Vaccines and Antimicrobial Drugs (#2) Flashcards
any molecule or substance that stimulates the immune system to make antibodies against it and activate immune memory (response)
antigen
the substance given to a host (usually by injection) that induces artificial active immunity
vaccine
vaccines act as ______, but do not cause disease
antigens
what kind of immunity do vaccines induce?
artificial active (stimulate B cells to make antibodies + T cells)
inoculation of a host with a vaccine to stimulate protective active immunity; booster may be required to enhance or restore protection
vaccination (immunization)
first vaccine given ever was by who?
Jenner (gave James Smith cowpox for his smallpox)
immune responses after exposure to antigen (2):
- primary immune response
- secondary immune response
immune response that is slow to start; smaller antibody concentration
primary immune response
immune response that is FASTER and is larger; antibody concentration is higher
secondary immune response
vaccines get you through your _____ immune response level
primary (so when you get exposed again, your body responds with the more effective secondary response)
T/F: during your second exposure to the antigen, your immune system is already activated so you should not get sick (or less sick if there’s been mutation changes to antigen = partial protection)
true
T/F: you will always have antibodies leftover after your primary immune response
false (may have none)
what type of immunity includes your body’s first line of defense?
innate immunity
what type of immunity is built up as we are exposed to diseases or get vaccinated?
adaptive
what type of immunity occurs when an individual produces antibodies to a disease through his or her own immune system?
active
what type of immunity occurs when a person is GIVEN antibodies?
passive
purpose of vaccine development =
get antigen into your body to stim. an immune reponse
3 main approaches to making a vaccine:
1) whole-microbe approach
2) subunit approach
3) genetic approach (nucleic acid vaccine)
type of whole-microbe approach vaccines (3):
1 inactivated vaccine
#2 live-attenuated vaccine
#3 viral vector vaccine
type of whole-microbe approach vaccine: flu virus; attenuation; DEAD viruses; can cause you to get sick
inactivated vaccine
type of whole-microbe approach vaccine: still ALIVE but weakened; MMR (measles)
live-attenuated vaccine
type of whole-microbe vaccine: whole microbe approach but taken DNA out (ex: Johnson-and-Johnson vaccine)
viral vector vaccine
type of vaccine: Flu =
inactivated virus (whole-microbe)
type of vaccine: MMR (measles) =
live-attenuated vaccine (whole-microbe)
type of vaccine: Johnson-&-Johnson
viral vector vector
type of APPROACH of vaccine development: only uses the very specific parts of a virus or bacterium that the immune system needs to recognize
subunit approach
type of APPROACH of vaccine development: uses the genetic material for specific proteins – the DNA or RNA; sends in pieces; novavax for covid
genetic approach (nucleic acid vaccine)
type of approach: novavax for COVID
genetic approach
an effective vaccine should do all of the following EXCEPT:
a) cause a primary immune response in the host
b) present antigen to the immune system
c) replace the host’s previous immune memory to the pathogen
d) cause the production of antibodies that will bind to the pathogen
c) replace the host’s previous immune memory to the pathogen
virus that causes COVID-19 =
SARS-CoV-2
the ____ protein on SARS-CoV-2 is an ANTIGEN.
spike
what does the covid vaccine target on the virus?
spike protein (antigen)
what does the spike protein do for the COVID virus?
helps it attach to cells to cause infection
usually viruses mutate and become more transmissible, but not more ______
sever (wouldn’t be advantageous to kill host; no longer could spread)
we look at the _____ of vaccines, not effectiveness bc effectiveness looks at real world impacts (which is too far ahead for us to tell)
efficacy
what kind of genome does SARS-CoV-2 have?
RNA
what kind of vaccine is Pfizer and Moderna (for covid)?
mRNA vaccine
steps of the develop. of mRNA vaccine (Pfizer + Moderna - 6 steps)
1) mRNA with instructions for making the spike protein is developed in a lab
2) put mRNA in a lipid particle
3) mRNA enters the human cell and antigen presents itself (flag)
4) COVID-19 virus spike protein created (B cell recognizes it and then differentiates)
5) spike proteins are recognized by the immune system (prod. specific antibodies + memory cells)
6) if infected, antibodies bind to virus and stop it from replicating
when antigens are presented on the surface of the virus; FLAG; says “hey this cell is infected!”
antigen presentation
what kind of vaccine is the Johnson-and-Johnson vaccine?
viral vector vaccine
steps of the development of a viral vector vaccine (Johnson-&-Johnson - 6):
1) genetic material (of spike protein) inserted into inactive (harmless) virus
2) viral vector vaccine (genetic material put in lipid-molecule)
3) phagocytic cell engulfs harmless virus
4) COVID spike protein created on surface
5) spike proteins recognized by the immune system, which produces specific antibodies against the virus
6) if infected with virus, antibodies bind to virus and stop it from replicating
resistance in a population to a pathogen (disease) as a result of the immunity of a large portion of the population
herd immunity
herd immunity breaks the chain of ______ ______ from one susceptible host to another
pathogen transmission
in herd immunity, the more highly infectious a pathogen, the _____ the proportion of immune individuals needed to prevent disease spread
greater
measles, which is very contagious, requires a ____% herd immunity
95%
you want ___% herd immunity but this rarely happens
80%
compounds used to treat disease by destroying or inhibiting the growth of pathogenic microbes within a host (in vivo)
antimicrobial drugs
types of antimicrobial drugs (3):
- synthetics
- antibiotics
- semi-synthetics
type of antimicrobial drug: CHEMICAL (ex: sulfur drug)
synthetic
type of antimicrobial drug: naturally produced antimicrobial agents (microbial products); produced by bacteria + fungi;
antibiotic
less than __% of antibiotics have clinical significance
1%
antibiotics are _______ into pills or a liquid — NOT _______
purified; NOT modified
type of antimicrobial drug: chemically modified antibiotics (ex: amoxicillin)
semi-synthetic
example of semi-synthetic =
amoxicillin (chem. modified from penicillen)
antimicrobial drugs are classified based on what 3 things?
- molecular structure
- mechanism of action
- spectrum of antimicrobial activity
1st antibiotic ever used; still the most frequently used antibiotic (40% freq)
penicillins
general characteristics of antimicrobial drugs (4):
- selective toxicity
- therapeutic (effective dose)
- toxic dose
- therapeutic index
characteristic of antimicrobial drugs: ability of a drug to kill or inhibit a pathogen while damaging the host as LITTLE as possible
selective toxicity
penicillin targeting peptidoglycan and amino acid linking in the cell wall demonstrates the its high ______ _______
selective toxicity
characteristic of antimicrobial drugs: drug level required for clinical treatment; get to the MIC
therapeutic (effective) dose
ED =
effective/therapeutic dose
T/F: ED50 means 50% of the trial subjects will be successfully effected with this dose
true
characteristic of antimicrobial drugs: drug level at which drug becomes too toxic for patient (produces side effects)
toxic dose
TD =
toxic dose
T/F: TD50 means 50% of the trial subjects will have toxic side effects
true
characteristic of antimicrobial drugs: ratio of toxic dose to therapeutic dose
therapeutic index
the _____ the therapeutic index, the better
larger
for therapeutic index, we want ED to be _______ TD
greater than (ex: morphine is 70:1)
T/F: morphines therapeutic index is 70:1, meaning you have to take 70x more morphine than needed to get toxic side effects
true
usually highly ______ _____ drugs have a higher therapeutic index (good!!)
selectively toxic
who came up with the general characteristics of antimicrobial drugs (selectively toxic, ED, TD, and therap. index)
Paul Irwin
OTHER general characteristics of antimicrobial drugs (5):
- narrow-spectrum drugs
- broad-spectrum drugs
- cidal agent
- static agent
- side effects
general characteristics of antimicrobial drugs cont: drugs attacks only a FEW different pathogens (ex: only goes after gram-pos pathogens)
narrow-spectrum drugs
example of narrow-spectrum drug =
penicillin (but some semi-synthetic forms are consid. broad)
general characteristics of antimicrobial drugs cont: drugs attacks MANY different pathogens (ex: gram-pos + neg or bacteria, fungi, AND other microbes)
broad-spectrum drugs
general characteristics of antimicrobial drugs cont: KILLS microbes
cidal agent
general characteristics of antimicrobial drugs cont: inhibits growth of microbes
static agent
general characteristics of antimicrobial drugs cont: undesirable effects of drugs on host cells
side effects
types of antimicrobial targets (5):
- cell wall synthesis
- DNA gyrase
- protein synthesis (50S inhibitors)
- protein synthesis (30S inhibitors)
- lipid biosynthesis
type of antimicrobial TARGET by: penicillins
cell wall synthesis
type of antimicrobial TARGET by: Quinolones (ciprofloxacin)
DNA gyrase
what type of Quinolone (antimicrobial) targets DNA gyrase ?
ciprofloxacin
type of antimicrobial TARGET: packages DNA; agent inhibits cell to replicate DNA; works against actively growing cells
DNA gyrase
you have probably taken ciprofloxacin for ______
UTI’s
ciprofloxacin goes again’t what type of bacteria?
gram-NEGATIVE
type of antimicrobial TARGET by: Erythromycin (macrolides)
protein synthesis (50S inhibitor)
classification type of Erythromycin =
macrolides
type of antimicrobial TARGET: large ribosome subunit; selectively toxic bc agents go after a ribosome subunit
protein synthesis (50S inhibitor)
large HUMAN ribosomal subunit =
60S
_________ is a semi-synthetic erythromycin
Z-pack
type of antimicrobial TARGET by: Tetracyclines
protein synthesis (30S)
type of antimicrobial TARGET: commonly used for ACNE; small ribosome subunit; long-term use (for now); use a lot for animals
protein synthesis (30S)
human small ribosomal subunit =
40S
type of antimicrobial TARGET by: Platensimycin
lipid biosynthesis
type of antimicrobial TARGET: newly discovered; agents don’t allow for formation of things such as the cell membrane
lipid biosynthesis
T/F: antimicrobials go after cells, whether they’re dead or alive
false (only ACTIVE cells)
antimicrobials go after bacterial _______
components (ex: cell wall synthesis)
gram-_______ are more susceptible to antimicrobial agents
gram-POSITIVE *
types of SYNTHETIC (chemical) antimicrobial drugs (2):
- growth factor analogs
- quinolones
type of SYNTHETIC antimicrobial drug: structurally similar to an essential growth factor; disrupt cell metabolism
growth factor analogs
example of growth factor analog =
isoniazid
growth factor analog; NARROW spectrum; cidal if actively growing + static if dormant
isoniazid
isoniazid resembles ______ (similar structure) which is needed to produce mycolic acid; cell acidently puts isoniazid in place and build mycolic acid WONG (kills TB cells)
nictimomide
isoniazid has a ______ spectrum
narrow
when the cell puts isoniazid instead of nictimomide, it kills ______ cells bc _____ _____ is built wrong
TB cells; mycolic acid
type of SYNTHETIC antimicrobial drugs: interfere with bacterial DNA gyrase; prevents DNA packaging
quinolones
example of quinolone; NARROW spectrum (against gram-negative bacteria); cidal
ciprofloxacin
example of quinolones =
ciprofloxacin
antibiotics from bacteria re _____ products
natural
ciprofloxacin has a ______ spectrum against what?
narrow; gram-negative (like UTI bacteria)
ciprofloxacin is always ____ against cells
cidal (KILLS!)
types of ANTIBIOTICS from bacteria (3):
- macrolides
- tetracyclines
- lipid biosynthesis disruptor
type of antibiotic from bacteria: targets the 50S ribosomal subunit
macrolides
example of macrolides =
erythromycin
example of macrolide; BROAD spectrum – attacks 50S subunit in a LOT of bacteria; static (only prevents growth)
erythromycin
erythromycin has a ______ spectrum and is ______
broad; static
semi-synthetic macrolide
azithromycin (Z-pack)
type of antibiotic from bacteria; targets the 30S ribosomal subunit
tetracyclines
tetracyclines have a ______ spectrum and are ______
broad; static
type of antibiotic from bacteria; targets FATTY ACID biosynthesis
lipid biosynthesis disruptor
example of lipid biosynthesis disruptor =
platensimycin
platensimycin has a ______ spectrum and is _____
broad; static
platensimycin is effective against what 2 very resistant bacteria?
MRS and VRE
trend of antibiotics from bacteria: have a _____ spectrum and are ______ (at least the examples)
broad; static (only prevents growth)
Beta-Lactam antibiotics from fungi (2):
- penicillins
- cephalosporins
who discovered penicillin?
Alexander Fleming
what do Beta-Lactam antibiotics target?
cell wall synthesis (prevent amino acids from linking up = transpeptidation)
beta-lactam antibiotics are effective primarily against what type of bacterium?
gram-positive bacteria (bc gram-neg have outer membrane)
beta-lactam antibiotics are _____ against actively growing cells
cidal
beta-lactam antibiotics have a ______ ring
Beta-lactam
have a different chemical group than normal penicillins; make it BROAD spectrum or less resistant to bacteria
semisynthetic penicillins
types of semisynthetic penicillins (4):
- methicillin
- oxacillin
- ampicillin
- carbenicillin
type of semisynthetic penicillins: TWO; acid-stable (so it can survive stomach acid and still be active after digestion); beta-lactamase RESISTANT
methicillin + oxacillin
enzyme that some resistant bacteria can make to break the beta-lactam ring
beta-lacatamase
type of semisynthetic penicillin: broadened spectrum of activity (especially against gram-negative bacteria); acid-stable; Betal-lacatamase SENSITIVE
ampicillin
type of semisynthetic penicillin: broadened spectrum of activity (especially against Pseudomonas aeruginsoa); acid-stable but ineffective ORALLY; Betal-lacatamase SENSITIVE
carbenicillin
you’re allergic to penicillin if you produce this PROTEIN; binds to penicillin and makes it into an antigen, causing an allergic rxn
Haptin
natural penicillin =
penicillin G
isoniazid is used to treat what?
TB
the acquired ability of a microorganism to resist the effects of a chemotherapeutic agent to which it is normally sensitive
antimicrobial drug resistance
T/F: synthetic and semi-synthetic antimicrobials can be drug resistant as well
true
once resistance originates in a bacterial population, it can be _____ to other bacteria
transmitted
T/F: resistance mechanisms are NOT confined to a single class of drugs; could be a whole class of drugs
true!
erroneous practices ______ for the growth of resistant bacteria; makes problems worse (ex: take antibiotics for a virus-causing disease)
selects
MRSA was transformed to _____
VRSA
when scientists were trying to determine the “super bug,” they isolated a bacterium from a diabetes patient’s foot and realized it was _____
MRSA
bacteria conjugated (type of horiz. gene transfer) _________________ to MRSA to become VRSA
vancomyosin-resistant interocoxide
we can use vancomyosin-resistant interocoxide anymore to treat MRSA anymore so we have to use ______
plantosomyosin
T/F: drug resistance always occurs very slowly
false (can be very quick)
penicillin became resistant to ______ bc bacteria of this disease now produce a beta-lactamase enzyme (which breaks down penicillin)
gonorrhea
T/F: it’s not the antimicrobial that causes the resistance – it SELECTS for those bacteria that are resistant and then they can go on and take over the population (SELECTIVE MECHANISM)
true
resistance mechanisms (how bacteria make themselves resistant to antibiotics - 5):
- reduced permeability
- inactivation of antibiotics
- alteration of target
- development of resistant biochemical pathway
- efflux (pumping out of cell)
genetic basis of bacterial resistance that is very STABLE
chromosomal
genetic basis of bacterial resistance that is not very stable but can easily be transformed to other bacteria
plasmid
if an antimicrobial drug has a high selective toxicity, it means that it will:
a) cause noticeable side effects in the host
b) be bacteriocidal
c) be more active against the pathogen than the host tissues
d) have a narrow spectrum of activity
c) be more active against the pathogen than the host tissues
mechanisms of bacterial resistance (6):
1) target modification
2) preventing entrance
3) inactivation (of antibiotics)
4) efflux pumps
5) alternate pathway
6) impermeability
mechanism of bacterial resistance: changes target of drug/antibiotic (ex: mutation ot ribosome; antimicrobial can no longer find it); get a LOT of resistance from this; can be a small mutation (spontaneous usually)
target modification
target modification usually results from what?
small spontaneous mutation
mechanism of bacterial resistance: produce an antibiotic degrading enzyme; can never come into the cell; EXOENZYME (outside of the cell)
preventing entrance
preventing entrance mechanism of bacterial resistance involves what kind of enzyme?
exoenzyme
mechanism of bacterial resistance: antimicrobial gets INSIDE the cell, but then enzymes inside inactivate it
inactivation
mechanism of bacterial resistance: revolving door; pumps antimicrobials back outside
efflux pumps
mechanism of bacterial resistance: antimicrobials can’t get in (ex: outer membrane or peptidoglycan layer doesn’t let it thru)
impermeability
ORIGINS of drug resistance (3):
- natural immunity genes
- spontaneous mutations
- location of resistance genes
origin of drug resistance: resistance to certain antibiotics so it won’t kill them
natural immunity genes
origin of drug resistance: MOST of resistance
spontaneous mutations
3 locations of resistance genes:
- chromosome
- plasmids (R factors)
- mobile genetic elements such as TRANSPOSONS
location of resistance genes: via horizontal gene transfer; more stable bc plasmids can be lost
chromosome
location of resistance genes: can carry more than one resistance; can be lost
plasmids (R factors)
why are plasmids called “R factors”?
R for resistance
location of resistance genes: copy genes; gene hops from one chromosome to another
mobile genetic elements such as transposons
copy genes =
transposons
made by bacteria and fungi to kill other bacteria and fungi
antibiotics
why would bacteria want to kill other bacteria?
to steal it’s food + outcompete it; great advantage for survival (some even take their DNA)
transmission of drug resistance is thru what process?
horizontal gene transfer
types of drug resistance TRANSMISSION (horiz. gene transfer - 3):
- transformation
- conjugation
- transduction
T/F: resistance comes from using antimicrobials
false (comes from us “selecting” these bacteria that are resistant to drugs)
Suppose you have been suffering from a terrible cold for 10 days and it’s getting worse. What would the doctor say to assure you that you have found a Dr. who is concerned about antibiotic resistance?
“I will call you tomorrow, after I have looked at the bacterial culture results.”
type of horizontal gene transfer/transmission: transfer of free DNA; occurs when a cell dies and another cell takes up their DNA; comes thru cell wall + membrane; “competent cells” do this
transformation
cells able to take up “naked” DNA up from their environment
competent cells
type of horizontal gene transfer/transmission: plasmid transfer; use a pilus to send a plasmid over to another cell; pilus can also carry resistance genes as well
conjugation
type of horizontal gene transfer/transmission: transfer by viral delivery; occurs via a bacteriophage (virus that infects bacteria); mistake for virus – injects resistance bacterial genes instead of viral DNA; gene has to be transferred thru plasmid or chromosomes
transduction
virus that infects bacteria
bacteriophage
sources of antibiotic resistance (5):
- inappropriate prescribing practices
- unregulated sale of antibiotics
- failure to complete courses of antibiotics
- use of suboptimal antibiotic dosages
- use of antibiotics as animal growth enhancers
source of antibiotic resistance: can get antibiotics online
unregulated sale of antibiotics
source of antibiotic resistance: mutant survivors begin to multiply and propagate bc you didn’t kill them ALL
failure to complete courses of antibiotics + suboptimal antibiotic dose
source of antibiotic resistance: most times when you first get sick, it’s a viral infection; ppl take antibiotics for viral infections and don’t take them long enough
inappropriate prescribing practices
____% of sinus infections start as viral
98%
source of antibiotic resistance: giving livestock antibiotics “proactively” to prevent them from getting sick; causes them to get bigger; started to give them antibiotics all the time; resistant bacteria get into the environment when handling raw meat and contaminating veggies (no illegal to treat them proactively)
use of antibiotics as animal growth enhancers
___ out of 1 or 2 million sources of antibiotic resistance will be a spontaneous mutant
1
preventing emergence of drug resistance: give drug in ______ concentrations to destroy susceptible; takes away wall of protection and gets rid of mutants
high
preventing emergence of drug resistance: use antimicrobials only when ________; make sure it’s not viral
necessary
preventing emergence of drug resistance: take full ______ of antimicrobial; not taking suboptimal dose
course
preventing emergence of drug resistance: use ____ spectrum antimicrobials; doesn’t occur as often bc Dr’s don’t culture it; prevents natural flora from becoming resistant to drugs
narrow
preventing emergence of drug resistance: give a _____ of unrelated drugs (controversal)
combination
possible future solutions to preventing drug resistance (2):
1) continued development of new antimicrobials
2) use of BACTERIOPHAGES to treat bacterial disease (attacks bacterial cells, not human cells)