Microbial Infectious Diseases of the Respiratory System

Overview of Respiratory System Microbiology

The respiratory system is a complex network of tissues and organs that is constantly exposed to airborne microorganisms. While many microbes colonize the respiratory tract, only a subset are pathogenic and capable of causing disease. This section introduces the major infectious diseases affecting the respiratory system, focusing on strep throat, tuberculosis, and influenza.

• High microbial diversity exists within and among respiratory tissues/organs.

• Most microbes are not pathogens.

• Approximately 33% of healthy individuals carry Staphylococcus aureus in the nose (potential opportunist).

• Many organisms colonize the upper throat.

Chemical and Mechanical Defenses of the Respiratory System

The respiratory system employs several defense mechanisms to prevent infection:

• Lymphoid tissues (tonsils, adenoids) contain B and T lymphocytes for immune surveillance.

• Mucus contains antimicrobial substances: dermicidins, lactoferrin, lysozyme, and secretory IgA.

• Ciliated mucous membranes line the trachea, bronchi, and bronchioles, helping to trap and expel pathogens.

Streptococcal Respiratory Diseases (Strep Throat and Scarlet Fever)

Streptococcus pyogenes: Pathogen and Virulence Factors

Streptococcus pyogenes is the primary cause of strep throat (bacterial pharyngitis). It is a Gram-positive, beta-hemolytic bacterium with several virulence factors:

• Capsule with M protein and hyaluronic acid: resists phagocytosis.

• Streptolysins: lyse blood cells.

• Streptokinases: lyse blood clots.

• Pyrogenic toxins: stimulate leukocytes to release cytokines, causing fever, rash, and shock.

• Lancefield groupings based on teichoic acid antigens; Group A strep is caused by S. pyogenes.

Signs and Symptoms of Streptococcal Respiratory Diseases

• Redness at the back of the pharynx

• Swollen lymph nodes

• Purulent abscesses over tonsils

• Pain during swallowing

• Fever, malaise, headache

• Bacteria can spread to larynx and bronchi, causing laryngitis and bronchitis

Scarlet Fever (Scarlatina)

Scarlet fever can develop if S. pyogenes is infected with a lysogenic phage encoding pyrogenic toxins.

• Occurs after 1-2 days of pharyngitis

• Toxins trigger fever and a diffuse rash that begins on the chest and spreads

• Tongue becomes strawberry red

• Rash disappears after about one week; skin sloughs off

Epidemiology

• Spread via respiratory droplets

• Most common in winter and spring among children ages 5-15

• Humans are the only reservoir

Treatment and Prevention

• Antibiotics: Oral or intramuscular penicillin G, penicillin V, or amoxicillin

• Antibodies against M protein provide long-term protection (more than 50 kinds of M proteins exist)

• Antibiotic intervention often precludes development of protective antibodies

Tuberculosis

Pathogen and Virulence Factors

Mycobacterium tuberculosis is a Gram-positive rod with unique features:

• Mycolic acid in cell wall (acid-fast positive)

• Very slow growth

• Protected from destruction following phagocytosis (intracellular growth)

• Resistant to Gram staining, detergents, many common antimicrobial drugs, and desiccation

• Cord factor: prevents fusion of phagosomes with lysosomes, allowing bacteria to evade phagocytosis

Pathogenesis: Granuloma Formation

• Macrophages in alveoli phagocytize organisms but cannot digest them

• Bacteria replicate within macrophages, gradually killing them

• T cells produce lymphokines that attract and activate more macrophages, triggering inflammation

• Collagen fibers enclose granuloma

• Immune system reaches stalemate with Mycobacterium

Secondary (Reactivated) Tuberculosis

• Occurs when bacteria break out of the granuloma

• Organisms rupture tubercle and reestablish active infection ("consumption")

• Bacteria spread through lungs via bronchioles

• Occurs in about 10% of patients

Treatment and Prevention

• Some strains are multidrug resistant (MDR) or extremely drug resistant (XDR)

• Bedaquiline: antibiotic that targets ATP synthase in Mycobacterium

• BCG vaccine (live, attenuated): not recommended for adults, low efficacy; not widely used in the U.S. due to low prevalence

Influenza

Pathogens and Virulence Factors

Influenza is caused by orthomyxoviruses, primarily types A and B.

• Structure: Eight different ssRNA molecules as genome

• Glycoprotein spike variation:

  • Neuraminidase: hydrolyzes mucus in lungs, allowing virus to spread

  • Hemagglutinin: binds to pulmonary epithelial cells and triggers endocytosis

• Infects lung epithelial cells in upper and lower respiratory tract

Antigenic Drift and Shift

• Antigenic drift: 1 virus enters the host and mutates, producing new strains with slight differences

• Antigenic shift: 2 viruses enter the host, genomes reassort, and a brand new virus hybrid exits the cell

Historical Example: 1918 H1N1 Pandemic (Spanish Flu)

• Reduced average life expectancy by 12+ years

• Killed 50 million people worldwide

• Novel virus arose through antigenic shift (mammal + avian virus reassortment)

• H1N1 has undergone antigenic drift since 1918 and now has different protein features

Pathogenesis, Signs and Symptoms, and Treatment

Key Terms and Concepts

• Beta-hemolytic: Bacteria that completely lyse red blood cells on blood agar

• Pharyngitis: Inflammation of the pharynx, causing sore throat

• Granuloma: A mass of immune cells formed to wall off persistent pathogens

• Antigenic drift/shift: Mechanisms by which influenza viruses change their surface proteins, leading to new strains

Formulas and Equations

• Antigenic Shift (Reassortment):

• Antibiotic Mechanism (Bedaquiline):

Additional info: These notes expand on the original slides by providing definitions, context, and structured comparisons for exam preparation.