Infection of the Respiratory Tract

• Is the lung sterile?

  -No

  -it has its chracteristic microbiota that is altered in diseases e.g infections, asthma, COPD

  
• What is the anatomy for the upper respiratory tract?

  
• What is the anatomy for the lower respiratory tract?

  
• Which group of people are more likely to get respiratory infections?

  Children + Elderly (65+)

  
  

  -Diseases are usually more severe in these age groups

  
  

  -These groups act as reservoirs and vectors of disease (more transmission)
• What are the major respiratory pathogens in the young?

  RSV,Bortetella pertussis,Streptococcus pneumoniae,Haemophilus influenzae b (Hib)

  
• What are the host innate responses to respiratory microbes and what are their functions?

  Mucus- trapping microbes/barrier

  
  

  Mucus flow- removal of microbes

  
  

  Epithelial cell tight junctions- barrier (preventing microbes penetrating between them)

  
  

  Air flow- removal of microbes

  
  

  Commensal microbiota- niche occupation

  
• What effector molecules are produced by the host innate responses and what are their functions?

  
• Why don't epithelial cells have pathogen recognition receptors on their surface?

  -Because there's a commensal microbiota in the lungs.

  
  

  -So you don't want to respond to the microbes on the surface or else that will lead to hyperinflammation in the lung, causing damage.

  
  

  -Instead, epithelial cells have these receptors internally
• What is the second role of epithelial cells in mucosal immunity apart from microbial recognition?

  Cytokine production:

  
  

  -Once a pathogen is detected, one of the first things to happen is an increase in IL-8 production & you'll see the upregulation of surface ICAM 1 & 2 expression

  
  

  -ICAM 1 + 2 = chemokines which will recruit T cells, neutrophils and macrophages to respond to the microbe.

  
  

  -Other chemokines will also be produced e.g. MIP1-alpha

  
  

  -Pro-inflammatory cytokines will also be produced e.g. IL-1alpha, IL-1beta etc.

  
• What can epithelium infection result in?

  -Functional impairment (epithelium cells dont function as they usually do)

  
  

  -Defects in cilia action, mucus movement

  
  

  -Loss of barrier function

  
  

  -Mucus hyper-secretion

  
  

  -Pro-inflammatory cytokine & chemokine release (could lead to cytokine storm)
• Are different regions of the respiratory tract susceptible to different types of microbe/infection?

  Yes, upper respiratory tract infections are mostly viral & lower respiratory tract infections are mostly bacterial
• What are the most common respiratory tract viral infections to occur?

  -Common cold

  -Flu

  -Respiratory Syncitial Virus (RSV)
• What group of viruses causes the most colds by far and what other viruses cause colds?

  Rhinoviruses (accounts for ~60% of colds)

  Coronaviruses are 2nd place, accounting for 15% of coldsOther agents include influenza viruses, RSVs & sporadically, adenoviruses
• How many different serotypes are there of rhinoviruses and coronaviruses that cause the common cold?

  -Over 100 different serotypes of rhinovirus

  
  

  -2 serotypes of coronavirus
• What family is rhinovirus from?

  Picornaviridae
• What is the biological structure of a rhinovirus?

  Non-enveloped, single-stranded, +ve RNA genome

  
• What are symptoms of the common cold caused by rhinoviruses?

  Coughing, sneezing, hypersecretion of mucus, but rarely fever
• Can you generate protective neutralising anti-viral antibodies against rhinoviruses?

  Yes, but there are ~150 different serotypes & within those serotypes there will be alterations & mutations, the chances of you being protected against the next virus that will infect you are very slim
• What do the major & minor viral groups from rhinoviruses bind to?

  -The major viral groups (RV-A & B) bind to ICAM-1 on epithelial cell

  
  

  -Minor group viruses bind to low-density lipoprotein receptor (LDLR)
• Which family is RSV (respiratory syncytial virus) a member of?

  Paramyxoviridae
• What is the structure of RSV?

  Single-stranded, -ve strand RNA virus (RNA needs to be reverse-transcribed & converted into a +ve strand before it can act as mRNA)
• How big is the genome of RSV?

  ~15,200 nucleotides

  11 sub-genomic mRNAs

  
• Which groups of people are more likely to get RSV?

  -Elderly - Often fatal, wheezing = progressive hypoxia

  
  

  -Infants - can lead to bronchiolitis, largest cause of hospitalisation in infants

  
• What is RSV bronchiolitis?

  -Infection and inflammation of bronchioles

  
  

  -Buildup of mucus and swollen mucus membranes; wheezing from partial obstruction

  
• How do you treat RSV?

  Neutralising antibody to prevent infection (Synagis/Palivizumab)- only used in high risk patients because it's too expensive

  
  

  Vaccination
• What is the problem with RSV vaccines?

  -Repeated infection can occur with RSV even with an adapted immune response.

  
  

  -Neonates and infants respond poorly to vaccines

  
  

  -Vaccine enhances wrong immune response, exacerbates diseases and causes pathology

  
• Which family is Influenza a member of?

  Orthomyxoviridae

  
• What is the structure of influenza virus?

  -Enveloped, single strand, -ve RNA genome made up of 8 'chromosomes'.

  
  

  On the envelope, there are 2 key surface proteins:

  
  

  -Neuraminidase (removes virion surface glycoproteins)

  
  

  -Haemagglutinin (which helps bind to its target cells)

  
• Describe the transmission & pathogenesis of the influenza virus.

  
• How does a cytokine storm cause respiratory failure?

  -Inflammatory cell recruitment + pulmonary oedema

  
  

  -Lung damage + air way occlusion (build up of fluid due to oedema)

  
  

  -Acute respiratory distress syndrome

  
  

  -Death
• What is antigenic drift & antigenic shift in influenza virus?

  Antigenic drift:-Minor changes from point mutations-Slow, continuous process-Some protection carried over from previous infections-Associated with epidemics (regional outbreak)

  Antigenic shift:-Major changes in multiple genes, RNA segments exchanged between viral strains.-Rapid/Sudden process-No protection from past infections-Associated with pandemics (worldwide)

  
• How does COVID-19 relate to SARS-CoV & MERS-CoV in terms of lethality & transmissibility?

  COVID-19 is less lethal but has a higher transmissibility
• What is the host receptor of SARS-CoV-2?

  Host receptor is ACE2 which is present on epithelial cells, endothelial cells & macrophages

  
• What are the main target cells of SARS-CoV-2?

  -Airway & alveolar epithelial cells

  -Vascular endothelial cells

  -Alveolar macrophages
• How is SARS-COV2 transmitted?

  -Mainly through droplets and aerosols (smaller than 5um diameter which them becomes airborne)

  -Direct contact

  -Indirect contact

  
• How is SARS-CoV-2 different to SARS-CoV?

  Unlike SARS-CoV, SARS-CoV-2 can also infect the upper respiratory tract which boosts transmissibility
• What is the incubation period & 3 stages of whooping cough?

  Incubation period: 4-21 days

  
  

  1st stage: Catarrhal stage, 1-2 weeks

  2nd stage: Paroxysmal stage, 1-6 weeks

  3rd stage: Covalescent stage, weeks-months

  
• What are the symptoms of COVID-19?

  
• What is whooping cough caused by?

  Bordetella pertussis -aerobic, gram negative coccobacillus

  (bacterial infections of the respiratory tract)

  
• Which family doesBordetella pertussis belong to?

  Alcaligenaceae family