🫀🫁Cardio & Resp🫀🫁 - Respiratory Tract Infections & Immunity Flashcards
What are the 3 categories of respiratory infection?
Upper respiratory tract infection
Lower respiratory tract infection
Pneumonia
What are the symptoms of an upper respiratory tract infection?
A cough
Sneezing
A runny or stuffy nose
A sore throat
Headache
What are the symptoms of a lower respiratory tract infection?
A “productive” cough - phlegm
Muscle aches
Wheezing
Breathlessness
Fever
Fatigue
What are the symptoms of pneumonia?
Chest pain
Blue tinting of the lips
Severe fatigue
High Fever
What are the categories for general risk factors for pneumonia?
Demographic/lifestyle factors
Social factors
Medications
Medical history
What demographic/lifestyle factors would put someone at increased risk for pneumonia?
Age <2 or >65 years
Cigarette smoking
Excess alcohol consumption
What social factors predispose someone to pneumonia?
Contact with children aged <15 years (e.g. teachers, parents)
Poverty
Overcrowding
What medications puts someone more at risk of developing pneumonia?
Inhaled corticosteroids
Immunosuppressants (e.g. steroids)
Proton pump inhibitors
What previous medical history leaves someone more at risk of developing pneumonia?
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)
Outline asthma as a risk factor for pneumonia and hospitalisation
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)
What are the common causative agents of bacterial respiratory infections?
Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus Influenzae
Mycobacterium tuberculosis (less common but clinically relevant)
What are the common causative agents of viral respiratory infections?
Influenza A or B virus
Respiratory Syncytial Virus
Human metapneumovirus
Human rhinovirus
Coronaviruses
What are the different types of airway inflammation?
Bronchitis- Inflammation and swelling of the bronchi
Bronchiolitis - Inflammation and swelling of the bronchioles
Pneumonia - Inflammation and swelling of the alveoli
What are the mechanisms of damage of pneumonia?
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
How is potential bacterial pneumonia graded?
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
What are the common causes of community acquired pneumonia (CAP)?
Bacterial
Streptococcus pneumoniae (40-50%)
(Mycoplasma pneumoniae
Staphylococcus aureus
Chlamydia pneumoniae
Haemophilus Influenzae)
What is Streptococcus pneumoniae?
Gram-positive, extracellular, opportunistic pathogen
How can pneumonia be acquire in hospital?
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)
What are typical vs atypic pneumonias?
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
Outline typical pneumonia
Most common type
Caused by most common forms of bacteria
Outline atypical pneumonia
Less frequent
Distinct bacterial species
e.g. M. pneumoniae is a simple gram negative bacteria
Slower onset of symptoms and milder
= ”walking pneumonia”
What are the treatments for bacterial pneumonia?
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
Where can bacterial pneumonia originate?
Oropharynx
-Haemophilus spp.
-Staph. aureus
-Strep. pneumoniae
Nose
-Staph. aureus
-Strep, pneumoniae
What is the most common cause of bacterial respiratory tract infection?
Diverse causes but streptococcus pneumoniae is the most common
Often a result of movement of microbes into the lower lungs from other sites
Why do viral respiratory infections have widely varying outcomes?
Dependant on host response
Host response can be optimal or lead to physiological detriment
What would constitute a detrimental host response to a viral infection in the lungs?
Airway narrowing
Fluid and mucus build-up in the airways and parenchyma
Damage to the gas exchange surfaces
(essentially what is seen in ARDS)
How does SARS-CoV-2 infect the body?
Spike (S) protein binds Angiotensin converting enzyme 2 (ACE2)
High ACE2 in nasal epithelium and type 2 pneumocytes (especially in smokers)
Where does H1N1 influenza A infect via?
Haemagglutinin binds 𝛂2,6 sialic acids
Where does H5N1 avian flu infect via?
Haemagglutinin binds 𝛂2,3 sialic acids
Where does the “common cold” (i.e. rhinoviruses) infect via?
Major group – ICAM-1
Minor group – LDLR
What is the main form of airway infection in infants?
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
What are the risk factors for RSV in infants?
Premature birth
Congenital heart and lung disease
What are the host defences against respiratory tract infection?
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
What defences does the respiratory epithelium have against infection?
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
What is the role of type 1 interferons (IFN-1) in viral infections?
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
What are the innate immune defences in alveoli against respiratory infections?
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
Outline the adaptive immune response to respiratory tract infections
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
What are serotypes, and why are they important in viral immunity?
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
Where is IgA most active in the respiratory tract, and what is its role?
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
How does IgG function in the respiratory tract, and where is it most important?
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
What is the relationship between rhinovirus serotypes and viral immunity?
100-300+ different serotypes within RV-A, B and C strains
Long lasting antibody mediated immunity
What is the relationship between influenza serotypes and viral immunity?
No re-infection by same strain
Influenza strains ”drift” and ”shift” surface antigens (HA, N) to avoid antibody mediated immunity
What is the relationship between RSV serotypes and viral immunity?
Recurrent infection with the same serotype/strain
Limited mutation of surface antigens. (F, G)
Natural antibodies wane rapidly allowing re-infection
What is the relationship between SARS-CoV-2 serotypes and viral immunity?
Antigenically novel coronavirus
No prior exposure
Antibodies wane over time
Some evidence of surface antigen mutation
What are the treatment options for respiratory tract infections?
Supportive therapy
Preventative/prophylactic
-Vaccines - only work before or between infections
Therapeutic
-Anti-inflammatory - pathology specific (e.g. dexamethasone)
Anti-virals - timing essential
