Mechanisms of Disease: Pathogenesis of Pneumococcal Infection

Capsular polysaccharide also stimulates the production of serotype-specific, protective antibody.5 ,15 There are 84 known capsular types, and the current 23-valent polysaccharide vaccine was formulated to include the serotypes that cause 85 to 90 percent of the bacteremic infections in the United States.16 Cell Wall Although covered by capsular polysaccharide, the cell wall is accessible to some components of the acute-phase response, as evidenced by its ability to fix complement.17 The cell wall is a dynamic structure composed of more than a dozen glycopeptides that are continuously inserted into and released from this circumferential, extracellular macromolecule.9 ,18 Specific components of the cell wall change with the acquisition of penicillin resistance.19 The components of pneumococcal cell walls stimulate the recruitment of leukocytes into the lung and subarachnoid space,10 ,14 enhance the permeability of cerebral endothelia14 and pulmonary alveolar epithelia,10 induce the production of cytokines,20 -23 initiate the procoagulant cascade,24 stimulate the production of platelet-activating factor (PAF),25 cause direct damage to neurons,26 and alter cerebral blood flow and vascular-perfusion pressure.27 ,28 Cell-wall components released by enzymatic degradation are more potent chemotactic factors than are intact cell walls -- a finding relevant to the consequences of bacterial lysis induced by antibiotics.29 The presence of teichoic acid in a cell-wall component enhances its inflammatory activity.20 ,24 ,29 An unusual and important feature of pneumococcal teichoic acid is the presence of phosphorylcholine.30 Phosphorylcholine is also a critical determinant of the bioactivity of PAF.