Respiratory tract infections & Immunity Flashcards
What are the signs and symptoms of Upper respiratory tract infections?
A cough Sneezing A runny or stuffy nose A sore throat headache
What are the signs and symptoms of Lower respiratory tract infections?
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 are some risk factors for pneumonia?
Age <2 years or >65 years Cigarette smoking Excess alcohol consumptionContact with children aged <15 years Poverty OvercrowdingInhaled corticosteroids Immunosuppresants (e.g steroids) Proton pump inhibitorsCOPD, Asthma Heart disease Liver disease Diabetes mellitus HIV, Malignancy, Hyposplenism Complement or Ig deficiencies Risk factors for aspiration Previous pneumoniaGeographical variations Animal contact Healthcare contacts YOU JUST NEED TO BE AWARE OF THESE
What are sone common bacterial causes for respiratory infections?
Streptococcus pneumoniae
Myxoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis
What are sone common viral causes for respiratory infections?
Influenza A or B virus Respiratory Syncytial Virus Human metapneumovirus Human rhinovirus Coronaviruses
What are some bacteria that are involved in community acquired pneumonia ?
Streptococcus pneumoniae (40-50%) Myxoplasma pneumoniae Staphylococcus aureus Chlamydia pneumoniae Haemophilus Influenzae
What are the features of streptococcus pneumoniae?
Gram-positive, extracellular, opportunistic pathogen
What are some bacteria that are involved in hospital acquired pneumonia?
Staphylococcus aureus Psuedomonas aeruginosa Klebsiella species E. Coli Acinetobacter spp. Enterobacter spp.
What are some bacteria involved in ventilator associated pneumonia?
Psuedomonas aeruginosa (25%) Staphylococcus aureus(20%) Enterobacter
What are some typical pneumonias?
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis
What are some atypical pneumonias?
Mycoplasma pneumoniae, Chlamydia pneumoniae,
Legionella pneumophilia
What is pneumonia?
Inflammation & swelling of the alveoli
What is Bronchitis?
Inflammation & swelling of the bronchi
What is bronchiolitis?
Inflammation and swelling of the bronchioles
How do you grade potential bacterial pneumonia?
CRB/65 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
What are the criteria for CRB/65?
0 - low severity, home treatment
1-2 - moderate severity, consider hospital referral
3-4 - high severity, urgent hospital admission, empirical antibiotics if life threatening
What is the supportive treatment for bacterial pneumonia?
Oxygen (for hypoxia) Fluids (for dehydration) Analgesia (for pain) Nebulised saline (may help expectoration) Chest physiotherapy?
What are the Curative treatments for bacterial pneumonia?
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 the key to increasing the success of antibiotics?
Time to administration - for every hour in septic shock survival is reduced by 7.9%.
Use of an effective antibiotic, typical CAP’s may respond to penicillins, Atypical CAP’s require Macrolides.
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 is a Commensal Microbe?
Microbes that live in a “symbiotic” relationship with their host. Providing vital nutrients to the host in the presence of a suitable ecological niche.
Why do viral infetcions result in disease?
Mediator release
Cellular inflammation
Local Immune memory
Damage to epithelium
What damage do viruses inflict on the epithelium?
Loss of cilia
Bacterial growth
Poor barrier to antigen
Loss of chemoreceptors
What causes severe disease in viral infections?
Highly pathogenic strains (zoonotic)
Absence of prior immunity
Predisposing illness/conditions
Which viruses bind to alpha-2 sialic acids?
2009 - H1N1 influenza A
Haemogglutinin binds 𝛂2,6 sialic acids
2012 - H5N1 avian Flu
Haemogglutinin binds 𝛂2,3 sialic acids
Where does SARS-CoV-2 bind?
Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2)
Increased ACE2 in smokers
Where do viruses tend to bind to?
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 your first line of defence against viral infection?
Epithelial cells
What are some mechanisms used by epithelial cells to protect against viral infection?
Tight junctions – prevents systemic infection
Mucous lining and cilial clearance – prevents attachment, clears particulates
Antimicrobials – recognise, neutralize 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.
Define Serotypes:
pathogens which cannot be recognized by serum (really antibodies) that recognize another pathogen.
Where would you find IgA?
Upper respiratory tract,
Able to withstand extracellular environment of the air space well, due to multiple disulphide bridges that prevent rapid degredation. Non-inflammatory, binds and neutralises threats.
Where would you find more IgG’s?
Lower respiratory tract,
circulation comes into closer proximation with air space due to thin walled alveolar space. You can have transfer of IgG to protect lower airways through a vaccine.
Are inflammatory.
How is Antibody mediated immunity carried out?
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
Describe Infleunza:
No re-infection by same strain
Imperfect vaccines:
Vaccine-induced immunity rapidly wanes
Mainly homotypic immunity
Annual vaccination required
Describe RSV:
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.
Similar viruses at lower prevalence include hMPV and PIV.
Risk factors;
Premature birth
Congenital heart and lung disease
Recurrent re-infection with similar strains
No vaccine;
Poor immunogenicity
Vaccine-enhanced disease
Very active research field
Descrive SARS-CoV-2:
No prior immunity
Newly licenced vaccine
Waning immunity
Potential for re-infection
Unclear what vaccination regime will be required
What are the symptoms for RSV infected children?
Nasal flaring Croupy cough Hypoxemia & cyanosis Expiratory wheezing, prolonged expiration rales and ronchi tachypnea with apneic episodes
What are some treatment options for Viral infections?
Supportive Therapy
Oxygen (for hypoxia) Fluids (for dehydration) Analgesia (for pain) Nebulised saline (may help expectoration) Chest physiotherapy
What are some preventative treatment options for viral infections?
Vaccines
Major surface antigen – spike protein
Viral vector (e.g. adenovirus vaccine e.g. Oxford/AZ)
mRNA vaccines (e.g. BioNtech/Pfizer)
What are some antivirals used to treat 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 are some anti inflammatory drugs used in severe viral infection?
Dexamethasone (steroids)
Tocilizumab (Anti-IL6R) or Sarilumab (anti-IL6)
What is the interplay between viral infections and 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.
55% of rhinovirus-infected COPD patients also have bacterial infections
