to a complimentary positive sense RNA to produce proteins. Since our cells have no machinery for RNA dependent RNA polymerase, the virion must contain this. Once the + sense mRNA is created proteins can be replicated using ribosomes, and - sense RNA can be regenerated for progeny using the RNA dependent RNA polymerase
|
|
|
segmented genomes
|
some viruses have genomes that exist as multiple strands of RNA, often there are individual genes or groups of genes on these strands
|
|
|
how do ds RNA viruses produce proteins, reproduce their RNA
|
like ss -RNA viruses, they must come preloaded with a RNA dependent RNA polymerase. This polymerase takes the neg sense RNA strand and produces a single pos sense RNA strand from which the negative sense strand can be replicated, or ribosomes can use as mRNA to make viral proteins
|
|
|
describe the unique replication strategy of retroviruses
|
retroviruses like HIV are ss + sense RNA viruses however, they come preloaded with a RNA dependent DNA polymerase (reverse transcriptase) which created DNA from the original RNA molecule, this DNA is then incorporated into the host genome where it stays forever, and is transcribed using DNA dependent RNA polymerase
|
|
|
early vs late transcripts
|
in DNA viruses the first (early) transcripts contain regulatory proteins and proteins required for viral DNA replication, while late transcripts are structial proteins of virion
|
|
|
exons vs introns
|
exons contain the gene sequences, introns are junk sequences….just like in our DNA
|
|
|
how does the release of nonenveloped viruses differ from enveloped
|
nonenveloped released when cell lyses, enveloped released by budding
|
|
|
acute vs latent vs chronic viral infections
|
acute is the virus undergoes multiple replication rounds and there is death of host cell. Latent is seen in DNA/retroviruses, and chronic is seen is Hep C where viral particles are still shed following period of acute illness
|
|
|
immunoglobulin that contributes to defense at mucosal membranes such as respiratory and GI tract
|
IgA
|
|
|
iatrogenic inoculation
|
transmission of virus caused by diagonistic or thereputic procedures
|
|
|
horizontal/vertical sprea
|
horizontal spread is between members of susceptable population and vertical is between mother and fetus when virus is carried in germ cell line,placenta, or maternal birth canal
|
|
|
HSV rabies virus and VZV all spread how
|
through nerves using mechanisms involved in fast axonal transport
|
|
|
most important adaptive defense mechanism against viral infections is
|
cell mediated immunity
|
|
|
interellular defense mechanisms against viruses include
|
apoptosis and autophagy (which results in sequestration of virus particles)
|
|
|
early and late cytotoxic defenses against viruses
|
early is from NK cells while later its CTLs and virus specific antibody responses
|
|
|
viruses are delt with by T lymphocytes that express MHC1 or MHC2
|
MHC1
|
|
|
interferons
|
synthesized by host cells in response to viruses that induces the expression of proteins that INHIBIT the protein synthesis machinery to limit viruses ability to replicate
|
|
|
alpha interferon is produced by
|
leukocytes
|
|
|
beta interferon is produced by
|
fibroblasts and epithelial cells
|
|
|
gamma interferon is produced by
|
T cells activated by speciic anigens
|
|
|
Chapter 44
|
Chapter 44
|
|
|
primary treatment for HCV infection (2). These agents were derived emperically
|
interferon and ribavirin
|
|
|
pegylated interferon
|
longer acting interferon used in combonation with ribavarin to treat HCV
|
|
|
explain some of the mechanisms by which ribavirin exerts its antiviral effects
|
1. inhibition of DNA dependent DNA polymerases and some RNA dependent RNA polymerases 2. inhibition of inosine monophosphate dehydrogenase, lowering cellular GTP and restricting nucleic acid synthesis 3. prevention of capping of viral mRNA
|
|
|
limitations of ribavirin
|
toxicity and lack of specificity
|
|
|
gp120
|
viral glycoprotein found in the envelope of HIV that allows it to bind to surface of CD4 T cells
|
|
|
CCR5 and CXCR4
|
coreceptors for HIV that interact with the CD4 T cells after gp120 has bound CD4
|
|
|
how does maraviroc aid in the treatment of HIV
|
antagonizes the CCR5 receptor of HIV, limiting its ability to bind to T Cells
|
|
|
what is gp41
|
HIV transmembrane protein that changes conformation when gp120 binds CD4, this conformational change exposes the fusion peptide and allows for fusion of viral/cell membranes
|
|
|
R5 vs X4 tropic viruses
|
in patients recently infected with HIV, the virus more commonly binds CCR5 whereas patients with advanced disease have the HIV particles bind CXCR4
|
|
|
what is the MOA of Enfurvirtide
|
this drug treats HIV by targetin a specific domain of the HIV gp41 fusion peptide. This prevents the gp41 from undergoing conformation changes nesessary to fuse membranes with the host cell
|
|
|
what do amantadine and rimantadine treat, how do they do it
|
amantadine and rimantadine treat influenza A. They do this by blocking the M2 transmembrane protein in the influenza virus. This protein acts as a hydrogen chanel. Once influenza enters the cell these channels help to lower the pH inside the endosome, creating conformation changes which result in release of viral genome. These drugs block the M2 channel
|
|
|
prototype antiviral drug
|
acyclovir
|
|
|
what is the MOA of acyclovir and why is it effective against HSV
|
it is a DNA polymerase inhibitor specfic to herpes viruses. The reason it is so effective is that the HSV molecule has a thymidine kinase which phosphorylates acyclovir, this activates it. Herpes viruses phosphyorylate acyclovir much more effectively than other viruses, making it a drug of choice for treating these viruses
|
|
|
thymadine kinase
|
activates acyclovir by phosphorylating it. The thymadine kinase of HSV phosphorylates acyclovir at a much larger rate than those of our cells and other viruses
|
|
|
MOA of ganciclovir, what does it treat
|
ganciclovir treats CMV, it works the same way acyclovir does, except it is preferentially phosphorylated by CMV kinases
|
|
|
difference between acyclovir and valacyclovir
|
valacyclovir is a prodrug of acyclovir that is absorbed much better than acyclovir
|
|
|
difference between valganciclovir and ganciclovir
|
valganciclorir is a well absorbed prodrug of ganciclovir
|
|
|
what is penciclovir
|
acyclovir analog with a longer halflife
|
|
|
famciclovir
|
prodrug to penciclovir, it is a longer lasting more well absorbed version of acyclovir
|
|
|
most acyclovir resistant herpes strains have mutations in what
|
thymidine kinase
|
|
|
what are benefits and risks associated with foscarnet
|
it is a phosphonate which inhibits herpesvirus DNA polymerase directly, but it is nephrotoxic
|
|
|
NRTIs and NtRTIs
|
nucleotide/side reverse transcriptase inhibitors, these are the target of much research due to their potential to treat HIV
|
|
|
MOA of NRTIs
|
these drugs lack a 3' hydroxyl required for chain elongation, once these nucleotide analogs are incorperated into the growing chain by reverse transcriptase, chain elongation stops
|
|
|
NNRTIs
|
non-nucleotide reverse transcriptase inhibitors, these work by inhibiting a catalytic step in reverse transcription
|
|
|
raltegravir
|
prototype integrase inhibitor that targets HIV at the step of strand transfer it is refered to as a "INSTI or integrase strand transfer inhibitor"
|
|
|
HAART
|
highly active antiretroviral therapy, this is the standard for HIV treatment and involves using multiple drugs at once (at least 3)
|
|
|
name the class of drugs that prevent release of influenza A and B virus and how they work
|
neuraminididase inhibitors (oseltamivir/zanamivir). These inhibit cleavage of sialic acid, which is essential for influenza release
|
|
|
name the class of drugs that prevent assembly of HIV/HCV
|
protease inhibitors, these prevent cleavage of precursor peptides and prevent the formation of mature HIV proteins
|
|
|
name 2 classes of drugs that prevent entry of HIV into cell
|
HIV fusion inhibitor (enuvirtide) which binds to gp41 and CCR5 antagonist maraviroc which prevents binding of gp120 to CD4
|
|
|
name a class of drugs that prevents viral dissessembly in influenza
|
influenza M2 antagonist (amantidine and rimantidine) which block the hydrogen channel that induces conformation shift and release of influenza genetic material
|
|
|
thymidine kinase activated polymerase inhibitor effective against HSV, CMV
|
acyclovir, ganciclovir
|
|
|
name a drug that directly inhibits CMV polymerase
|
foscarnet (this is a phosphonate drug)
|
|
|
name 3 classes of drugs designed to target HIV replication
|
NRTI/NtRTI , NNRTI, INSTI
|
|
|
Chapter 46
|
Chapter 46
|
|
|
endemic mycoses
|
infections caused by pathogens that are restricted geographically
|
|
|
oppurtunistic mycoses
|
often seen in immunosuppressed patients
|
|
|
subcutaneous mycoses
|
involve skin, subQ tissue, and lymphatics
|
|
|
superficial and cutaneous mycoses
|
common fungal infections limited to skin/skin structures
|
|
|
sterols of fungal cell membrane
|
ergosterol
|
|
|
components of fungal cell wall
|
chitin, mannin, glucan
|
|
|
conditions that favor fungi that cause disease
|
35-37 C
|
|
|
yeast
|
unicellular form of fungi
|
|
|
mold
|
multicellular filamentous form of fungi
|
|
|
how do most yeasts divide
|
asexual budding
|
|
|
filaments that facilatate mold growth
|
hyphae
|
|
|
mass of hyphae is refered to as
|
mycelium
|
|
|
septate/nonseptate hyphae
|
septate are divided by cross walls running perpendicular to length while nonseptate exist as a multinucleated syncitium
|
|
|
dimorphism
|
ability of many fungi to exist as yeast and mold
|
|
|
with most dimorphic fungal pathogens which form is found in environment and which is found in tissues
|
mold in environment, yeast in tissues
|
|
|
conidia
|
asexual fungal reproductive structures
|
|
|
where are conidia found
|
at the tips of growing hyphae on the conidiophore, directly off the hyphae, or within the hyphae
|
|
|
how do fungi reproduce sexuallty
|
throuh development of spores
|
|
|
primary mechanisms that prevent establishment of fungal infections
|
once fungi spread to a tissue neutrophil phagocytosis/killing is usually sufficient
|
|
|
most important host defense against most fungi
|
cell mediated immunity, as evidenced by the high incidence of fungal disease in AIDS patients
|
|
|
Chapter 51
|
Chapter 51
|
|
|
parasites include mostly
|
helminths and protozoa
|
|
|
do protozoa multiply in human hosts, helminths?
|
yes, no.
|
|
|
common protozoan that many americans are infected with, but show no symptoms of disease
|
toxoplasma gondii
|
|
|
disease associated with parasites usually associated with what conditions
|
prolonged, repeated, unusually burdensome infection
|
|
|
zoonoses
|
parasitic infections caused by aents that infect animals such as birds,reptiles,mammals (particularly livestock)
|
|
|
dead end hosts
|
some animal parasites don’t require a development stage in humans and can infect us anyways. This makes us a dead end host for these parasites
|
|
|
swimmer's itch
|
caused by a blood fluke that alternated between birds and snails, when it attempts to infect us it fails to pass the skin and dies, causing a mild itch which resolves spontaneously
|
|
|
why do many protozoa not have an environmental stage of their life cycle
|
with only a cell membrane (no wall) to protect from environment, many cannot survive outside hosts
|
|
|
trophozoite
|
protozoan life stage that involves growth and replication within host by binary fission
|
|
|
cyst
|
protozoan life stage that is dormant and is more resilliant to environment, the cyst form allows for transfer between hosts
|
|
|
how do amebas move? What is their life cycle?
|
they extend pseudopods toward stimulus and stream cytoplasm in desired direction. They alternate between trophozoite and cyst form.
|
|
|
how do flagellates move, where do they usually infect
|
flagellates have flagella (duh). They are mostly intestinal and blood parasites. Glagellates that invade the GI form cysts to resist environment
|
|
|
ciliates
|
protozoa which move with cilia.
|
|
|
what are the apicomplexans/sporozoa and what diseases do they cause
|
these are protozoa which move in a gliding or tractor tread mechanism. Diseases caused by these include malaria and toxoplasmosis
|
|
|
helminths
|
multicellular worms that are considerably larger than protozoa and reporduce sexually
|
|
|
roundworms
|
circular in cross section, can grow up to 20cm, ascaris lumbricoides looks like an earthworm but they have no visible body segmentation
|
|
|
two types of flat worms
|
flukes and tapeworms
|
|
|
flukes
|
ex include schistosoma and fasciola ; these worms are short and nonsegmented
|
|
|
tapeworms
|
segmented worms tht can vary from a few mm to several meters in legnth, a long tapeworm is actually a chain of independent organisms (a colony)
|
|
|
vectors
|
living transmitters of disease, most vectors are arthropods
|
|
|
transmits malaria
|
anopheles mosquito
|
|
|
transmitts sleepin sickness
|
tetse flies
|
|
|
transmitts river blindness
|
black flies
|
|
|
transmitts chagas disease
|
reduviid kissing bugs
|
|
|
reserviors
|
sources of parasites in environment that do not participate directly in the transmission of parasites to humans
|
|
|
how does fecal oral and penetration of unbroken skin usually occur
|
ingestion of contaminated food and water or exposure to wastes in soil/water
|
|
|
how do arthropods transmit infection to humans
|
by biting you, like mosquitos, f**k mosquitos
|
|
|
how do plasmodia species evade immune response
|
antigenic variation, intracellular infection, and supression of cellular immune response
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how do toxoplasma species evade immune respnse
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by infecting intrecellularly
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these organisms camoflouge from immune ditection
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schistosomes
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these organisms cleve antibodies and compliment
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amebas and leishmania species
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this surface factor is necessary for entry of malaria into RBC
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duffy factor
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what immune responses can often be the only manifestations of parasitic disease
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chronic inflammation and hypersensitivity reactions due to leaking of parasitic antigens
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leukocytes responsible for clearing parasitic infections
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eosinophils
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cytokine that triggers eosinophilia, immunoglobulin associated with parasitic infection
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IL-5, IgE
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3 major antiparasitc control strategies
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1. produce drugs for prevention, 2. immunization 3. field control measures
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example of sucessful chemopropholaxysis for malaria
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administration of chloroquine before travel to malaria striken regions was sucessful in preventing infection, however resistant strains of p falciparum have emerged
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how do schistosomes evade the immune response
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they cover themselves with host antigens
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how do trypanosomes evade host immune response
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they alter surface antigens, preventing development of long term immunity
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stage specific antigens and vaccines
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to develop an effective vaccine against parasites, antigens from all parts of life cycle must be accounted for
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Chapter 58
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Chapter 58
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true positive
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when a test correctly predicts the presense of a pathogen
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true negative
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when a test correctly detects the absense of a pathogen
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false negative
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laboratory test is negative in presense of pathogen
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false positive
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laboratory test is positive in absense of a pathogen
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sensitivity
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likelihood that a test will be positive when the pathogen is present
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specificity
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likelihood that a test will be negative when the pathogen is not present
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how to calculate sensitivity
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true positives / (true positives + false negatives) x 100
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how to calculate specificity
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true negatives / (true negatives + false positives) x 100
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positive predictive value
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true positives / (true positives + false positives) x 100
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negative predicitve value
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true negatives / (true negatives + false negatives) x 100
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why is it better to do an acid fast stain than a gram stain on a sputum sample
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gram stain will just display normal microbiota of respiratory/oral tract but an acid fast stain can reveal if mycobacterium tuberculosis is present
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what is a giemsa stain used for
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systemic protozoal infections
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what is an iodide stain used for
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intestinal helminths
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what is a silver stain used for
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detecting systemic fungal pathogens
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how do direct fuorescent antibody tests work
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monoclonal antibodies, specific for a microbe of interest are conjugated to a flourescent compound. If the microbe is present the antibodies will attach to the microbe and flouresce, making them visible with a fluorescence microscope
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why is the sepcificity of most DFA tests low, how can you raise it (see fig 58-2)
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most of the antibodies that are used are polyclonal and bind multiple antigens, meaing there is cross rectivity and other microbes can be included. This raises the instance of false positive lowering specificity. To raise it monoclonal antibodies which bind a single, specific antigen, remove the risk of cross reactivity and reduce false positives
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explain how a thayer martin chocolate agar is useful for detecting gonococci
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the agar is a selective media, designed to inhibit normal microbiota of the genitourinary tract (with antibiotics) but not gonococci
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describe the lysis centrifugation technique for blood culture
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blood sample is placed in solution that lyses RBCs and spun. The dense material is removed and innoculated onto an agar based medium
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in serological testing how is the amount of antibody in a sample quantified
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by progressivly diluting the serum to the highest extent that antibodies can be detected
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explain the basic steps in an ELISA serology protocol
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1. patients serum is incubated with antigen in question on a solid support 2. the unbound antibodies are washed away. 3. antibodies to the antibodies which were in the patients serum are introduced. These are labeled with an enzyme. 4. the amount of activity from the bound enzymes is measured
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explain the western blot procedure
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antigenic molecules from a pathogen are seperated using electrophoresis. The separated antigens are then blotted onto a solid support and innoculated with patient serum. This allows to see what specific antigens are being bound with patients antibodies, and if there is cross reactivity.
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how can physicians determine if a positive serology is due to past or present illness
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they can take titers at two points in time (acute and convalescent titers) or can measure specific IgM antibodies. IgM antibodies appear in acute infection and fade over time
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how do antigen detection tests work
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they are serology in reverse. Specific antibodies are used to try to capture antigens from patient sample. The ELISA procedure can be done to detect antigens as well as antibodies
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how does a competitive assay for antigens work
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a sample is coincubated with a enzyme labeled antigen, which competes for binding to a fixed amount of antibody. If there is a large amount of unlabeled antigen in the patient's sample, it will outcompete the labeled and a color reaction will not occur, this is a positive finding
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how does a DNA probe test work
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a radiolabled short sequence of DNA is added to a sample. The sample is heated such that the double strand of DNA seperates, allowing the probe sequence to bind to the complimentary single strand. Upon cooling the amound of hybridized probe to non-hybridized probe can be quantified.
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what is required for PCR
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2 short primers, dNTPs, and heat stable DNA polymerase, in each heating/cooling cycle the sequence between the 2 primers is replicated
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real time "qPCR"
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PCR where flourescent labeled primers are amplified by increasing cycles of PCR, the amount of time it takes to reach the level of flourescent detection gives insight into how much DNA was present in the original sample, which is useful in detecting viruses in human fluid samples.
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explain the rationale for microarray testing
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bacteria have nonconserved sequences wedged between conserved sequences. If we do a PCR between these conserved sequences with labeled primers we will create DNA which has specific (non-conserved regions in it) that can be visualized with flourescense. From there a microarray with hundreds of known non-conserved sequences spanning many organisms can be tested. The sequence that hybridizes our labeled PCR product will reveal the identiy of the organism in the original sample
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