Respiratory tract infections and immunity Flashcards

Question

What is meant by "microbiota"?

Answer 1

Ecological communities of microbes found inside multi-cellular organisms

Answer 2

Microbes that live in a “symbiotic” relationship with their host. Providing vital nutrients to the host in the presence of a suitable ecological niche.

Answer 3

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.

Answer 4

Opportunistic Pathogen: A microbe that takes advantage of a change in conditions (often immuno -suppression).

Answer 5

Pathobiont: A microbe that is normally commensal, but if found in the wrong environment (e.g. anatomical site) can cause pathology.

Answer 6

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)

Answer 7

1. Highly pathogenic strains (zoonotic- come from animals, and replicates in humans) 2. Absence of prior immunity * Innate immunodeficiency (e.g. IFITM3 gene variant) * B cells (antibody- presumably local) * T cells (correlate with peripheral levels?) 3. Predisposing illness/conditions * Frail elderly * COPD/asthma * Diabetes, obesity, pregnancy etc

Answer 8

How much a virus can replicate

Answer 9

Haemogglutinin binds alpha2,6 sialic acids (found in the upper resp tract)

Answer 10

Haemogglutinin binds alpha2,3 sialic acids (found in the lower resp tract)

Answer 11

Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2) [high ACE2 in nasal epithelium and type 2 pneumocytes in the lungs]

Answer 12

The virus spike (S) proteins bind to Angiotensin converting enzyme 2 (ACE2)- smokers have more of these receptors

Answer 13

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.

Answer 14

1. Tight junctions – prevents systemic infection 2. Mucous lining and cilial clearance – prevents attachment, clears particulates 3. Antimicrobials – recognise, neutralise and/or degrade microbes and their products 4. Pathogen recognition receptors – recognise pathogens either outside or inside a cell 5. Interferon pathways – activated by viral infection. Promotes upregulation of anti-viral proteins and apoptosis.

Answer 15

Serotypes: viruses which cannot be recognised by serum (really antibodies) that recognise another virus – implications for protective immunity

Answer 16

any molecule against which antibodies can be generated.

Answer 17

- 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

Answer 18

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

Answer 19

IgG: Thin-walled alveolar space allows transfer of plasma IgGs into the alveolar space

Answer 20

No re-infection by same strain Imperfect vaccines: Vaccine-induced immunity rapidly wanes (changes) Mainly homotypic immunity Annual vaccination required

Answer 21

Recurrent re-infection with similar strains No vaccine Poor immunogenicity Vaccine-enhanced disease Very active research field

Answer 22

No prior immunity Newly licenced vaccine Waning immunity Potential for re-infection Unclear what vaccination regime will be required

Answer 23

Influenza: - Replicates faster (correlates with viral load- replication peaks earlier) - peaks at day 5 of infection RSV: - slower - peaks at day 6/7

Answer 24

- 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

Answer 25

- Premature birth - Congenital heart and lung disease

Answer 26

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

Answer 27

- 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