Respiratory Tract Infections and Immunity Flashcards
What are the signs and symptoms of 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 is DALY – Disability-adjusted Life Year
A sum of Years of Life Lost (YLL) and Years Lost to Disability (YLP)
What are the signs and symptoms of pneuomonia
Chest pain
Blue tinting of the lips
Severe fatigue
High Fever
Does pneumonia increase with age?
Yes
More common in men
What are risk factors for pneumonia?
Demographic and lifestyle factors
Age <2 years or >65 years
Cigarette smoking
Excess alcohol consumption
Social factors
Contact with children aged <15 years
Poverty
Overcrowding
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
Specific risk factors for certain
pathogens
Geographical variations
Animal contact
Healthcare contacts
What are common causative agents or respiratory infections?
Bacterial
Streptococcus pneumoniae
Myxoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis
Viral
Influenza A or B virus
Respiratory Syncytial Virus
Human metapneumovirus
Human rhinovirus
Coronaviruses
Describe Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Causative agent of coronavirus disease first observed in 2019 (COVID-19)
Asymptomatic <-> respiratory pneumonia and lung failure.
Up to November 2022
Gives examples of Community acquired pneumonia (CAP)
Bacterial
Streptococcus pneumoniae (40-50%)
Myxoplasma pneumoniae
Staphylococcus aureus
Chlamydia pneumoniae
Haemophilus Influenzae
Examples of typical - Common
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis
Give examples of Hospital acquired pneumonia and Ventilator associated pneumonia
Hospital acquired pneumonia
Staphylococcus aureus
Psuedomonas aeruginosa
Klebsiella species
E. coli
Acinetobacter spp.
Enterobacter spp.
Ventilator associated pneumonia
Psuedomonas aeruginosa (25%)
Staphylococcus aureus(20%)
Enterobacter
Examples of atypical
Mycoplasma pneumoniae, Chlamydia pneumoniae,
Legionella pneumophilia
What are the mechanisms of damage for acute bacterial pneumonia***
Lung injury
Bacteraemia
Systemic inflammation
Treatment
What is Pneumonia
Inflammation and swelling of the alveoli
How do you grade potential bacterial pneumonia?
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 - 7 mmol/L
0: Low severity - home treatment , antibiotics
1-2: Moderate severity = consider hospital treatment
3-4: High severity - urgent hospital admission , empirical antibiotics if life threatening
What are the treatments for bacteria pneumonia?
Supportive Therapy
Oxygen (for hypoxia)
Fluids (for dehydration)
Analgesia (for pain)
Nebulised saline (may help expectoration)
Chest physiotherapy?
Antibiotics
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 are the specific antibiotics for treating CAP and HAP?***
How can you catch pneumonia?
Oropharynx
Strep. viridans
Coagulase neg. staph
Veronella
Fusiforms
Treponena spp.
Beta-haem. strep
Haemophilus spp.
Staph. aureus
Strep. pneumoniae
Nose
Coagulase neg. staph
Haemophilus spp.
Staph. aureus
Strep. viridans
Strep. pneumoniae
What is the human microbiome
What is microbiota
What is commensal
100 trillion microbial cells populate our bodies at every barrier surface
Ecological communities of microbes found inside multi-cellular organisms
Microbes that live in a “symbiotic” relationship with their host. Providing vital nutrients to the host in the presence of a suitable ecological niche
What is an opportunistic pathogen?
A microbe that takes advantage of a change in conditions (often immuno -suppressioWhn).
What is a 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 results in disease
What does the damage to epithelium caused by viral infection do?
Mediator release
Cellular inflammation
Local immune memory
Loss of cilia
Bacterial growth
Poor barrier to antigen
Loss of chemoreceptors
What can cause severe disease?
- Highly pathogenic strains (zoonotic)
- 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 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
Where to viruses infect?
2009 - H1N1 influenza A
Haemogglutinin binds 𝛂2,6 sialic acids
2012 - H5N1 avian Flu
Haemogglutinin binds 𝛂2,3 sialic acids
2019 – SARS-CoV-2
Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2)
Explain how respiratory epithelium is the target and first line of defence?
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 are serotypes?
Viruses/pathogens which cannot be recognised by serum (really antibodies) that recognise another virus – implications for protective immunity
What is 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
Explain types of viral immunity
Antibody mediated immunity
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
Explain types of viral immunity
Antibody mediated immunity
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
Enriched for IgGs
Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space
Influenza vs RSV vs SARS-CoV-2
No re-infection by same strain
Imperfect vaccines:
Vaccine-induced immunity rapidly wanes
Mainly homotypic immunity
Annual vaccination required
Recurrent re-infection with similar strains
No vaccine
Poor immunogenicity
Vaccine-enhanced disease
Very active research field
No prior immunity
Newly licenced vaccine
Waning immunity
Potential for re-infection
Unclear what vaccination regime will be required
What is the leading cause of infant hospitalisation in the developed world?
What are similar viruses at lower prevalence?
What are risk factors?
Bronchiolitis due to RSV
Similar viruses at lower prevalence include hMPV and PIV.
Premature birth
Congenital heart and lung disease
What are treatments for SARS-CoV-2
Supportive Therapy
Oxygen (for hypoxia)
Fluids (for dehydration)
Analgesia (for pain)
Nebulised saline (may help expectoration)
Chest physiotherapy?
Preventative/prophylactic: Vaccines
Major surface antigen – spike protein
Viral vector (e.g. adenovirus vaccine e.g. Oxford/AZ)
mRNA vaccines (e.g. BioNtech/Pfizer)
Therapeutic: 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
What are treatment options for RSV?
Vaccines
Monoclonal antibodies
Anti-virals
