Respiratory tract infectons / immunity Flashcards
symptoms of upper resp infection? 5
A cough Sneezing A runny or stuffy nose A sore throat headache
symptoms of lower resp infection? 6
A “productive” cough - phlegm Muscle aches Wheezing Breathlessness Fever Fatigue
What are the symptoms of pneumonia?
Chest pain
Blue tinting of the lips
Severe fatigue
High Fever
How many deaths annually from acute L resp infection?
. About 3 million deaths
What is DALY?
Disability-adjusted Life Year
A sum of Years of Life Lost (YLL) and Years Lost to Disability (YLP)
Why do acute lung infections only rank 4th in global deaths but 1st in global DALYs?
..
What do pneumonia rates increase with?
age
infant mortality resp illness?
L resp more common
Pneumonia
Bronchiolitis
What are the demographic and lifestyle factors affecting pneumonia?
Age <2 years or >65 years
Cigarette smoking
Excess alcohol consumption
What are the social factors affecting penumonia?
Contact with children aged <15 years
Poverty
Overcrowding
What are the medication factors affecting penumonia?
Inhaled corticosteroids
Immunosuppresants (e.g steroids)
Proton pump inhibitors
What are the medical history factors affecting penumonia? 10
COPD, Asthma Heart disease Liver disease Diabetes mellitus HIV, Malignancy, Hyposplenism Complement or Ig deficiencies Risk factors for aspiration Previous pneumonia
common bacterial causative agents?
Streptococcus pneumoniae
Myxoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis
common viral causative agents? 5
Influenza A or B virus Respiratory Syncytial Virus Human metapneumovirus Human rhinovirus Coronaviruses
What are common community acquired pneuomia?
Bacterial Streptococcus pneumoniae (40-50%) Myxoplasma pneumoniae Staphylococcus aureus Chlamydia pneumoniae Haemophilus Influenzae
What is Streptococcus pneumoniae?
- Gram-positive,
- extracellular,
- opportunistic pathogen
What are examples of hospital acquired pneumonia agents?
Staphylococcus aureus Psuedomonas aeruginosa Klebsiella species E. Coli Acinetobacter spp. Enterobacter spp.
What are ventilator associated pneumonia agents?
Psuedomonas aeruginosa (25%) Staphylococcus aureus(20%) Enterobacter
Examples of atypical Hosptial acquired penumonia agents?
Mycoplasma pneumoniae, Chlamydia pneumoniae,
Legionella pneumophilia
What is bronchitis?
Inflammation and swelling of bronchi
What is bronchiolitis?
Inflammation and swelling of bronchioles
What is penumonia?
Inflammation and swelling of the alveoli
How does pneuomonia lead to ARDS?
Lung injury –> arterial hypoxemia
How does pneumonia lead to sepsis?
bacteremia –>
organ infection –>
organ injury
How does pneuomonia lead to organ injury?
Through systemic inflammation
bacteremia
lung injury
which all leads to detoriation of pulomary, cardio,, neuromuscualr, haem, cognostive etx
How to grade potential bacterial pneumonia?
CRB /CURB-65
Confusion
Resp rate (30+)
Blood pressure <90/60
65. or older
- in hospital add
Urea - 7mmol/L
If CRB is 0?
suitable for home treatments
could give antibiotics
If CRB is 1-2?
consider hospital refferal
if CRB is 3-4?
urgernt hospital admission
empirical antibiotics if life threatening
What supportive treatments are avaibalve for bacterial penuomona?
Oxygen (for hypoxia) Fluids (for dehydration) Analgesia (for pain) Nebulised saline (may help expectoration) Chest physiotherap
What antibiotics are given for bact pneuo?
Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
Macrolides e.g. clarithromycin – bind to the bacterial ribosome to prevent protein synthesis
What is an opportunistic pathogen?
A microbe that takes advantage of a change in conditions (often immuno-suppression).
What is a Pathobiont?
A microbe that is normally commensal, but if found in the wrong environment (e.g. anatomical site) can cause pathology.
WHat bacteria in your oropharync can cause penuomonia?
Strep. viridans Coagulase neg. staph Veronella Fusiforms Treponena spp. Beta-haem. strep * Haemophilus spp. * Staph. aureus * Strep. pneumoniae
What bacteria in your nose can cause pneumonia?
Coagulase neg. staph Haemophilus spp. Staph. aureus Strep. viridans * Strep. pneumoniae
How do viral infections cause disease?
cellular inflammation
- mediator release
- local immune memory
DAMAGE TO EPITHELIUM: - loss of chemoreceptors - bacterial growth loss of cilia - poor barrier to antigen
What causes severe disease?
highly pathogenic strains
absence of prior immunity
predismposing illness/conditions
What may cause absence of prior immunity?
Innate immunodeficiency (e.g. IFITM3 gene variant) B cells (antibody- presumably local) T cells (correlate with peripheral levels?)
What may be examples of predisposing conditions?
Frail elderly
COPD/asthma
Diabetes, obesity, pregnancy etc.
differential diagnosis?
look at slide 28
Where does H1N1 influenza A bind?
Haemogglutinin binds 𝛂2,6 sialic acids
Where does H5N1 avian Flu bind?
Haemogglutinin binds 𝛂2,3 sialic acids
Where do viruses tend to bind in the resp system?
Most respiratory viruses can infect cells throughout the respiratory tract, but tend to preferentially adapt to bind cells of the upper respiratory tract if they have existed in humans for a prolonged time
Where does SARS coV-2 bind?
Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2)
Where are ACE2 in the lungs?
Nasal epithelium
AND
Pneumocytes
- levels increase in smokers
What defences are within the epithelial cells? (5)
- tight junctions
- mucous cilia lining
- antimicrobial
- pathogen recognition receptors
- interferon pathways *activated by viruses, promotes upregulation of anti-viral proteins and apoptosis
What is the upper resp?
nasal cavity
paharynx
What is lower resp?
larynx
trachea
bronchi
What are serotypes?
viruses which cannot be recognized by serum (really antibodies) that recognize another virus – implications for protective immunity
What is antibodiy mediated immunity?
Humoral immunity
adaptive to previous exposure
B cell activated to differentiate into antibody secreting plasma cells
different antibody classes privide different biochemical proeprties and functions
What is the nasal cavity enriched with?
Enriched for IgA
High frequency of IgA-plasma cells
ECs express poly IgA receptor, allowing export of IgA to the mucosal surface
Homodimer is extremely stable in protease rich environment
What is the bronchi enriched with?
Enriched for IgGs
Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space
What is RSV?
Respiratory syncytial virus
compare the vaccines for
influenza
RSV
SARS cov 2
Influenza : Vaccine-induced immunity rapidly wanes
Mainly homotypic immunity
Annual vaccination required
RSV : No vaccine Poor immunogenicity Vaccine-enhanced disease active research field
Covid: Newly licenced vaccine Waning immunity Potential for re-infection Unclear what vaccination regime
Describe the epideiology of RSV bronchiolitis in infants?
- Leading cause of infant hospitalization in the developed world
- 50% of children infected in year 1 of life, all children by year 3.
- 1% develop severe bronchiolitis.
Can repeatedly infect children.
Risk factors for infant RSV bronchiolitis?
Premature birth
Congenital heart and lung disease
usully spready by older siblings
Symptoms of infant RSV bronchiolitis?
- nasal flaring
- chest wall retractions
- hypoxemia
- croupy cough
- expiratory wheezing,
- prolonged
- expiration
- Rales and rhonchi
- Tachypnea with apneic episodes
is it bad if the old and infirm get RSV?
Major cause of progressive lung disease and winter deaths
if a caring adult gets RSV how will it present?
Repeated colds.
Transmitters.
Very rarely severe
What antivirals are avaible?
Remdesivir – broad spectrum antiviral – blocks RNA-dependent RNA polymerase activity
Paxlovid – antiviral protease inhibitor
Casirivimab and imdevimab - monoclonal neutralising antibodies for SARS-CoV-2
What therapuetic treatment is given for antivrials?
Anti inflammatory
Dexamethasone (steroids)
Tocilizumab (Anti-IL6R) or Sarilumab (anti-IL6)
What is analgesia given for
pain
WHat is nebulised saline for?
Nebulised saline (may help expectoration)
What other disease is viral bronchiolitis associated with the development of?
Asthma
What virus are the most common cause of asthma and COPD?
Rhinovirus
What increases the liklihood of secondary bacterial pneumonia?
viral infections
*55% of rhinovirus-infected COPD patients also have bacterial infections
