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Cardiovascular & Respiratory Medicine > Respiratory tract infections and immunity > Flashcards

Respiratory tract infections and immunity Flashcards

1
Q

What are the signs and symptoms of an upper respiratory tract infection?

A

A cough
Sneezing
A runny or stuffy nose
A sore throat
Headache

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2
Q

What are the signs and symptoms of lower respiratory tract infection?

A

A “productive” cough - phlegm
Muscle aches
Wheezing
Breathlessness
Fever
Fatigue

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3
Q

What are the signs and symptoms of pneumonia?

A

Chest pain
Blue tinting of the lips
Severe fatigue
High Fever

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4
Q

What is “DALY”?

A

“Disability- adjusted Life Year”=
A sum of years of life lost (YLL) and years lost to disability (YLP)

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5
Q

Age dramatically impacts mortality burden, true or false?

A

TRUE

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6
Q

Pneumonia rates increase with age, true or false?

A

TRUE

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7
Q

A mix of viral and bacterial causes, can lead to respiratory illness true or false?

A

TRUE: there is no single dominant pathogen, there can be copathogens: bacteria-bacteria, virus-virus or virus- bacteria

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8
Q

List the demographic and lifestyle risk factors for Pneumonia?

A

Demographic and lifestyle factors:
Age <2 years or >65 years
Cigarette smoking
Excess alcohol consumption

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9
Q

List the social risk factors for Pneumonia?

A

Social factors:
Contact with children aged <15 years
Poverty
Overcrowding

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10
Q

List the medical risk factors for Pneumonia?

A

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

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11
Q

List risk factors for certain pathogens, causing pneumonia

A

Geographical variations
Animal contact
Healthcare contacts

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12
Q

What are the common causative agents for respiratory infection?

A

Bacterial:
Streptococcus pneumoniae
Myxoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis

Viral:
Influenza A or B virus
Respiratory Syncytial Virus
Human metapneumovirus
Human rhinovirus
Coronaviruses

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13
Q

Give examples of bacteria that cause community acquired pneumonia (CAP):

A

Streptococcus pneumoniae (40-50%)
Myxoplasma pneumoniae
Staphylococcus aureus
Chlamydia pneumoniae
Haemophilus Influenzae

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14
Q

Give examples of the most common/ typical bacteria for pneumonia

A

Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis

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15
Q

Give examples of hospital acquired pneumonia

A

Staphylococcus aureus
Psuedomonas aeruginosa
Klebsiella species
E. coli
Acinetobacter spp.
Enterobacter spp.

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16
Q

Give examples of ventilator acquired pneumonia

A

Psuedomonas aeruginosa (25%)
Staphylococcus aureus(20%)
Enterobacter

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17
Q

give examples of atypical bacteria associated with pneumonia

A

Mycoplasma pneumoniae, Chlamydia pneumoniae,
Legionella pneumophilia

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18
Q

Describe streptococcus pneumoniae

A

Gram- positive
Extracellular
Opportunistic pathogen

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19
Q

What are the consequences of bacterial infections in the lower airways?

A

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

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20
Q

What other issues can result from pneumonia?

A
  1. Lung injury -> arterial hypoxemia -> ARDS/ organ injury or dysfunction (Sepsis/ Deterioration)
  2. Bacteremia -> organ infection -> organ injury or dysfunction (Sepsis or deterioration) / overactive immune response (deterioration)
  3. Systemic inflammation -> overactive immune response (deterioration/ organ injury or dysfunction (sepsis)
    Treatment -> overactive immune response (organ injury or dysfunction, sepsis, deterioration)
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21
Q

What is the process of Grading potential bacterial pneumonia?

A

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

22
Q

How is bacterial pneumonia treated?

A

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

23
Q

What is the key to increasing the success of antibiotics?

A
  1. Combining (if severe)
  2. Time of administration
24
Q

What is the human microbiome?

A

100 trillion microbial cells populate our bodies at every barrier surface

25
Q

What is meant by “microbiota”?

A

Ecological communities of microbes found inside multi-cellular organisms

26
Q

What is commensal bacteria?

A

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

27
Q

Can you catch penumonia?

A

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.

28
Q

What are opportunistic pathogens?

A

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

29
Q

What are Pathobiont bacteria?

A

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

30
Q

Why do viral infections result in disease?

A

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)

31
Q

What causes severe disease?

A
  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
32
Q

What is meant by viral load?

A

How much a virus can replicate

33
Q

Where does H1N1 influenza A virus infect?

A

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

34
Q

Where does H5N1 avian flu infect?

A

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

35
Q

Where does the SARS-CoV-2 virus infect?

A

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

36
Q

Why does SARS-Cov-2 affect smokers more severly?

A

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

37
Q

What is the significance of virus binding?

A

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.

38
Q

What is the role of different epithelial cells in immunity?

A
  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.
39
Q

What is meant by the term “serotypes”?

A

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

40
Q

What is an antigen?

A

any molecule against which antibodies can be generated.

41
Q

Describe the mechanism of action of antibody mediated immunity

A
  • 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
42
Q

What antibodies are most found in the nasal cavity?

A

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

43
Q

What antibodies are most found in the bronchi?

A

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

44
Q

Describe the strains of and our immunity against Influenza virus

A

No re-infection by same strain

Imperfect vaccines:
Vaccine-induced immunity rapidly wanes (changes)
Mainly homotypic immunity
Annual vaccination required

45
Q

Describe the strains of and our immunity against the Respiratory Syncytial virus (RSV)

A

Recurrent re-infection with similar strains

No vaccine
Poor immunogenicity
Vaccine-enhanced disease
Very active research field

46
Q

Describe the strains of and our immunity against the SARS-Cov-2 virus

A

No prior immunity

Newly licenced vaccine
Waning immunity
Potential for re-infection
Unclear what vaccination regime will be required

47
Q

Compare influenza with RSV

A

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

48
Q

How does RSV bronchiolitis affect infants?

A
  • 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
49
Q

What are risk factors of infants developing RSV bronchiolitis?

A
  • Premature birth
  • Congenital heart and lung disease
50
Q

What are treatment options against viruses?

A

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

51
Q

How can resp infections/ virus affect chronic lung diseases?

A
  • 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

Cardiovascular & Respiratory Medicine (14 decks)

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