Microbial Diseases of the Respiratory System – Vocabulary Review

Structures of the Upper Respiratory System

• Anatomical components

  • Nose, pharynx, middle ear, eustachian (auditory) tubes

• Innate protection of mucosal surfaces

  • Saliva and tears deliver lysozyme, IgA, defensins, & flushing action

Structures of the Lower Respiratory System

• Organs: larynx, trachea, bronchial tubes, alveoli

• Mechanical & cellular defenses

  • Ciliary escalator moves mucus upward toward pharynx

  • Alveolar macrophages patrol distal airways

  • Respiratory mucus traps microbes & contains antibodies

Normal Microbiota of the Respiratory Tract

• Upper tract harbors potentially pathogenic residents

  • Dominant commensals out-compete newcomers by nutrient depletion & bacteriocin production

• Lower tract is “nearly sterile” in healthy individuals (mucociliary action + phagocytes)

Common Upper-Respiratory Syndromes

• Self-limiting inflammations (usually viral)

  • Pharyngitis (sore throat)

  • Laryngitis

  • Tonsillitis

  • Sinusitis

• Epiglottitis – most life-threatening; airway obstruction risk

Streptococcal Pharyngitis (Strep Throat)

• Etiology: Group A β-hemolytic streptococci – Streptococcus pyogenes

  • Virulence factors

  • Hyaluronic-acid capsule (antiphagocytic)

  • Streptokinases (fibrin lysis)

  • Streptolysins O (oxygen-labile) & S (oxygen-stable) – cytolysins

• Clinical: local throat inflammation, fever, tonsillitis, cervical lymphadenopathy

• Diagnosis: rapid GAS antigen test or throat culture

• Sequela – Scarlet fever

  • Lysogenic conversion → erythrogenic (pyrogenic) toxin → pink rash & “strawberry tongue”

Diphtheria

• Agent: Corynebacterium diphtheriae (Gram +, pleomorphic rod)

• Pathology

  • Tough gray-white pseudomembrane forms in throat → suffocation risk

  • Diphtheria AB exotoxin (lysogen-coded) circulates → myocarditis & nephritis

• Prevention: DTaP vaccine (diphtheria toxoid)

• Therapy: antitoxin + macrolide or penicillin

Otitis Media (Middle-Ear Infection)

• Pus behind tympanic membrane → pressure & pain

• Major agents: Streptococcus pneumoniae, nonencapsulated Haemophilus influenzae, S. pyogenes, respiratory syncytial virus

• Childhood peak (short, horizontal auditory tube)

• Treatment: broad-spectrum penicillins or watchful waiting

The Common Cold

• > 200 distinct viruses

  • Enterovirus (rhinovirus) 30\text{--}50\% – replicate best at <37^\circC (nasal cavity \approx 33^\circC)

  • Betacoronaviruses 10\text{--}15\%

• Symptoms: sneezing, rhinorrhea, congestion; may progress to laryngitis / otitis media; seldom fever

• Pathogenesis

  • Virions bind ICAM-1 on nasal epithelium ("canyon hypothesis": receptor fits into deep groove on capsid, shielding it from antibodies)

• Management: symptomatic (antihistamines, decongestants); antibiotics useless

Overview of Lower-Respiratory Infections

• Bronchitis, bronchiolitis, pneumonia (inflammatory filling of pulmonary alveoli → impaired gas exchange)

Pertussis (Whooping Cough)

• Agent: Bordetella pertussis (Gram - coccobacillus)

• Virulence

  • Polysaccharide capsule mediates attachment to ciliated tracheal cells

  • Tracheal cytotoxin (peptidoglycan fragment) arrests ciliary motion & kills cells

  • Pertussis toxin (AB) enters bloodstream → systemic lymphocytosis, hypoglycemia, etc.

• Clinical stages

  1. Catarrhal (weeks 1): common-cold-like

  2. Paroxysmal (weeks 1\text{--}6): repetitive, violent coughs, inspiratory "whoop"

  3. Convalescent (months): gradual recovery, secondary infections possible

• Prevention: DTaP (acellular pertussis antigens)

• Therapy: macrolides (erythromycin, azithromycin)

Tuberculosis (TB)

• Agent: Mycobacterium tuberculosis

  • Acid-fast, obligate aerobe, slow generation time \approx20 h

  • Mycolic-acid cell wall – resists desiccation & many drugs

• Pathogenesis steps

  1. Inhaled bacilli engulfed by alveolar macrophages; survive intracellularly

  2. Chemotactic influx → early tubercle; cytokine-mediated tissue damage

  3. Macrophage death → caseous center; latent TB bacilli dormant; lesion may calcify (Ghon complex)

  4. Liquefaction enlarges cavity; bacilli replicate extracellularly

  5. Tubercle ruptures → dissemination via bronchi, blood, lymph → miliary TB

• Latent TB: non-contagious, positive skin/IGRA test, normal chest X-ray

Pneumococcal Pneumonia

• Causative bacterium: Streptococcus pneumoniae (Gram +, encapsulated diplococci)

• Symptoms: sudden high fever, pleuritic chest pain, dyspnea; alveoli fill with serous fluid, RBCs, WBCs → rusty sputum

• Virulence factors: capsule (anti-phagocytic), LytA (autolysin), pneumolysin O (pore-forming toxin)

• Prevention: conjugate polysaccharide vaccine (PCV-13; adult PPSV-23)

• Treatment: β-lactams or respiratory fluoroquinolones (resistance rising)

Psittacosis (Ornithosis)

• Agent: Chlamydia psittaci (Gram -, obligate intracellular)

• Reservoir: birds (parrots, pigeons, poultry); inhalation of elementary bodies in dried droppings

• Manifestations: atypical pneumonia with fever, headache, chills, sometimes CNS involvement (disorientation)

• Diagnosis: cell culture in embryonated eggs, PCR assays

• Therapy: tetracyclines; historical mortality 15\text{--}20\% untreated

Influenza (Flu)

• Genome: 8 segmented single-stranded RNA; enveloped Orthomyxovirus

• Clinical triad: chills, fever, myalgia + headache; resolves \approx1 week; secondary bacterial pneumonia common

• Antigenic structures

  • Hemagglutinin (HA) – attaches to sialic-acid receptors on host respiratory epithelium (mediates entry)

  • Neuraminidase (NA) – cleaves sialic acid → virion release & spread

• Human genera: Influenza A, B (seasonal), C (mild)

  • Influenza A sub-typed by 18 HA (H1–H18) & 11 NA (N1–N11) variants; swine are “mixing vessels” for reassortment

• Antigenic drift: point mutations in HA/NA → annual epidemics

• Antigenic shift: reassortment of segments → new HA/NA combo → pandemics

COVID-19 (SARS-CoV-2)

• Family: Coronaviridae, Betacoronavirus lineage

• Structure

  • Positive-sense RNA genome bound to nucleoprotein (N)

  • Envelope with Spike (S) glycoprotein, Membrane (M) protein, Envelope (E) protein

• Entry

  • S1 subunit binds ACE2 receptor; TMPRSS2 primes S2 fusion → endocytosis/ membrane fusion; ACE2 down-regulated

• Replication: translation of RNA-dependent RNA polymerase → nested mRNA synthesis → assembly in ER-Golgi → exocytosis

• Pathogenesis links to RAAS imbalance: decreased ACE2 → excess angiotensin II → vasoconstriction, inflammation, fibrosis

• High mutation rate ⇒ antigenic drift → "variants of concern"

Histoplasmosis

• Fungus: Histoplasma capsulatum (dimorphic)

  • Mold in environment; yeast intracellular in macrophages

• Acquisition: inhalation of microconidia from soils enriched with bat/bird guano (caves, chicken coops)

• Disease

  • Pulmonary lesions mimic TB; 0.1\% disseminate (immunosuppressed)

• Treatment: itraconazole; amphotericin B for severe disease

Pneumocystis Pneumonia (PCP)

• Etiology: Pneumocystis jirovecii (yeast-like fungus)

• Hallmark opportunistic infection in AIDS (CD4 < 200 cells\/µL)

• Life cycle

  • Thick-walled cyst in alveoli → ruptures → 8 trophozoites → attach to type I pneumocytes → foamy exudate blocks O₂ exchange

• Therapy: trimethoprim-sulfamethoxazole (TMP-SMX); prophylaxis in high-risk patients