1B respiratory tract infections and immunity Flashcards
What are the symptoms of upper respiratory tract infections?
- A cough
- A sore throat
- Sneezing
- A runny or stuffy nose
- Headache
What are the symptoms of lower respiratory tract infections?
- 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
What does it mean that respiratory infections often display progressive symptomology?
We can go from upper respiratory tract symptoms to lower respiratory tract symptoms over time
Describe the frequency vs severity of respiratory infection
How many deaths do acute respiratory infections cause? How many people have latent TB?
1 in 4 people- 1.4 mil deaths from TB in 2019
Why are acute lung infections the leading cause of disability or DALYs lost?
- Partly because of the age groups they affect
- the fact you can survive an acute infection often but have persistent changes in respiratory tract that is disabling
What is DALY?
Disability adjusted Life Year
A sum of years of life lost (YLL) and years lost to disability (YLP)
What age does most mortality happen for respiratory infections?
- Adults older than 70
- Children under 5
How big of a cause of death are respiratory infections in infants?
- Leading cause of death in below 1 year old and second leading cause of death between 1 and 5
- A mix of viral and bacteria causes of respiratory illness (RSV is main one)
- Pneumonia and bronchiolitis present
What demographic and lifestyle factors increase risk of pneumonia?
- Age <2 years or >65 years
- Cigarette smoking
- Excess alcohol consumption
What social factors are there for pneumonia?
- Contact with children aged <15 years
- Poverty
- Overcrowding
What medications are there that are risk factors for pneumonia?
- Inhaled corticosteroids
- Immunosuppressants (e.g. steroids)
- Proton pump inhibitors
What other conditions are risk factors for pneumonia?
- COPD, asthma
- Risk factors for aspiration
- Previous pneumonia
- Heart disease
- Liver disease
- Diabetes mellitus
- HIV, malignancy, hyposplenism
- Complement or Ig deficiencies
What risk factors would there be for certain pathogens for pneumonia?
- Geographical variations
- Animal contact
- Healthcare contacts
What are the main bacterial causative agents of respiratory infection?
- Streptococcus pneumoniae
- Myxoplasma pneumoniae
- Hameophilus influenzae
- Myobacterium tuberculosis
What are the main viral causative agents of respiratory infection?
- Influenza A or B
- Respiratory Syncytial Virus
- Human metapneumovirus
- Human rhinovirus
- Coronaviruses
HICRH
What is SARS-Cov-2?
- Severe acute respiratory syndrome coronavirus 2
- The causative agent of covid-19
- Symptoms wise it can be asymptomatic all the way up to respiratory pneumonia and lung failure
- 250 mil cases and 5 mil deaths
How do risk factors for lower respiratory tract infection compare to those of covid?
They’re very similar- there are very few risk factors unique to covid
And these risk factors cause a much worse infection
What are the bacterial causes of community acquired pneumonia (CAP)?
- Streptococcus pneumoniae (40-50%)
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Staphylococcus aureus
- Haemophilus Influenzae
What are the bacterial causes of hospital acquired pneumonia?
- Staphylococcus aureus
- Pseudomonas aeruginosa
- Klebsiella species
- E. Coli
- Acinetobacter spp.
- Enterobacter spp.
What bacteria cause ventilator associated pneumonia?
- Pseudomonas aeruginosa (25%)
- Staphylococcus aureus (20%)
- Enterobacter
What examples of bacteria that cause typical pneumonia?
- Strep pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
What examples of bacteria that cause atypical pneumonia?
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Legionella pneumophilia
What is typical pneumonia?
- Most common type
- Caused by most common forms of bacteria
What is atypical pneumonia?
- Less frequent
- Distinct bacterial species (e.g. M. pneumoniae is a simple gram negative bacteria)
- Slower onset of symptoms and milder
- “walking pneumonia”
What mechanisms of damage are there in pneumonia?
Mostly inflammation: bronchitis (bronchi), bronchiolitis (bronchioles), pneumonia (alveoli)
Inflammation and swelling of alveoli- fluid build up and cellular infiltrate
- So type 1 alveolar cells are destroyed
- Stops gas exchange happening
- The inflammation act independent of number of bacteria- sometimes bacteria are cleared but inflammation continues
How do we grade potential bacterial pneumonia?
CRB/CURB-65 scoring (1 point per item)
- Confusion
- Respiratory rate → >30 breaths a min
- Blood pressure → <90 systolic and/or 60 mmHg diastolic
- 65 → 65 years old or older
In hospital we add
- Urea → 7 mmol/L
What supportive therapy is there for bacterial pneumonia?
- Oxygen (for hypoxia)
- Fluids (for dehydration)
- Analgesia (for pain)
- Nebulised saline (may help expectoration)
- Chest physiotherapy
What antibiotics are there for bacterial pneumonia?
- Penicillins e.g. amoxicillin- beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation → gram positive
- Macrolides e.g. clarithromycin- bind to the bacterial ribosome to prevent protein synthesis → gram negative
What is the key to increasing the success of antibiotics?
- The time to administration (for every hour in septic shock, survival is reduced by 7.9%)
- Using an effective antibiotic- typical CAPs may respond to penicillin, atypical CAPs require macrolides
Can you catch pneumonia and why?
No, because a lot of the time the bacteria that cause it are commensal and part of the microbiome
Oropharynx bacteria that cause pneumonia examples
- Staph aureus
- Strep. pneumoniae
- Haemophilus spp.
- Veronella
- Fusiforms
Nose bacteria that cause pneumonia examples
- Strep. pneumoniae
- Staph. aureus
- Haemophilus spp.
- Coagulase neg. staph
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 do opacities on lung X ray mean?
Fluid build up due to bacterial or viral pneumonia
What do viral infections do to cause disease?
- Mediator release
- Cellular inflammation
- Local immune memory
- Damage to epithelium
- Loss of cilia
- Bacterial growth
- Poor barrier to antigen
- Loss of chemoreceptors
What things would mean viruses cause more severe disease?
- Highly pathogenic strains (zoonotic- germs that spread between animals and people)
- Absence of prior immunity
- Innate immunodeficiency (e.g. IFITM3 gene variant)
- B cells
- T cells
- Predisposing illness/conditions
- Frail elderly
- COPD/asthma
- Diabetes, obesity, pregnancy etc
What is important to know about virus binding?
Most respiratory viruses can infect cells throughout resp tract but tend to preferentially adapt to bind cells of the upper respiratory tract if they’ve existed in humans for a long time
Where do H1N1 (influenza A) and H5N1 (avian flu) bind?
- Haemagglutinin on H1N1 binds to alpha 2,6 and H5N1 binds to alpha 2,3 sialic acids on epithelial cells
- alpha 2,6 SA are highly expressed in upper respiratory tract e.g. nose and pharynx but low in lower resp tract
- alpha 2,3 SA are highly expressed in lower respiratory tract e.g. nasopharynx but low in higher resp tract
What does the binding of H5N1 mean in terms of transmission and pathology?
- Hard for it to transmit since it can’t replicate in nose and upper airways
- It can cause a lot of damage and inflammation in gas exchange surface however
Where does SARS-CoV-2 bind?
- Binds to angiotensin converting enzyme 2 (ACE2) with its spike protein (S)
- ACE2 is expressed highly in nose and also in type 2 pneumocytes in lungs- means lots of nasal symptoms e.g. anosmia, but there’s also high risk of pneumonia
How does respiratory epithelium act as first line of defence against pathogens?
- Tight junctions: prevents systemic infection
- Mucous lining and cilial clearance: prevents attachment and clears particulates
- 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 and promotes upregulation of anti-viral proteins and apoptosis
What is a serotype?
Viruses to which you need to mount a unique antibody response- they can’t be recognised by serum (antibodies really) that recognise another virus- implications for protective immunity
What kind of antibody is common in upper respiratory tract?
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 kind of antibody is common in lower respiratory tract?
IgG
- Thin walled alveolar space allows transfer of plasma IgGs into alveoli
What is a potential issue with too much IgG?
Too much inflammation and damage in exchange surfaces
Compare influenza, RSV and SARS-CoV-2 in terms of immunity
- Influenza- no reinfection by same strain
- RSV- recurrent reinfection with similar strains
- SARS-CoV-2- no prior immunity
Compare influenza, RSV and SARS-CoV-2 in terms of vaccine
- Influenza- imperfect vaccines since immunity from them wanes, it’s mainly homotypic immunity and annual vaccination is required
- RSV- no vaccine, poor immunogenicity, vaccine-enhanced disease, very active research field
- SARS-CoV-2- newly licensed vaccine, waning immunity, potential for reinfection, unclear what vaccination regime will be required
What is the leading cause of infant hospitalisation in developed world?
Respiratory syncytial virus (RSV)
- 50% of children infected in year 1 of life, all children by year 3
- 1% develop severe bronchiolitis
- Can repeatedly infect children
- Similar viruses at lower prevalence include hMPV and PIV
What are the symptoms of RSV in infants?
- Nasal flaring
- Croupy cough
- Hypoxemia and cyanosis
- Chest wall retractions
- Tachypnoea with apnoeic episodes
- Expiratory wheezing, prolonged expiration, rales and rhonchi
How do we treat RSV in infants?
Give oxygen which usually helps sort it.
What are the risk factors of RSV?
- Premature birth
- Congenital heart and lung disease
What does age dependence mean in terms of RSV?
- Children- very good at being infected and spreading infection
- Adults- good at picking up viruses and getting repeated colds and spreading it to elderly
- Old and infirm- major cause of progressive lung disease and winter deaths
What supportive therapy do we give for viral treatment?
- Oxygen (for hypoxia)
- Fluids (for dehydration)
- Analgesia (for pain)
- Nebulised saline- may help expectoration (spitting/coughing up stuff)
- Chest physiotherapy
What preventative measures are there for viral infections?
- Vaccines- e.g. for covid 19 the major surface antigen is spike protein
- Viral vector
- mRNA vaccines
What anti inflammatory meds are there for viral infections?
- Dexamethasone (steroids)
- Tocilizumab (anti-IL6R) or Sarilumab (anti-IL6)
What anti-virals are there for viral infections?
-
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 do viruses set the scene for?
- For bacterial infections esp bacterial pneumonia
- 55% of rhinovirus infected COPD patients also have bacterial infections
How do viruses interplay with other lung diseases?
- High likelihood of secondary bacterial pneumonia after viral infection
- Rhinoviruses are the most common cause of asthma and COPD exacerbations
- Viral bronchiolitis is associated with the development of asthma
