Respiratory tract infections and immunity Flashcards
What are the signs and symptoms of an upper respiratory tract infection?
A cough
Sneezing
A runny or stuffy nose
A sore throat
Headache
What are the signs and symptoms of lower respiratory tract infection?
A “productive” cough - phlegm
Muscle aches
Wheezing
Breathlessness
Fever
Fatigue
What are the signs and symptoms of pneumonia?
Chest pain
Blue tinting of the lips
Severe fatigue
High Fever
What is “DALY”?
“Disability- adjusted Life Year”=
A sum of years of life lost (YLL) and years lost to disability (YLP)
Age dramatically impacts mortality burden, true or false?
TRUE
Pneumonia rates increase with age, true or false?
TRUE
A mix of viral and bacterial causes, can lead to respiratory illness true or false?
TRUE: there is no single dominant pathogen, there can be copathogens: bacteria-bacteria, virus-virus or virus- bacteria
List the demographic and lifestyle risk factors for Pneumonia?
Demographic and lifestyle factors:
Age <2 years or >65 years
Cigarette smoking
Excess alcohol consumption
List the social risk factors for Pneumonia?
Social factors:
Contact with children aged <15 years
Poverty
Overcrowding
List the medical risk factors for Pneumonia?
Medications:
Inhaled corticosteroids
Immunosuppresants (e.g steroids)
Proton pump inhibitors
Medical history:
COPD, Asthma
Heart disease
Liver disease
Diabetes mellitus
HIV, Malignancy, Hyposplenism
Complement or Ig deficiencies
Risk factors for aspiration
Previous pneumonia
List risk factors for certain pathogens, causing pneumonia
Geographical variations
Animal contact
Healthcare contacts
What are the common causative agents for respiratory infection?
Bacterial:
Streptococcus pneumoniae
Myxoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis
Viral:
Influenza A or B virus
Respiratory Syncytial Virus
Human metapneumovirus
Human rhinovirus
Coronaviruses
Give examples of bacteria that cause community acquired pneumonia (CAP):
Streptococcus pneumoniae (40-50%)
Myxoplasma pneumoniae
Staphylococcus aureus
Chlamydia pneumoniae
Haemophilus Influenzae
Give examples of the most common/ typical bacteria for pneumonia
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis
Give examples of hospital acquired pneumonia
Staphylococcus aureus
Psuedomonas aeruginosa
Klebsiella species
E. coli
Acinetobacter spp.
Enterobacter spp.
Give examples of ventilator acquired pneumonia
Psuedomonas aeruginosa (25%)
Staphylococcus aureus(20%)
Enterobacter
give examples of atypical bacteria associated with pneumonia
Mycoplasma pneumoniae, Chlamydia pneumoniae,
Legionella pneumophilia
Describe streptococcus pneumoniae
Gram- positive
Extracellular
Opportunistic pathogen
What are the consequences of bacterial infections in the lower airways?
Whenever the bacteria reach the lower airways, it can cause either:
1. Bronchitis:
- Inflammation and swelling of the bronchi
2. Bronchiolitis:
- Inflammation and swelling of the bronchioles
3. Pneumonia:
- Inflammation and swelling of the alveoli
What other issues can result from pneumonia?
- Lung injury -> arterial hypoxemia -> ARDS/ organ injury or dysfunction (Sepsis/ Deterioration)
- Bacteremia -> organ infection -> organ injury or dysfunction (Sepsis or deterioration) / overactive immune response (deterioration)
- Systemic inflammation -> overactive immune response (deterioration/ organ injury or dysfunction (sepsis)
Treatment -> overactive immune response (organ injury or dysfunction, sepsis, deterioration)
What is the process of Grading potential bacterial pneumonia?
CRB/CURB-65 scoring [initial estimate] (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 - 7 mmol/L
How is bacterial pneumonia treated?
Supportive Therapy:
Oxygen (for hypoxia)
Fluids (for dehydration)
Analgesia (for pain)
Nebulised saline (may help expectoration)
Antibiotics:
1. Penicillins e.g. amoxicillin – beta lactams that bind proteins in the bacterial cell wall to prevent transpeptidation
2. Macrolides e.g. clarithromycin – bind to the bacterial ribosome to prevent protein synthesis
What is the key to increasing the success of antibiotics?
- Combining (if severe)
- Time of administration
What is the human microbiome?
100 trillion microbial cells populate our bodies at every barrier surface
What is meant by “microbiota”?
Ecological communities of microbes found inside multi-cellular organisms
What is commensal bacteria?
Microbes that live in a “symbiotic” relationship with their host. Providing vital nutrients to the host in the presence of a suitable ecological niche.
Can you catch penumonia?
yes; The germs that can cause pneumonia are usually breathed in. People often have small amounts of germs in their nose and throat that can be passed on through: coughs and sneezes – these launch tiny droplets of fluid containing germs into the air, which someone else can breathe in.
What are opportunistic pathogens?
Opportunistic Pathogen: A microbe that takes advantage of a change in conditions (often immuno -suppression).
What are Pathobiont bacteria?
Pathobiont: A microbe that is normally commensal, but if found in the wrong environment (e.g. anatomical site) can cause pathology.
Why do viral infections result in disease?
Viral infection cause:
- Mediator release
- Cellular inflammation
- Local immune memory (unless it’a a first time infection)
- Damage to epithelium (which leads to loss of cilia, bacterial growth, poor barrier to antigen, loss of chemoreceptors)
What causes severe disease?
- Highly pathogenic strains (zoonotic- come from animals, and replicates in humans)
- Absence of prior immunity
* Innate immunodeficiency (e.g. IFITM3 gene variant)
* B cells (antibody- presumably local)
* T cells (correlate with peripheral levels?) - Predisposing illness/conditions
* Frail elderly
* COPD/asthma
* Diabetes, obesity, pregnancy etc
What is meant by viral load?
How much a virus can replicate
Where does H1N1 influenza A virus infect?
Haemogglutinin binds alpha2,6 sialic acids (found in the upper resp tract)
Where does H5N1 avian flu infect?
Haemogglutinin binds alpha2,3 sialic acids (found in the lower resp tract)
Where does the SARS-CoV-2 virus infect?
Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2) [high ACE2 in nasal epithelium and type 2 pneumocytes in the lungs]
Why does SARS-Cov-2 affect smokers more severly?
The virus spike (S) proteins bind to Angiotensin converting enzyme 2 (ACE2)- smokers have more of these receptors
What is the significance of virus binding?
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.
What is the role of different epithelial cells in immunity?
- Tight junctions – prevents systemic infection
- Mucous lining and cilial clearance – prevents attachment, 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. Promotes upregulation of anti-viral proteins and apoptosis.
What is meant by the term “serotypes”?
Serotypes: viruses which cannot be recognised by serum (really antibodies) that recognise another virus – implications for protective immunity
What is an antigen?
any molecule against which antibodies can be generated.
Describe the mechanism of action of antibody mediated immunity
- Humoral immunity
- Adaptive, so dependent on prior exposure
- B cells activated to differentiate into antibody secreting plasma cells
- Different antibody classes provide different biochemical properties and functions
What antibodies are most found in the nasal cavity?
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 antibodies are most found in the bronchi?
IgG:
Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space
Describe the strains of and our immunity against Influenza virus
No re-infection by same strain
Imperfect vaccines:
Vaccine-induced immunity rapidly wanes (changes)
Mainly homotypic immunity
Annual vaccination required
Describe the strains of and our immunity against the Respiratory Syncytial virus (RSV)
Recurrent re-infection with similar strains
No vaccine
Poor immunogenicity
Vaccine-enhanced disease
Very active research field
Describe the strains of and our immunity against the SARS-Cov-2 virus
No prior immunity
Newly licenced vaccine
Waning immunity
Potential for re-infection
Unclear what vaccination regime will be required
Compare influenza with RSV
Influenza:
- Replicates faster (correlates with viral load- replication peaks earlier)
- peaks at day 5 of infection
RSV:
- slower
- peaks at day 6/7
How does RSV bronchiolitis affect infants?
- Leading cause of infant hospitalisation 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.
- still no vaccine
What are risk factors of infants developing RSV bronchiolitis?
- Premature birth
- Congenital heart and lung disease
What are treatment options against viruses?
Supportive therapy:
Oxygen (for hypoxia)
Fluids (for dehydration)
Analgesia (for pain)
Nebulised saline (may help expectoration)
Preventative:
vaccines:
Major surface antigen – spike protein
Viral vector (e.g. adenovirus vaccine e.g. Oxford/AZ)
mRNA vaccines (e.g. BioNtech/Pfizer)
Monoclonal antibodies
Anti-inflammatory:
Dexamethasone (steroids)
Tocilizumab (anti-IL-6R) or Sarilumab (anti-IL-6)
Anti-virals:
Remdesivir – broad spectrum antiviral – blocks RNA-dependent RNA polymerase activity
Paxlovid – antiviral protease inhibitor
Casirivimab and imdevimab - monoclonal neutralising antibodies for SARS-CoV-2
How can resp infections/ virus affect chronic lung diseases?
- Viral bronchiolitis is associated with the development of asthma
- Rhinoviruses are the most common cause of asthma and COPD exacerbations
- High likelihood of secondary bacterial pneumonia after viral infection
