Pneumonia

Pneumonia + influenza =

7^th leading cause of death in US

Pneumonia Deaths

About 63,000 deaths per year

Pneumonia causes

Can be caused by viruses, fungi, bacteria, or irritants

Pneumonia variants

• Streptococcus pneumoniae– about 25% of causes, 40,000 deaths

• Mycoplasma pneumoniae– about 20% of cases

• Chlamydia pneumoniae– about 5-10% of cases

• Legionella pneumoniae– rare but has high mortality

Symptoms

• Cough

• Fever

• Shaking, "teeth-chattering" chills 

• Fast, often shallow, breathing and the feeling of being short of breath

• Chest wall pain that is often made worse by coughing or breathing in

• Fast heartbeat.

• Feeling very tired (fatigue) or feeling very weak (malaise). 

• Nausea and vomiting 

• Diarrhea

Diseases of S. pneumoniae

• Gram+, diplococci, capsule

• Pneumonia

• Otitis media (earache)

• Meningitis

Routes of S. pneumoniae

• Normal biota of nasopharynx

• Move via Eustachian tube to middle ear

• From nasopharynx to lower respiratory tract

• From inflamed lungs to blood

Aspiration of S. pneumoniae

1. Adherence to alveolar macrophages:exposure of cell wall components

2. Inflammation response

3. Red hepatization and consolidation of lung parenchyma

4. Leukocyte infiltration

5. Gray hepatization and deposition of fibrin on pleural surfaces; phagocytosis in alveoli

6. Resolution of infection: macrophages in alveoli ingest and remove degenerated neutrophils, fibrin and bacteria

S. pneumoniae Capsule

• Polysaccharide

• Inhibits phagocytosis by inhibiting opsonization by C3b

• 80 different serotypes; 23 serotypes of pathogenic S. pneumoniae

What does the Capsule do?

• Decreases phagocytosis

• Prevents C3b binding

• Binds protein H

• Allows colonization in mucosal layer

Adhesins of S. pneumoniae

• Psp C– important for colonization of the trachea and upper respiratory system

  • Binds PigR

• Pav A– fibronectin binding

Reverse Transcytosis

• Binds IgA transporter, PigR

• Induces reverse transcytosis across respiratory tract epithelium

Phase Variation

• Epigenetic change in gene expression from transparent to opaque

• Transparent

  • More teichoic acid

• Opaque

  • Larger capsule

  • Better ability to evade immune system

Evasion of the Immune System

• IgA protease on capsule cleaves antibodies

• PspA prevents C3b binding

• EndA degrades neutrophil nets

Autolysis

• Autolysin LytA produced in stationary stage

• Lysis of bacterial cells 

• Release of pneumolysin and cell wall components

• Triggers inflammation

• Reduces phagocytosis

• Stops cilia

• Inhibits complement

Cell wall components

• Phosphorylcholine– binds C reactive protein, activates complement

• Peptidoglycan/teichoic acid– highly inflammatory; activates alternative complement pathway

Pneumolysin

• Binds cholesterol; makes holes in cholesterol containing cells

• Damages endothelial cells– blood enters lung

• Damages alveolar cells

• Activates complement– produces an inflammatory response

S. pneumoniae Meningitis

• Middle ear to mastoid sinus

• Choroid plexus arteries

• Through BBB

S. pneumoniae Sepsis

• Inflammation activates PAF

• ChoP binds PAF 

• Transcytosis through endothelial cells

Vaccines

• Conjugate (Prevnar)– made from capsular carbohydrates from 7 most common strains covalently linked to diphtheria toxin

• Pneumococcal polysaccharide vaccine (PPV or pneumovac)– made from capsular carbohydrates from 23 strains of S. pneumoniae