resp infection and immunity Flashcards
is pneumonia more common in young or old
old( makessense if you think with more deaths from resp inf in old)
what is the severity frequency relationship of colds
they happen at low severity frequently
less prev at high severity
3 escalations of a respiratory infection
upper resp tract inf : cough, runny nose, sneezing, sore throat, headache
lower resp tract: fever, “productive cough pleghm muscle aches
pneumonia
how to differenciate bewteen upper resp tract in fand lower
lower has productive cough with pleghm
muscle aches
wheezing
brethlessness
fever fatigue
and usually not stuffy nose sneezing stuff ect
differenciate w=between lower resp tracta nd pneumonia
chest pain
blue lips
severee fatigua
HIGHH FEVER
in pneumonia
is death from resp tract inf a bigg deal globally?
yes
one of leading causes of death
is resp tract inf higher in list od DALYS or anual deaths?
dalys (1st vs 4th) bc think of so many ppl lose work days ect bc of colds
single factor that impacts mortality burden of reps inf most?
age
smoking
co morbid copd
comorbid heart disease
AGE
HOW is age corelated with detahs
adults above 70 and children below 5
most common resp infection pathogen causing mortality in 28- 1 year olds
RSV
most common resp infection causing mortality in 1-5 year olds
pneumonia
are the infant mortality infections viral bacterial or both?
both
medications that incr your risk of pneumonia
Inhaled corticosteroids
immunosupressants - eg steroids
proton pumo inhibitors
social risk factors for pneumonia
for older ppl, people in contact with <15 yr olds
poverty
overcrowding
demographic risks for pneumonia
below 2 yr and over 65
smoking
excess alc consumption
medical hist risk factors pneumonia
- chronic disease (in any system basically )
- cancer
- if risk for aspiration
- previous pneumonia
specific risk factors of pneumonia for some pathogens
geographical variations
animal contact
healthcare contact
most of the times is a pahtogen detected in resp inf or not?
62% of times not
order of prevalence of viral, bacterial, co viral- bacterial detections
most : viral
bacterial
co viral bacterial
(before covid) order of top 3 most common resp infections
rhinovirus
influenza a and b
s pneumoniae ( strep pneumoniae: so its most common bacterial )
is rsv or corona viruses most common
rsv
differenciate between pandemics and endemics. do pandemics have more deaths?
endemics usually in more specific population whether geographical or other common factor
they are seasonal
does not need many deaths to be an endemic vs needs many detahs to be pandemic (has to be more than average anual deaths from seasonal flu) :
USUALLY historically endemics less deaths but not always for exmaple HIV and smallpox are endemics but has sooo many deaths smallpox is actually the thing with most deaths
virus of smallpox
variola virus
type of virus most threat for pandemic
influenza
corona viruses have been endemics in past, covid was kind of exception since all the pre pandemics in 100 yrs were influenza
what are 2 important classification of pneumonia
community or hospital aquired (general or ventil related) : where you caught infection
and
typical or atypical: symptom related and typical are more common.
note:
the two classifics are not linked, so atipical or typical not linked to where you caught the infection. in fact most examples given for both typ and atyp are in community aquired column
most common causative pathogen for community pneumonia,
hospital pneumonia and
ventilator pneumonia
strep pneumoniae 40-50%
staph aureus
psuedomonas aeruginosa 25 % and staph aureus 20%
examples of typical pneumonia causative pathogens
caused by more common bacteria:
strep pneumoniae
haemophilius influanzae
maroxella catarrhalis
(first 2 are in list of exmaples of community aq pneumonias in prev slide)
example sof pahtogens for atypical pneumonias
caused by less common bacterial species :
Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophilia
why are typical pneumonias more common? a. bc the pahtogens that cause them are more common
b. because the pahtogens that cause them are more dangerous
a
what is a difference between atypical and typical pneumonias in terms of presentaiton
atypical: milder
slower onset of symptoms +
lasts longer = (“ walking pneumonia”)
does the treatment differ for typical and atypical pneumonias?
yes
what is pneumonia?
inflammation and swelling of the alveoli
what are three major complicaitons you an get from pneumonia
ARDS
SEPSIS
DETERIORATiON : DECREMENTS IN PULMONARY, CARDIOVASCULAR, NEUROMUSCULAR, HAMETOLOGIC, psychlogic and othe rfunctions
what is one immediate consequence in blood of the lung injury in pneumonia and what complicaiton is this associated with
arterial hypoxemia
ARDS
how can bacterial pneumonia lead to sepsis
bacteremia, organ infeciton,
and
systemic inflammation
lead to
organ injury or dysfunciton, sepsis
what can cause deterioraiton in bacterial pneumonia
treatmnet and systemic inflammationor organ injury and syfinction
what is the system for grading bact pneumonia and hwo do the points work
CRB/CURB-65 scoring (1 point per item)
Confusion
Respiratory rate – >30 breaths/min
Blood pressure - < 90 systolic and/or 60 mmHg diastolic
65 - 65 years old or older
In hospital add
Urea - greater than 7 mmol/L
supportive therapies for bact pneumonia (3 main plus 2)
oxygen- hypoxia
fluids- dehydraiton
analgesia - pain
nebulised saline
chest physiotherapy
What types of antibiotics are used for community aquired infections? and exmaples (CAP)
usually first penicillins (beta lactams) ex. amoxicillin and then add macrolides ex clarithromycin-
mechanism of penicillins - beta lactams
bind proteins in the bacterial cell wall to prevent transpeptidation
mechanism of macrolides
bind to bacterial ribosome to prevent protein synthesis
antibiotics used for HAP hospital acquired
inf: not severe: doxycycline PO
VS SEVERE Tazocin or gentamicin IV
what are commensal bacteria
bacteria living in a symbiotic relationship with their host.- provide vital nutrients
what are microbiota
ecological communities of microbes found inside multi-cellular organisms
what is the human microbiome
100 trillion microbial cells that populate our bodies at every barrier surface
which bacteria that cause resp infections are found in oropharynx
haemophilus spp.
staph. aureus
strep. pneumoniae
what bacteria that can cause a resp infection found in nose
staph aureus
strep pneumoniae
what is an opportunistic pathogen?
a microbe that takes advantage of a change in conditions (often immunosupression)
what is the name of a microbe that is normally commensal but when found in the wrong environment (eg anatomical site ) can cause pathology?
pathobiont
why was there a questioning of whether we should think about bacterial infections in terms of pathogens?
because bacterial pathogens are always basically opportunistic or pathobiont so infection has more to do with the host and less with the pathogen
is it always relatively clear which individuals will get severe infection and which will get over it more quickly?
no- sometimes two very similar individuals will get very different oucomes (very slight differences might point to one person having the greatest risk but not clean cut at all)
what type of viruses are more highly pathogenic?
zoonotic
what are the virus factors that determine severety of disease
the rna sequence of virus, meaning what virus it is- what type (zoonotic- more severe)
the viral load
what are some host factors that determine severity of disease
1) immune system related: innate immunodeficiency (can be for specific virus or general), b cell, t cell
2) predisposing illness/ conditions: frail elderly, copd/ asthma, diabetes, obesity, pregnancy
what is a huge risk factor for influenz in particular
pregnancy
what is an example of a SNP that increases susseptibility to swan flu and what ethnic group has it more commonly and how much does it incr their risk of severe disease?
IFITM3 GENE VARIANT 25% chance of severe disease for chinese
where do viruses tent to preferentially adapt to bind if they have existed in humans for prolonged time and why?
upper respiratory tract because upper tract which is the most easily accessible has more: a2, 6SA subtype of a2 receptors and they adapt to this subtype instead of the one that exists in greater volumes in lower tract
what is the a2 subtype in upper and lower tracts?
a2,6 sialic acid (SA) IN UPPER ANA a2,3 SA in lower
why is H5N1 avian flu not very good at infecting, but if it gets to lower resp tract it can cause more severe infection?
because birds have more a2,3 sa in their upper airways and avian flu is form birds
what parts of the viruses: influenza a and avian flu bind to the SA receptors in lungs?
haemogglutinin
what part of covid binds on what receptor in resp tract?
spike S protein binds angiotensin enzyme 2 ACE2 on lungs
do influenza and covid target same receptor in lungs?
no
a2,6 SA influenza a vs ACE2 COVID
WHy are smokers more succeptible to covid specifically
bc they develop more ace2 receptors in nasal epitheliuma and in type 2 pneumocytes
role of epithelium in resp infection
its the target of infection and first line of defence
what STRUCTURAL aspects of epithelium help in its role as fisrt line barrier
Tight junctions – prevents systemic infection (prevents viruses getting to circ)
Mucous lining and cilial clearance – prevents attachment, clears particulates
what substances present in epithelium help in first line barrier role
Antimicrobials – recognise, neutralise and/or degrade microbes and their products
Pathogen recognition receptors – recognise pathogens either outside or inside a cell
Interferon pathways – activated by viral infection. Promotes upregulation of anti-viral proteins and apoptosis. – prevents onward
if the “common colds” are caused by such specific virus strains: rhino ect why do we get infected all the time with them?
1) bc our immunity against viruses is heavily reliant on antibodies anddd
antibodies are very specific and each type of thes eviruses has soo many serotypes- (each serotype- dif antibodies)
what is a serotype
Serotypes: viruses which cannot be recognised by serum (really antibodies) that recognise another virus – implications for protective immunity
why is rhinovirus the most common cause of cold? (think abt serotypes)
has the most serotypes
what is the shape/ structure of iga antibody and why is it relevant in resp tract
homodimer - is very stable in protease rich environment
in which part of he resp tract are cells rich in IGA in their plasma
in nasal cavity
how do iga antibodies move form inside cells in nasal cavity to ECs?
ecs express poly IgA receotor allowing export into mucosal surface
wha cells in resp tract are rich in IgG
in alveoli
how do igg antibodies move from in to out cell
thin walled alveolar space allows transfer of plasma iggs into alveolar space
other name for antibody mediated immnunity
humoral immunity
so if we said that in infections the host matters more, does that mean there arent real differences between pathogens?
no. there are important differences but they are very nuanced
explain unique aspects of influenza RSV and covid in terms of re-infection (historically can you get reinfected by same strain? similar? is it common?)
influenza cant get reinfected with same strain (and strains are not that many as in rsv)
rsv soo many serotypes and you get reinfected with similar strains
covid there was no prior immunity
what are some issues with vaccines for each of the viruses covid, influenza, rsv?
inf: vaccine induced immunity wanes rapidly, Mainly homotypic immunity
Annual vaccination required
Poor immunogenicity
Vaccine-enhanced disease
Very active research field
Newly licenced vaccine
Waning immunity
Potential for re-infection
Unclear what vaccination regime will be required
in the days after inoculation with virus, does the viral load of influenza or RSV peak in less days
influenza peaks quicker than rsv
in both influenza and rsv is systemic, rank upper or lower tract for viral load extent
most is upper tract then systemic then lower tract
virus that is leading cause of infant hospitalisation in developed world
RSV
what percentage of children is infected in yr 1 of life? does everyone get RSV as children ?
50%, and yes by the age of 3
what percentage of infants with rsv develop severe form and what is this severe form for infants?
1% develop severe bronciolitis
can children get rsv again after first time?
yes, children can be reinfected
what are some similar viruses to rsv that have lower prevalence?
hMPV and PIV
SYMPTOMS Of severe bronchiolitis in infants
chest wall retractions
nasal flaring (nostril widens in breathing in)
hypoxemia and cyanosis
croupy cough
expiratory wheezing - prolonged expiration- rales ans rhonchi
tachypnea and apneic episodes
risk factors for infant bronchiolitis
premature birth
congenital heart or lung disease
supportive treatment options established for viral infections through covid
oxygen (for hypoxia)
fluids (for dehydration)
analgesia (for pain)
chest physiotherapy
anti viral options established bc of covid
remdesivir - broad spectrum antiviral - blocks rna dependant rna polymerase activity
paxlovid- antiviral protease inhibitor
casirivimab and imdevimab- monoclonal neutralising antibodies for covid
other than antivirals what is an other therapeutic type of drugs that was discovered through covid?
anti-inflammatory
dexamehtasone- steroids
anti IL 6R or anti IL 6: tocilizumab or sarilumab
example of interplay between viral and bacterial infections
during spanish flu, (influenza pandemic) around 1919- people with the flu were more likely to get cerebrospinal menengitis (can be bacterial ) and 50-60% of people who died with spanish flu actually died form other infections
are smokers or copd patients more likely to get a bacteral infection after a viral one?
copd patients - smokers dont have incr risk compared to non smokers
are you more likely to get a bacterial pneumonia after viral infection?
yes
what chronic condition is viral bronchiolitis associated with?
asthma
what virus is the most common cause of asthma and copd
rhinoviruses
