Lecture 6: Gonorrhea, Cholera, and the Flu Flashcards
why is typhi more effective at infecting humans?
pseudogenes (the ones that WOULD be used to infect other organisms) aren’t taking up energy, so it is more efficient at infecting humans!
2 viruses that cause cancer but ONLY in immunocompromsied people
EVB
Kaposis sarcoma
what is the ONLY virus that causes cancer in healthy people?
HPV
rotovirus
intestinal sickness
mostly in small children
daycare center toys primary source of infection bc they put things in their mouths
Typhi or Tymermirium more effective in causing disease in humans/
typhi
typhi or tphymerium more common
typhimurium… being clean pretty much makes typhi a non issue
are the typhi genes lost?
no, just mutated
phenotype of syphillus
chancre… a weeping sore
so its rare, people can see it and feel it so they avoid spreading it
phenotype of chlamydia and gonorrhea
often no presentation… so its way more common
there may be pain or discharge in LATE stages… so its likely you spread it before you show symptoms
evolution of gonorrhea and chlamydia as opposed to things like norovirus
STIs: less presentation of disease leads to more ability to spread
Norovirus and stuff: you shed it in diarrhea and stuff… so you NEED the presentation for the spread
Boswell’s urethritis
he got gonorrhea like 24 times in his life
how gonorrhea differs from other diseases
most diseases (including cold, smallpox ) You get the strain ONCE, then you are immune and don't get it again gonorrhea: you get it over and over and over
treatment of gonorrhea
antibiotics
it goes away in like a day
why can you get gonorrhea multiple times
huge antigenic variation… immune can’t respond to a different thing
it even changes during the time you have it
important thing for gonorrhea
type 4 pili (retractile)
gonorrhea: Turner study in Baltimore
baltimore had highest gonorrhea rate in country
5-18% of the people in Baltimire had infection WITH NO SYMPTOMS … only 2 in 5,000 had disease (symptoms)
it is effective because it rarely causes disease
what caused most loss of manpower in WWI??
gonorrhea!
gonorrhea vaccine?
we don’t have one!
what does gonorrhea infect?
mucousal membranes genital tract rectum throat eyes
other outcomes of gonorrhea if untreated
Pelvic inflammatory disease (PID)
gonococcal arthritis
PID
can occur if gonorrhea untreated
major cause of sterility in women
scar tissue forms in uterus and fallopian tubes
Gonococcal arthritis
gonorrhea gets into other tissues
bacteria grows in space between 2 joints
how do you diagnose gonorrhea??
neutrophils (which make the pus)
diplococci
graph on slide 7…what does it mean?
women could be more sexually active earlier with older partners
younger men may have multiple partners
gonorrhea less of a problems as people age and become more monogamous
disseminated gonococcal infection
when gonorrhea disseminates to other tissues
PID and gonococcal artritis
trends in gonorrhea over time
1941ish: WWII…women more independent, less monogomy
1950s: back to monogomy
60s-70s: free-love, baby boomers go to college, pill, people have more partners
80s: HIV/AIDS, people start having safer sex
gonorrhea men vs. women
men don't have a lot of outcomes other than pain and discharge women: PID, tubo-ovarian abscess, ectopic pregnancy, chronic pelvic pain infertility and (rarely) death :(
gonorrhea rates by state..education?
may not change much :/
DC has highest rate of gonorrhea infection in nation
Women and gonorrhea presentation
40% symptomatic
60% asymptomatic
BOTH can lead to further disease (but in US, symptoms usually lead to treatment)
More on PID
may think that nothing is wrong, pain in uterus may be “normal”
septicemia can lead to shock and death (rarely)
gonorrhea basic infection of cell (really basic)
pili pull on surface of host cell, think no infection
bacteria invade cell
bacteria come out with different surface antigens
gonorrhea pili
pull on cell surface, grab surface receptors and activate them to convince no infection
convince epithelial cells to endocytose the bacteria (which isn’t normal)
what on surface of gonorrhea cell is antigenically variable?
pili!
what is success of gonorrhea based on?
GROUP (not individual bacteria) success
need enough force on outside of cell to get one bacteria in
great variety of antigens to confuse immune system
large infectious dose
gonorrhea: type 4 pili
ADHESION is primary function
send out a bundle of long, stringy pili, then pull in closer (retracting of pili)
grab specific receptors on host cell
cause receptors to signal to the cell to engulf the bacteria
what have we tried with gonorrhea vaccines?
tried to target pili
ths hasn’t worked because they change a TON
PilE
core: a helix in the middle, can’t be targeted
tried to target the parts hagning out, but it didn’t work
why gonorrhea vaccines targeted at pili dont work
antigenic variation
gonorrhea pili antigenic variation
change the part of the pili hanging out
silent pilins: non-expressed genes with open reading frames very similar to pili
every so often when bacteria divides, RECOMBINATION of silent pilin and active pilE
so pilE is constantly changing, we can’t target
theres like a million ways to express pilE
can you get infected with gonorrhea from the same host?
yes, because it is constantly changing
study… people infected with gonorrhea and pili studied
after just a week, a huge amount of diversity among the pili types
and it takes almost a week and a half for symtoms to even show….but they were shedding bacteria the whole times
about every day, there were new variants expressed
so why is gonorrhea so successful?
you are transmitting a ton of variants even before you know you are infected
vaccine types
attenuated heat killed outer membrane preparations purified proteins LPS target DNA vaccines
Adjuvant
a chemical you inject WITH the vaccine to get the immune response you need to the vaccine
basically the innate activation which allows the adaptive response to happen
attenuated vaccine
whole organism missing JUST genes that allow it to establish infection
lab adapted are grown in absence of immune system
or use naturall like the cowpox…one that can’t survive in humans
oldest and most effective…also most dangerous for immunocompromised people
heat killed vaccine
still contains all molecular proteins
but heat causes denaturation of proteins (but primary sequence maintained)
outer membrane preparations
strip antigens off microbe, inject just the antigens and surface proteins into the person
“purified proteins”
purified proteins
single protein infected, you get immunity to that protein
LPS target
targets LPS, pretty effective
DNA vaccines
inject with DNA, get a response to the proteins encoded in the DNA
good for viruses
why do we vaccinate
selfish reasons… you dont want to get sick
MORE IMPORTANTLY: to protect those who can’t get vaccinated and the very old and very young
why we vaccinate flu example
get college kids vaccinated… we get and spread the flu most
but if we vaccinate, we protect the old people we visit
… their immune systems can’t handle flu and they can die
flu vaccine types
injection
spray
flu injected vaccine
Targets: “whole” heat killed virus
pros: safe for all ages
Cons: egg allergies, storage media allergies and rxns
type of immune response: CD4 T cells and neutralizing antibodies
flu nasal spray vaccine
targets: live, attenuated virions
pros: more effective immune response in correct location
Cons: can make ppl with weak immune system sick
type of immune response: CD4 and CD8 T cells and neutralizing antibodies
How to make Flu Vaccine
1) in the lab make a new strain by combining the most common strains and attenuated version in eggs… random recombination of virions will occur
2) grow hybrid strain in cheicken eggs
3) test hybrid vaccine for surface proteins of new strains
4) test effectiveness
5) more production
6) package and send to the world
Flu
multiple different RNA segments make up its genume
grows in people and birds, so we can grow it in eggs
if one cell is infected with 2 variants of virus, random recombination will occur
Flu: H and N
spike proteins on surface that we have immune responses to
how we classify flu strains
