Immunization and Antibiotics Flashcards
what is immunologic specificity?
the degree to which an antibody recognizes an antigen
what is variolation?
ground up scabs of people infected with small pox and shoot the powder up their nose; 2% chance of death
what virus caused small pox?
VARIOLA
what is cross protection?
milk maids who got cow pox had immunity to small pox
produce the same major antigens
describe vaccines that kill the whole organism
ex. hep A vaccine, SALK VACCINE
pros: easy to produce, many antigens present for a robust response
cons: hard to inactivate
what was the cutter incident?
some batches of the SALK polio vaccine contained the live virus, caused 250 cases of polio
what is live, attenuated vaccines?
ex. BCG (TB vaccine), SABIN polio vaccine
organisms have been weakened in some way
pros: pathogen presented to the right part of the body, allows for a robust response
cons: difficult to produce, cannot give to immunocompromised, cold chain distribution needed
what are subunit vaccines?
ex. streptococcus pneumoniae capsular antigen, viral capsids from HPV, TOXOID VACCINES (tetanus)
selected, purified antigenic components of pathogens
pros: easy to produce, no chance of infection
cons: hard to find protective agent
what are nucleic acid vaccines?
Ex. COVID vaccine
contain mRNA that codes for a specific antigen, wrapped in a lipid layer and injected
mRNA has a short life, rapidly dealt with by NK cells
benefits: easy to manufacture, quick to get to market, NO CHANCE OF INFECTION
cons: cold chain distribution, hesitancy
why are booster shots needed?
first dose causes synthesis of IgM, then IgG
booster shot results in a rapid response, since memory B cells formed during first response
booster ensures sufficient antibodies with sufficient reactivity
describe antigenic changes
some pathogens can change their shape or antibodies
ex. COVID, influenza
describe waning memory
memory T-cells and B-cells do not have an indefinite life span
can lose specificity when they replicate
ex. tetanus shot every 10 years
what are the best type of vaccines?
LIVE ATTENUATED
activates the immune system properly, to the right part of the body, prevents a mild form of the infection being passed onto others
what is herd immunity?
for diseases spread person to person, vaccinating a large part of the population interrupts transmission of the disease
important for immunocompromised individuals
what is vaccine hesitancy?
problematic atm due to social media and a lack of fact checking
people believed Jenner’s vaccine would turn them into cows
measles outbreak in New Brunswick
who actually discovered antibiotics first?
ernst dechesne discovered antibiotic properties of penicillin moulds
who stabilized penicillin?
HOWARD FLOREY and ERNST CHAIN
won nobel prize with femming
who was GERHARD DOMAGK?
german physician, daughter got infection from a pinprick
injected her with a dye called PRONTOSIL, cured her
how does PRONTOSIL work?
SULFA DRUGS
prontosil is metabolized to sulfanilmide in the body, inhibits the enzyme that makes folic acid, inturrupting bacterial metabolism
what was WAKSMAN’S contribution?
screened soil bacteria for antimicrobial activity
discovered STREPTOMYCIN
what is SELECTIVE TOXICITY?
drug is toxic against one part of the pathogen and leaves host alone
ex. targets peptidoglycan, ribosomes
how do bacteriostatic drugs work?
prevent growth, but DO NOT KILL it
suspends growth and buys time for immune system to kick in and kill it
what does antibiotic effectiveness depend on?
organism being treated
attainable tissue levels of the drug
route of administration
how can we measure inhibitory concentration?
serial dilutions of a 96-well plate
E-strips
kirby-bauer disk diffusion
ALL TAKE TIME
what will antibiotics target?
cell WALL synthesis
cell MEMBRANE integrity
DNA synthesis
RNA synthesis
PROTEIN synthesis
METABOLISM
which antibiotics are cell wall inhibitors?
penecillins, cephalosporins, vancomycins, bacitracin, monobactams
what antibiotics are cell membrane inhibitors?
polymyxins, daptomycins, gramicidin
what are cell wall antibiotics?
sugar molecules N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) are made in the cytosol
linked together by TRANSGLYCOLASE enzyme at cell wall
side chains of of adjacent NAM molecukes are cross-linked by a transpeptidase to provide rigidity to the cell wall
different antibiotics will inhibit different steps
what are beta-lactam antibiotics?
derived from fungi, consist of a beta lactam ring struction, of which R groups can be added
transpeptidase and transglycolase are called PENECILLIN BINDING PROTEINS
the ring prevents the microbe from binding to the cell wall properly
describe resistance to beta-lactam antibiotics
INHERITANCE of the beta lactamase gene, ex. New Delhi NDM-1, can be overcome by inhibitors, such as clavulanic acid
INHERITANCE of an altered PBP that does not bind to the antibiotic, ex. MRSA
what does BACITRACIN do?
binds to the bactoprenol lipid carrier and inhibits growth of peptidoglycan chain
only used topically
what does CYCLOSERINE do?
inhibits enzymes that make a percursor peptide of the NAM side chain
ex. TB
what does VANCOMYCIN do?
binds to the D-Ala terminal end of the disaccharide and prevents binding of transglycosylases and transpeptidases
is resistance always a good thing for the microbe?
no, causes slower growth
what drugs affect bacterial membrane integrity?
gramicidin: cyclic peptide that inserts into the bacterial membrane
polymyxin: binds to inner and outer membranes of Gram NEGATIVE bacteria, disrupts inner membrane
daptomycin: aggregates in gram POSITIVE bacterial membrane to form channels
what drugs affect DNA synthesis and integrety?
SULFA drugs: interfere with NA and THF synthesis
QUINOLONES: target topoisomerase (toxic to mitochondria)
METRONIDAZOLE: anaerobic bacteria, nicks DNA at random once activated (tooth infections)
what drugs affect RNA synthesis?
rifampicin and actinomycin D
binds to exit tunnel of bacterial RNA polymerase
halts transcription
what are protein synthesis inhibitors?
interfere with rRNA
ribosomes of prokaryotes are very different from eukaryotes
what is a prokaryotic ribosome made out of?
30s and 50s subunit = 70S ribosome
what drugs are protein synthesis inhibitors?
aminoglycosides: bind to 16s, cause translation misreadings of mRNA
tetracyclines: bind to and distort the ribosomal A site (not given to pregnant women)
what proteins target the 50S subunit?
macrolides and lincosamide: inhibit translocation of growing chain
chloramphenicol: inhibits peptidyltransferase activity
oxazolidinones: prevent formation on 70S complex
streptogramins: bind to peptidyltansferase cites
what is mupirocin?
binds to bacterial enzymes that attach amino acids to the end of tRNA molecules, halting protein synthesis
Gram POSITIVE bacteria
why is antibiotic resistance becoming a problem
exerting SELECTIVE PRESSURE on bacteria
how do microbes keep antibiotics outside the cell?
destroy bacteria before it can enter cell
decrease membrane permeability
pump antibiotics out using specific transporters
how do microbes prevent antibiotics from binding to the target?
modify the target so it cannot bind to the antibiotic
add modifying groups
how do microbes dislodge an antibiotic bound to its target?
ribosome protection or rescue
G+ organisms can make proteins that bind to ribosomes and dislodge or prevent binding of antibiotics that bind near the peptidyltransferase site
how can AMR spread?
mutation, vertical transmission, horizontal transmission
