LT 10 The Respiratory System

Question 1

Upper respiratory tract structure

Answer 1

The upper respiratory tract (URT) the nose,
nasal cavities, sinuses, pharynx and larynx

Functions:

Primarily responsible for air movement, not gas exchange.
Contains robust epithelial surfaces to protect against pathogens.
Has the highest exposure to inhaled particles, with large particles often deposited here.

Common Causes of URT Infections:

Viral: Very common (e.g., rhinovirus, RSV, influenzavirus).
Bacterial: Common (e.g., Bordetella pertussis, Streptococcus pyogenes).
Fungal: Rare, usually in immunocompromised individuals.
Typical Symptoms:

Rhinitis: Inflammation of the nose.
Pharyngitis: Inflammation of the throat

Question 2

What are the key features, functions, and common infections associated with the lower respiratory tract (LRT)?

Answer 2

Structures: Includes the trachea, primary bronchi, and lungs.

Functions:

Air-movement: Conducted by the trachea and bronchi, aided by a mucociliary blanket.
Gas exchange: Occurs in the alveoli, where the epithelium is thin but at high risk.
Exposure: Farthest from the environment, mostly exposed to small particles.
Common Causes of LRT Infections:

Viral: Common (e.g., influenzavirus).
Bacterial: Common (e.g., TB, Streptococcus pneumoniae, Legionella).
Fungal: Rare, usually in immunocompromised individuals (e.g., Aspergillus, Histoplasma).
Typical Symptoms:

Pneumonia: Inflammation of the lungs’ air sacs.
Granuloma: Formation of immune cell aggregates

Question 2

How do microbial exposures differ between the upper and lower respiratory tracts?

Answer 2

Upper Respiratory Tract (URT):

Has a resident microbiota and high exposure to microbes.
Transient infections are common due to frequent microbial encounters.

Lower Respiratory Tract (LRT):

LRT has a large surface area with different environmental conditions.
Lacks a normal resident microbiota, leading to chronic infections when exposed

Question 3

What are the primary functions of the respiratory system, and what health risks are associated with them?

Answer 3

Primary Function:

Air movement to facilitate gas exchange and vocalization.

Health Risks:

Large air volume moved in and out exposes the system to airborne particles.
Thin epithelial surfaces in the lungs increase the risk of infection and damage.
Respiratory actions generate particles that can spread infections, with high risk for both entry and transmission of pathogens.

Question 4

hat is the average microbial exposure for an adult, and how does it vary by environment?

Answer 4

Average Adult Inhales:

~8 liters of air per minute (about 11,500 liters per day).
Air contains ~510,000 bacteria and ~450,000 virions per cubic meter.
This results in inhaling around 1 million microbes each day.

Environmental Variation:

Microbe load is typically higher in outdoor environments than indoors (filtered air).
The size and source of particles containing microbes also varies, affecting exposure levels

Question 5

How do microbes cause damage to the respiratory system, and what mechanisms lead to pathology?

Answer 5

Colonization: Microbes naturally colonize exposed mucosal surfaces.
Defense Mechanisms: The respiratory system has multiple defenses to prevent infection.
Pathology Mechanisms:
Toxicological: Pathogen secretes molecules (e.g., pertussis toxin) that damage host cells.
Immunological: Pathogen triggers an immune response that damages host cells (e.g., inflammation).
Cytopathic: Pathogen growth causes host cells to trigger death pathways (e.g., necroptosis).
Key Point: Most pathology requires the pathogen to be close to or in contact with host epithelial cells.

Question 6

What role does mucus play in defending the respiratory system against microbes?

Answer 6

Mucus as a Barrier:
Limits microbe contact with epithelial cells.
Contains antibacterial enzymes (e.g., lysozyme) that degrade bacterial cell walls.
Limits essential nutrients by secreting lactoferrin to reduce iron availability.
Contains other antimicrobial chemicals (e.g., cationic peptides).
Immune Support: Mucus permits the immigration of phagocytic immune cells like neutrophils to fight infection.

Question 7

What is the function of the mucociliary blanket in the lower respiratory system?

Answer 7

Mucociliary Blanket:
Coats the airways of the lower respiratory system.
Ciliary Action: Moves trapped particles (including microbes) towards the mouth, where they are swallowed and neutralized.

Question 8

What are the categories of bacterial and fungal pathogens affecting the respiratory system?

Answer 8

Specialist Pathogens: Streptococcus pyogenes, Mycobacterium tuberculosis.
Opportunistic Commensals: Streptococcus pneumoniae, Candida.
Environmental Opportunists: Aspergillus, Histoplasma, Legionella.

Question 9

What are the key characteristics and species of Streptococcus that impact human health?

Answer 9

Key Species:
Streptococcus pneumoniae (AKA Pneumococcus): Common cause of pneumonia, it can cause pneumonia when the immune system is compromised.
Streptococcus pyogenes (AKA Group A Strep, GAS): Causes strep throat and other diseases.
Gram-positive, coccoid cells in chains.
Major causes of mortality and morbidity.

Question 10

What diagnostic tests are historically important for identifying Streptococcus species?

Answer 10

Hemolysis on RBC Agar:
Alpha-hemolytic: Partial lysis (e.g., S. pneumoniae).
Beta-hemolytic: Complete lysis (e.g., S. pyogenes using streptolysin O).
Serotyping (Lancefield groups):
Group A: S. pyogenes.
Group B: S. agalactiae (not a respiratory pathogen).
Non-groupable: S. pneumoniae.

Question 11

What are the key facts about Streptococcus pneumoniae (Pneumococcus) and its impact on human health?

Answer 11

Leading Cause of Infectious Disease Death:
Historically, 95% of pneumonia cases; still ~25% globally.
High Carriage Rates:
~25% in healthy adults, ~50% in healthy children.
Lower carriage in vaccinated populations.
Most Affected:
Infants, elderly, and those with impaired lung function or influenza.
Treatment: Antibiotics; outcome depends on co-morbidities.

Question 12

Describe the pathogenesis of pneumococcal pneumonia.

Answer 12

Colonization: Begins in the upper respiratory tract (URT).
Invasion: Continuous aerosol exposure leads to lung invasion.
Infection: Triggered by impaired inflammation regulation or lung function.
Immune Response: Involves neutrophils, cytokines, and antibodies.

Question 13

What are the diseases caused by Streptococcus pyogenes (Group A Strep, GAS) and its transmission methods?

Answer 13

Diseases:
Pharyngitis, rheumatic heart disease (RHD), impetigo, necrotizing fasciitis.
Global Impact: ~33 million cases and ~600,000 deaths annually.
Transmission: Via aerosol or direct contact (wounds).

Question 14

What are the clinical presentations of Streptococcus pyogenes infection?

Answer 14

URT Disease: Pharyngitis (strep throat), which can lead to:
Scarlet fever.
Rheumatic fever/heart disease.
Glomerulonephritis.

Non-URT Infections: Impetigo, necrotizing fasciitis.

Clinical Variability: Different strains cause different outcomes.

Question 15

What are the key virulence factors of Streptococcus pyogenes?

Answer 15

Attachment: M protein (encoded by emm gene) promotes attachment to host cells.
Immune Evasion: Enzymes degrade IgG and DNA, capsule provides a protective cloak.
Immune Damage: Superantigens (e.g., SpeA, SpeC) accelerate T-cell signaling.massive, uncontrolled T-cell activation, leading to the release of large amounts of cytokines (a “cytokine storm”).
=> causes widespread inflammation, tissue damage, and sometimes leads to toxic shock syndrome (TSS), which can be life-threatening.

Question 16

What are the key genome-based insights into Streptococcus pathogens?

Answer 16

Genome Size: 2 Mb (~2000 genes).
Core Genes: ~1300 (present in all strains).
Accessory Genes: ~6000, contributing to diversity.

Geographic Patterns:
- Low-Income, Rural Tropics:
High prevalence in endemic regions.
High diversity with no dominant emm types.
- High-Income, Temperate Climates:
Outbreaks often involve dominant emm types.
- Unique Lineages: Specific to Oceania (mainly Australia).

Question 17

What is the significance of a human-restricted pathogenic lifestyle for Streptococcus?

Answer 17

Spread Necessity: Pathogens need to spread to survive.
Carriage Patterns:
- Asymptomatic Throat Carriage: Common, with high point prevalence.
- Long-Term Throat Carriage: Rare.
- Serotypes Shared: Some serotypes are shared between impetigo and throat carriage.
Outbreak Example: Outbreak of emm-55 shows the importance of monitoring serotype shifts.

Question 18

What are the key features of Mycobacterium tuberculosis (Mtb) and its diagnostic challenges?

Answer 18

Genus Mycobacterium: Slow-growing with a distinctive hydrophobic cell wall.

Diagnostic Challenges:
Gram Stain: Ineffective; use Ziehl–Nielsen (Acid-fast) stain instead.
Culture-based Tests: Slow for both diagnosis and antibiotic sensitivity.

Waxy Cell Wall:
Makes cells resistant to phagocytic clearance.
Allows growth inside macrophages.

Key Feature: Mycolic acids in the cell wall.

Question 18

emm meaning

Answer 18

a gene in Streptococcus pyogenes (Group A Streptococcus, or GAS) that encodes the M protein, a major virulence factor of this bacterium.

Question 18

How can Streptococcus pyogenes infections be prevented and treated?

Answer 18

Prevention:
Effective hygiene practices (handwashing, covering coughs, wound care).
Quarantine infected individuals (e.g., with Scarlet fever).

Carriers: Asymptomatic carriers are not considered a major risk.

Vaccination: No vaccines are available.

Treatment:
Antibiotics: Usually effective (e.g., β-lactams like penicillin, cephalosporin).

Outcome: Reduces severity of pharyngitis and complications.

Question 18

What are the key characteristics of Tuberculosis (TB) caused by Mycobacterium tuberculosis?

Answer 18

Active Disease: The number one infectious disease source of morbidity and mortality.

Transmission: Airborne, typically after prolonged exposure to someone with active TB.

Chronic Latent Infection:
Persistent and can be lifelong.
No risk of transmission during latency, but re-activation can occur.

Human Host: The only natural reservoir, though reverse zoonoses are reported.

Note: TB can also be caused by other species like Mycobacterium bovis.

Question 19

What are the key virulence mechanisms of Mycobacterium tuberculosis?

Answer 19

Highly Adapted Pathogen:

Mycolic Acid: Waxy, hydrophobic properties protect Mtb against immune attacks.
ESX-1 : phagosome membrane rupture
ESX-3 : hinders phagosome maturation
Hip 1 gene: impair cytokine production, maturation of dendritic cells and their antigen presentation and dampen T cell response

Question 20

How does Tuberculosis (TB) progress through different stages in humans?

Answer 20

Mtb as a ‘Good Pathogen’:
Causes mild respiratory symptoms.
Most infections are cleared or progress to latency (incipient TB).
Not Contagious in this stage.

Mtb as a ‘Major Killer’:
Can disseminate from lungs to other body parts.
Causes severe lung damage and death.
Infectious in this stage.

Question 21

What are the strategies for preventing and treating Tuberculosis (TB)?

Answer 21

Prevention:
Early diagnosis and quarantine are critical to preventing spread.
BCG Vaccine: Developed over 100 years ago, still in use in endemic areas.
Treatment:
Requires a combination of drugs taken for 6 to 9 months if the bacteria are drug-sensitive.
Challenge: Many Mtb strains have developed resistance to the antimicrobial drugs used to treat TB, leading to MDR (multi-drug-resistant) and XDR (extensively drug-resistant) strains.

Question 22

Front: What are fungi and how are they different from bacteria?

Answer 22

Back: Fungi are eukaryotic organisms with cell structures and functions more similar to human cells. They differ fundamentally from bacteria, making antibacterial drugs ineffective against them. Developing safe, specific antifungal drugs is challenging.

Question 23

Front: What is a fungal infection called, and how do fungi typically spread?

Answer 23

Back: A fungal infection is termed a mycosis. Many fungi reproduce and disperse via small spores (2-20 µm) that are aerodynamically spread and easily inhaled.

Question 24

Front: Which individuals are at higher risk for opportunistic fungal infections of the respiratory tract?

Answer 24

Back: Those at higher risk include the immuno-suppressed (e.g., chemotherapy, AIDS), the very young or elderly, and individuals highly exposed to spores.

Question 25

Front: Where is Aspergillus fumigatus commonly found, and why is it a concern?

Answer 25

Back: Aspergillus fumigatus is a spore-forming fungus found in moist, organic-rich environments like garden soil and compost heaps. It can grow at 37°C and is a concern due to its ability to cause infection in immunocompromised individuals.

Question 26

Front: What is Aspergillosis, and who is most at risk?

Answer 26

Back: Aspergillosis, including Farmer’s Lung, is an infection caused by inhalation of Aspergillus fumigatus spores. It primarily affects individuals who are immunocompromised or have high exposure to the spores.

Question 27

Front: How does Aspergillus fumigatus infect susceptible individuals?

Answer 27

Back: In susceptible individuals, A. fumigatus spores can attach to and enter alveolar cells, germinate, escape into tissues, and disseminate via the bloodstream.

Question 28

Front: How does the severity of Aspergillosis vary, and what are some potential complications?

Answer 28

Back: The severity of Aspergillosis increases with the level of host immunocompromise. Complications can include the formation of an Aspergilloma (fungal ball) in the lungs and dissemination to other organs, such as the brain.

Question 29

Front: What are the challenges and treatments associated with Aspergillosis?

Answer 29

Back: Aspergillosis is treated with antifungal drugs (e.g., Azoles), which target fungal cell membranes. Challenges include the selectivity of antifungals due to the similarity of fungal cells to human cells. Significant side effects may occur, and surgical resection may be required for cavitary Aspergilloma.