infectiuo Flashcards
effect of virus on the lung
cellular inflammation
local immune memory
loss of chemoreceptors
poor barrier to hygiene
promote bacterial growth as immune system fights virus cant fight bacteria
loss of cilia - less able to clear bacteria
mediator release
microbiomes
in lung and pharynx as dense as on skin
these bacteria cause pneumonia
common cold agents
rhinovirus coronaviruses influenza viruses parainfluenza viruses resp syncytial virus adenovirus enteroviruses mycoplasma chlamydia exchange between hosts through air virus previously been GI - evolved because of ease of transmission
community acquired pneumonia
eading infectious cause of hospitalisation and deaths in US adults
exceeds $1obillion annually
cooperation between bacteria and virus in the disease - influenza A and B, and resp syncytial virus present
what causes hospital acquired pneumonia
staphylococcus aureus 28% pseudomonas aeruginosa 21.8% klebsiella species 9.8% E coli 6.9% Acinetobacter 6.8% Enterobacter 6.3%
what causes CAP
strep pneumonia - classic presentation: cough, rusty sputum, cold sore
myxoplasma pneumonia - incidious atypical disease
staph aureus - people who are sick in other ways/immuneparetic
chlamidophilia pneumoniae - rare
haemophilus influenza - people with asthma, colo9nised with pneumonia after a viral infection
typical V atypical pathogens in CAP
typical - streptococcus pneumoniae, haemophilus influenzae, Moraxella catarrhalis
atypical pathogens - mycoplasma pneumoniae, chlamysia pneumonae, legionella pneuomophilia
atypical not covered by penicillins - need additional agents eg macrolides
pneumonia and age
after 70 the presenting rate of pneumonia increases
but younger eg 60, there is a higher fatality rate in the people who get the condition
age risk factor because of susceptibility to the virus
risk factor for pneumonia
age <2, >65 smoking alcohol contact with children <15 poverty and overcrowding - confound with passive smoking inhaled corticosteroids immunosuppressants - steroids proton pump inhibitors COPD asthma heart disease liver disease DM HIV malignancy hyposplenism complement or Ig deficiencies risk factors for aspiration previous pneumonia geo variations animal healthcare contacts
symptoms of pneumonia
hypoxic febrile - temp 38degrees crepitations - crackle in lungs new respiratory symptoms orb signs pleuritic chest pain confused new X ray changes
what is pneumonia a disease of
interstitium
affect GE
investigations for CAP
chest xray - could be pneumponia even if normal
blood test - full count - see if responding should be neutrophils and WBC, check urea electrolytes liver func and C reactive protein - check for risk of combined disease part of the septic syndrome
arterial blood gases - how sevele lung desaturation is and look for lactic acidosis
microbiological investigations - sputum culture, blood culture, urine antigen tests for legionella pneumophilia and streptococcus pneumonia
guidelines for diagnosing pneumonia
acute lower resp tract syndrome
new focal chest sign and signs on X ray
>1 systemic feature eg fever, shiver ache, pain, temp> 38degrees
no other explanation
CRB 65 severity score
1 point for every feature confusion resp rate >=30/min SBP <90 or DBP <=60mmHg >=65years 0 = low severity - home and AB 12 - moderate, consider hospital 3-4 high severity - urgent hospital, empirical AB if life threatening, may need ventilation consider social setting and home support
supportive therapy for pneumonia
oxygen - for hypoxia fluids for dehydration analgia for pain nebulised saline - may help expectoration chest physiotherapy
AB therapy that is given for pneumonia
low severity - amoxicillin with doxycycline - effective and low side effect profile - especially with haemophilus
severe - benzylpenicillin IV or telcoplanin and clathiro PO
for 5-7 days
7-14 days for atypicals
time frame of delivery of AB for pneumonia
crucial
in severe AB delivered as soon as possible
for every hour dekay in septic shock - chance of survival reduced by 7.9%
duration 1wk
Influenza pandemic
helitrope hue
could detect bacteria - haemophilus influenza
show association with bacterial colonisation and pneumonia
treatment for flu
Tamiflu and IV clarithromycin early
otherwise need prol0ngued ventilation
signs of flu
fever cough aches breathless at rest nausea increased SOB at rest
what causes severe disease
RNA sequence
viral load
DNA
environment
cause epithelial damage and storm of mediators
secondary bacteria infection
from host and virus - host genetics - variation in IFITN3
what causes sever flu
highly pathogenic strains - zoonotic ijnnate immune deficiency - IFITN3 local absence of B cells absence of T cells frail elderly COPD asthma DM obesity pregnancy V young
global changes in RSV and flu prevalence per month
swing between N and S hemispheres
RSV slightly predates flu
influenza
no reinfection by the same strain imperfect vaccines homotypic immunity vaccine induced immunity fades annual vaccine required perfect virus - runs away from immune system by evolving
RSV
infectious form is filamentus recurrent reinfection with similar strains controls the immune system no vaccine poor immunogenity vaccine enhanced disease researched field relatively stable but does evolve - now have niche strains
RSV broncholitis
caused by RSV
affects babies
commonest cause of admission in infancy in developed countries
1/3 beds in winter
airways full of inflammatory cells - blocked - stop airflow
RSV broncholitis clinical features
chest wall retractions tachypnea with apneic episodes expiratory wheezing prolonged expiration rates and rhonchi croupy cough hypoxemia and cyanosis nasal flaring
Age and RSV
children - infantile bronchitis - causally related to wheeze, older siblings spreaders
transmitted from children to older people
when they get admitted already had it for 3wks
when tested for it its already gone
old people - major cause of progressive lung disease and deaths
adults - colds, transmitters but not severe
RSV vaccine
nasal spray not immunogenic enough
novavex - injected nanoparticle into pregnant women, effective against severe disease but not common - overnight drop in stock market
symptoms and viral load for RSV and flu
RSV more delayed disease
communication between virus and the mucosa
bacterial loads in COPD patients infected with rhinovirus
bacteria level climb with virus level
relationship between bacteria and virus
lung not sterile - contain organisms that are likely to casue pneumonia
bacterial infection likely to be caused by viral pathogen
location of airway diseases
allergic rhinitis - upper airways
bronchi - asthma
allergic alveolitis - alveoli
immunological hypersensitivity
IgE mediated - atopic diseases, hayfever, eczema and asthma
non IgE mediated - allergic diseases - farmers lung
non-immunological hypersensitivity
intolerance
enzyme deficiency - lactase DH
pharmacological - aspirin hypersensitivity
allergic rhinitis
hayfever 25% prevalence in UK 40% world wide seasonal allergy 12-15% children effect on exams - reduced QoL polysensitised because of travel sleep deprivation reduced productivity runny nose, sneeze, congestion, red and watery eyes
allergy
exaggerated immunological response to allergen - inhaled, injected, swallowed, in contact with skin/eye
mechanism
in some diseases some of the time, others all the time
mechanism of allergy
biophysical response
early hypersensitive response - 5-30mins eg sneeze, mast cells
late hypersensitivity response - 8-12hrs - nasal congestion, eosinophils make IL 5 - recruit T cells
T helper type 1
for virus, bacteria, fungi, protozoa Th17 cells NK cells cytotoxic t cells IgM IgA IgG
T helper type 2
for helminths and ectoparasites (ticks) IgE IgG1 innate lymphoid cells eosinophils mast cells basophils activated macrophages
pathophysiology of allergic rhinitis
sensitisation then subsequent exposure
nasal epi already damaged
allergen seep in
DC capture allergen
migrate to lymph node
stimulate ILC2 cells - produce IL5 and IL13
help T cell prime and mature to T follicular helper cell
TfH prime B cell for proliferation and differentiation
into plasma cells
make IgE
sensitise mast and basophils in target by cross linking them
subsequent exposure = degranulation
Type 2 immune response
IL4
Il5 - survival factor for eosinophils
IL13
cytokines
atopy
hereditary predisposition to produce IgE Ab agaiunst common env allergens
atopic disease: allergic rhinitis, asthma, atopic eczema
characterised by Th2 cells and eosinophils
can be atopic but not allergic - don’t express symptoms
allergic march
through age - asthma increase gradually
hayfever - exposed to 3 seasons before prevalent
causes of allergic rhinitis and asthma
house dust mite cats dogs Alternaria cockroach horses
asthma
effects 8-12% population
eosinophil/neutrophil
L5
inflamed lung from allergen and infiltration of cells
phenotypes of asthma
based on control and severity:
intermnittent, mild, allergy freq important
presistant, manageable allergy often important
chronic, severe, uncontrolled
based on endotype or endo-phenotype:
allergic, atopic, eosinophilic
neutrophilic
endotype
subtype of condition
defined by distinct pathophysiological mech
extrinsic allergic alveolitis
0.1% pop exposure to allergens allergen captured by Ab complement, chemotactic factors, neutrophils, macrophages, fibroblasts hypersensitivity response cause inf response
examples of extrinsic allergic alveolitis
farmers lung - mouldy hay
bird fanciers lung - bird dropping
air conditioners lung - air conditioner mould
mushroom workers lung - mushroom compost
coffee workers lung - unroasted coffee beans
millers lung- infested flour
hot tub lung - bacterial contamination
treatment of allergic disease
allergen avoidance
anti-allergic med - antihistamine(80%pop)/nasal steroids
immunotherapy - desensitisation/hyposensitisation
prevalence of allergic rhinitis
ww 40%
uk 23%
Belgium and france highest
what does treatment of allergic rhinitis depend on
type of condition
mild intermittent - start H1 blocker, allergen avoidance
mod/severe int - start intranasal and immunotherapy
mild persistent
mod/severe persistent
noon and freeman
mash up pollen
treat hayfever by immunisation
patients did better
investigating immunotherapy
RCT
practicality - incremental dose over 12 wks
maintenance over 3yrs
only can demonstrate if good pollen season
types of allergen immunotherapy
tablet - for 3yrs daily - compliance issue
subcutaneous - have to monitored for a day, exposed to allergen - not risk free
allergen immunotherapy +ve
effective
long lasting
allergen IT -ve
occasional severe rn
time consuming
standardisation problems
mechanism of IT
alter DC
make IL 10 and IL 27 - shift to type 1 response - immune deviation
interferon gamma produced
Treg cells produced - suppress proallergic response and casue production og IgG - capture antigen
IgG compete with IgE - stop IgE fascilitating cross link between basophils and eosinophil
remove IgG - remove response
add it back - response returns
studies for IT
suppression of TH2 for yr 1 and 2, symptoms and TH2 appear again in 3rd yr
measure IL5 - type 2, Inf gamma - type 1 - evaluate immune deviation
measure IL 10 - measure Trg response
take 12 moths for immune deviation
3month for Treg
biopsy of allergic area - see T cell in mucosa
correlation between symptom, cell and cytokine to see if there is a correlation
2 months ago
IL 35
member of IL12 superfamily
bind to P35, Ebi3
receptor - IL12Rbeta2, gp130
STAT4 and STAT1
suppress type 2 response
supress T cekll response - so late allwergic response
suppress B cell response making IgE - stop basophil and mast cell bind - stop early phase
make IL10 - suppress cytokines, monocytes making TNF-a, Th2, Th1 diff, Tr1 induction, IgE. induce IgG and Foxp3+ Treg cells
antibodies
immunological marker in term sof exposure
produced by Breg
measure func of Ab
IgG compete with OgE
biomarker of compliance and clinical response
have IT = more IgG
how to B cells and T cells communicate
FceRII (CD23) on B cell bind to allergen and IgE complex
internalised
present as MHC class 2 to T cell
not when IgG compete
