Streptococcus pneumoniae infection pathophysiology

Streptococcus pneumoniae infection Microchapters
Home
Patient Information
Overview
Classification Community Acquired Pneumonia Endocarditis Sinusitis Bronchitis Meningitis
Cause
Laboratory Findings
Medical Therapy
Primary Prevention

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Pathogenesis

S. pneumoniae is normally found in the nasopharynx of 5-10% of healthy adults, and 20-40% of healthy children. It can be found in higher amounts in certain environments, especially those where people are spending a great deal of time in close proximity to each other (day cares, army barracks). It attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. This normal colonization can become infectious if the organisms are carried into areas such as the Eustachian tube or nasal sinuses where it can cause otitis media and sinusitis, respectively. Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, or smoking-induced ciliary paralysis might be contributing factors). Once the organism makes its way to a site where it is not normally found, it activates the complement protein group, stimulates cytokine production, and attracts white blood cells (specifically neutrophils). The organism's polysaccharide capsule makes it resistant to phagocytosis, and if there is no pre-existing anticapsular antibody, alveolar macrophages cannot adequately kill the pneumococci. The organism spreads to the blood stream (where it can cause bacteremia) and is carried to the meninges, joint spaces, bones, and peritoneal cavity, and may result in meningitis, brain abscess, septic arthritis, or osteomyelitis.

S. pneumoniae has several virulence factors, including the polysaccharide capsule mentioned earlier, that help it evade a host's immune system. It has pneumococcal surface proteins that inhibit complement-mediated opsonization, and it secretes IgA1 protease that will destroy secretory IgA produced by the body.

Virulence Factors

S. pneumoniae expresses different virulence factors on its cell surface and inside the organism. These virulence factors contribute to some of the clinical manifestations during infection with S. pneumoniae.

• Polysaccharide capsule -prevents phagocytosis by host immune cells by inhibiting C3b opsonization of the bacterial cells
• Pneumolysin (Ply) -a 53-kDa protein that can cause lysis of host cells and activate complement
• Autolysin (LytA) -activation of this protein lyses the bacteria releasing its internal contents (i.e. pneumolysin)
• Hydrogen peroxide - causes damage to host cells (can cause apoptosis in neuronal cells during meningitis) and has bactericidal effects against competing bacteria (Staphylococcus aureus)
• Pili - hair-like structures that extend from the surface of many strains of S. pneumoniae. They contribute to colonization of upper respiratory tract and increase the formation of large amounts of TNF by the immune system during sepsis, raising the possibility of septic shock
• Choline binding protein A (CbpA) -an adhesin that can interact with carbohydrates on the cell surface of pulmonary epithelial cells
• Protective Antigen (PspA) -can inhibit complement-mediated opsonization of pneumococci

Humoral immunity

In the 19th century, it was demonstrated that immunization of rabbits with killed pneumococci protected them against subsequent challenge with viable pneumococci. Serum from immunized rabbits or from humans who had recovered from pneumococcal pneumonia also conferred protection. In the 20th century, the efficacy of immunization was demonstrated in South African miners.

It was discovered that the pneumococcus's capsule made it resistant to phagocytosis, and in the 1920s it was shown that an antibody specific for capsular polysaccharide aided the killing of S. pneumoniae. In 1936, a pneumococcal capsular polysaccharide vaccine was used to abort an epidemic of pneumococcal pneumonia. In the 1940s, experiments on capsular transformation by pneumococci first identified DNA as the material that carries genetic information.

In 1900, it was recognized that different serovars of pneumococci exist, and that immunization with a given serovar did not protect against infection with other serovars. Since then over ninety serovars have been discovered, each with a unique polysaccharide capsule which can be identified by the quellung reaction. Because some of these serovars cause disease more commonly than others, it is possible to provide reasonable protection by immunizing with less than 90 serovars; the current vaccine contains 23 serovars (i.e., it is "23-valent").

The serovars are numbered according to two systems: the American system, which numbers them in the order in which they were discovered, and the Danish system which groups them according to antigenic similarities.

Interaction with Haemophilus influenzae

Both H. influenzae and S. pneumoniae can be found in the human upper respiratory system. A study of competition in a laboratory revealed that, in a petrì dish, S. pneumoniae always overpowered H. influenzae by attacking it with a hydrogen peroxide and stripping off surface molecules that H. influenzae needs for survival.

When both bacteria are placed together into a nasal cavity, within 2 weeks, only H. influenzae survives. When both are placed separately into a nasal cavity, each one survives. Upon examining the upper respiratory tissue from mice exposed to both bacteria, an extraordinarily large number of neutrophils immune cells were found. In mice exposed to only one bacteria, the cells were not present

Lab tests show that neutrophils that were exposed to already dead H. influenzae were more aggressive in attacking S. pneumoniae than unexposed neutrophils. Exposure to killed H. influenzae had no effect on live H. influenzae.

Two scenarios may be responsible for this response:

1. When H. influenzae is attacked by S. pneumoniae, it signals the immune system to attack the S. pneumoniae
2. The combination of the two species together sets off an immune system alarm that is not set off by either species individually.

It is unclear why H. influenzae is not affected by the immune system response.