🫀🫁Cardio & Resp🫀🫁 - Respiratory Tract Infections & Immunity

Question 1

What are the 3 categories of respiratory infection?

Answer 1

Upper respiratory tract infection
Lower respiratory tract infection
Pneumonia

Question 2

What are the symptoms of an upper respiratory tract infection?

Answer 2

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

Question 3

What are the symptoms of a lower respiratory tract infection?

Answer 3

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

Question 4

What are the symptoms of pneumonia?

Answer 4

Chest pain
Blue tinting of the lips
Severe fatigue
High Fever

Question 5

What are the categories for general risk factors for pneumonia?

Answer 5

Demographic/lifestyle factors
Social factors
Medications
Medical history

Question 6

What demographic/lifestyle factors would put someone at increased risk for pneumonia?

Answer 6

Age <2 or >65 years
Cigarette smoking
Excess alcohol consumption

Question 7

What social factors predispose someone to pneumonia?

Answer 7

Contact with children aged <15 years (e.g. teachers, parents)
Poverty
Overcrowding

Question 8

What medications puts someone more at risk of developing pneumonia?

Answer 8

Inhaled corticosteroids
Immunosuppressants (e.g. steroids)
Proton pump inhibitors

Question 9

What previous medical history leaves someone more at risk of developing pneumonia?

Answer 9

COPD, asthma
Heart disease
Diabetes mellitus, HIV and Immunoglobulin (Ig) deficiencies (immunocompromised)
Risk factors for aspiration (e.g. dysphagia)
(Others include liver disease, malignancy, hypersplenism, complement deficiencies, previous pneumonia)

Question 10

Outline asthma as a risk factor for pneumonia and hospitalisation

Answer 10

Exacerbations – are the most common cause of hospitalization.
Respiratory infections (mostly viral) – are the major cause of exacerbations.
Hospitalization due to exacerbation is a major predictor of asthma mortality
(Severe exacerbations limited to a subset of asthmatics)

Question 11

What are the common causative agents of bacterial respiratory infections?

Answer 11

Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis (less common but clinically relevant)

Question 12

What are the common causative agents of viral respiratory infections?

Answer 12

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

Question 13

What are the different types of airway inflammation?

Answer 13

Bronchitis- Inflammation and swelling of the bronchi
Bronchiolitis - Inflammation and swelling of the bronchioles
Pneumonia - Inflammation and swelling of the alveoli

Question 14

What are the mechanisms of damage of pneumonia?

Answer 14

Pneumonia can cause lung injury, leading to arterial hypoxemia and possibly progressing to ARDS
Bacteraemia (bacteria in the bloodstream from an infection) can cause organ infection and subsequent organ injury or dysfunction, which may lead to sepsis
Systemic inflammation affects various systems, disrupting immunity, the endothelium, the microbiome, coagulation, and the autonomic nervous system
These disruptions contribute to overall deterioration in multiple body functions, including pulmonary, cardiovascular, hematologic, cognitive, and psychological systems

Question 15

How is potential bacterial pneumonia graded?

Answer 15

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 - greater than 7 mmol/L

Question 16

What are the common causes of community acquired pneumonia (CAP)?

Answer 16

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

Question 17

What is Streptococcus pneumoniae?

Answer 17

Gram-positive, extracellular, opportunistic pathogen

Question 18

How can pneumonia be acquire in hospital?

Answer 18

Hospital acquired pneumonia
(Staphylococcus aureus
Psuedomonas aeruginosa
Klebsiella species
E. coli
Acinetobacter spp.
Enterobacter spp.)
Ventilator associated pneumonia
(Pseudomonas aeruginosa (25%)
Staphylococcus aureus(20%)
Enterobacter)

Question 19

What are typical vs atypic pneumonias?

Answer 19

Atypical pneumonias present with slightly different symptoms (some with longer milder symptoms for instance)
Atypical pneumonias are often more difficult to culture (hence atypical - may require a different antibiotic regime
Penicillins often given for typical pneumonia, additional macrolides may be administered for atypical

Question 20

Outline typical pneumonia

Answer 20

Most common type
Caused by most common forms of bacteria

Question 21

Outline atypical pneumonia

Answer 21

Less frequent
Distinct bacterial species
e.g. M. pneumoniae is a simple gram negative bacteria
Slower onset of symptoms and milder
= ”walking pneumonia”

Question 22

What are the treatments for bacterial pneumonia?

Answer 22

Supportive therapy
-Oxygen (for hypoxia)
-Fluids (for dehydration)
-Analgesia (for pain)
Antibiotics
-Penicillins e.g. amoxicillin - beta lactams
-Macrolides e.g. clarithromycin - bind to bacterial ribosomes

Question 23

Where can bacterial pneumonia originate?

Answer 23

Oropharynx
-Haemophilus spp.
-Staph. aureus
-Strep. pneumoniae
Nose
-Staph. aureus
-Strep, pneumoniae

Question 24

What is the most common cause of bacterial respiratory tract infection?

Answer 24

Diverse causes but streptococcus pneumoniae is the most common
Often a result of movement of microbes into the lower lungs from other sites

Question 25

Why do viral respiratory infections have widely varying outcomes?

Answer 25

Dependant on host response Host response can be optimal or lead to physiological detriment

Question 26

What would constitute a detrimental host response to a viral infection in the lungs?

Answer 26

Airway narrowing Fluid and mucus build-up in the airways and parenchyma Damage to the gas exchange surfaces (essentially what is seen in ARDS)

Question 27

How does SARS-CoV-2 infect the body?

Answer 27

Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2) High ACE2 in nasal epithelium and type 2 pneumocytes (especially in smokers)

Question 28

Where does H1N1 influenza A infect via?

Answer 28

Haemagglutinin binds 𝛂2,6 sialic acids

Question 29

Where does H5N1 avian flu infect via?

Answer 29

Haemagglutinin binds 𝛂2,3 sialic acids

Question 30

Where does the "common cold" (i.e. rhinoviruses) infect via?

Answer 30

Major group – ICAM-1 Minor group – LDLR

Question 31

What is the main form of airway infection in infants?

Answer 31

RSV - cause bronchiolitis in infants 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

Question 32

What are the risk factors for RSV in infants?

Answer 32

Premature birth Congenital heart and lung disease

Question 33

What are the host defences against respiratory tract infection?

Answer 33

Physical Barriers of the upper airway -Hairs and cilia – particulate capture Physical and chemical barriers of the epithelial lumen -Fluid lining the lumen -Mucociliary escalator -Epithelial barrier Immune fortification -Innate immune responses -Resident immune cells -Recruited immune cells

Question 34

What defences does the respiratory epithelium have against infection?

Answer 34

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

Question 35

What is the role of type 1 interferons (IFN-1) in viral infections?

Answer 35

Rapid Activation: Upon viral infection, cellular receptors recognize viral components and quickly activate IFN-I production within hours, initiating a fast immune response Antiviral State: IFN-I binds to receptors on infected and nearby cells, activating genes that: -Block viral entry and replication -Inhibit viral assembly and release, reducing viral spread Enhanced Immune Response: IFN-I boosts the immune system by: -Activating NK cells to kill infected cells -Increasing antigen presentation to help T cells recognize infected cells -Stimulating dendritic cells and macrophages, linking innate and adaptive immunity Adaptive Immune Activation: IFN-I aids in activating T cells and B cells

Question 36

What are the innate immune defences in alveoli against respiratory infections?

Answer 36

Alveolar macrophages - phagocytosis, tissue homeostasis and pathogen sensing Resident dendritic cells - respond to inflammation and act as APCs Neutrophils - main cell type recruited early. Some antiviral immunity but can also result in inflammatory damage Natural Killer cells - innate anti-viral immunity against infected cells Monocytes - recruited into the site and provide mediators and a source of macrophages

Question 37

Outline the adaptive immune response to respiratory tract infections

Answer 37

Take a week or more to develop after a first infection CD8 T cells provide antigen specific cytotoxic immunity and immunological memory (both resident and systemic) B cells differentiate into antigen specific antibody secreting cells and memory B cells. Providing neutralizing immunity

Question 38

What are serotypes, and why are they important in viral immunity?

Answer 38

Serotypes are distinct forms of pathogens not recognized by antibodies targeting other pathogens. They help us understand immune system diversity and the need for varied immune responses

Question 39

Where is IgA most active in the respiratory tract, and what is its role?

Answer 39

IgA is concentrated in the upper respiratory tract (nasal cavity and pharynx), where it is transported to the mucosal surface Homodimer form is extremely stable in protease-rich areas, protecting mucosal surfaces and making it ideal for such environments

Question 40

How does IgG function in the respiratory tract, and where is it most important?

Answer 40

IgG is predominant in the lower respiratory tract, especially in the alveolar space Thin-walled environment allows IgG to transfer easily, providing immunity deep in the lungs

Question 41

What is the relationship between rhinovirus serotypes and viral immunity?

Answer 41

100-300+ different serotypes within RV-A, B and C strains Long lasting antibody mediated immunity

Question 42

What is the relationship between influenza serotypes and viral immunity?

Answer 42

No re-infection by same strain Influenza strains ”drift” and ”shift” surface antigens (HA, N) to avoid antibody mediated immunity

Question 43

What is the relationship between RSV serotypes and viral immunity?

Answer 43

Recurrent infection with the same serotype/strain Limited mutation of surface antigens. (F, G) Natural antibodies wane rapidly allowing re-infection

Question 44

What is the relationship between SARS-CoV-2 serotypes and viral immunity?

Answer 44

Antigenically novel coronavirus No prior exposure Antibodies wane over time Some evidence of surface antigen mutation

Question 45

What are the treatment options for respiratory tract infections?

Answer 45

Supportive therapy Preventative/prophylactic -Vaccines - only work before or between infections Therapeutic -Anti-inflammatory - pathology specific (e.g. dexamethasone) Anti-virals - timing essential