A limited number of Grampositive pathogens can also shield their outer cell membrane with a thick carbohydrate capsule. In addition to inhibiting recognition of peptidoglycan and activation of the alternative pathway of complement, the capsule prevents antibody and complement deposition on the bacterial surface, thereby avoiding direct damage by the membraneattack complex of the complement cascade. The capsule also impairs clearance of the pathogen by phagocytes (see Fig. 13.17). In the case of Streptococcus pneumoniae, an important cause of bacterial pneumonia, the carbohydrate capsule also serves as a platform for antigenic variation to modulate the expression of surface antigenic epitopes recognized by antibody. Over 90 known types of S. pneumoniae are distinguished by differences in the structure of their polysaccharide capsules. The different types are distinguished by using specific antibodies as reagents in serological tests and so are often known as serotypes. Infection with one serotype can lead to typespecific immunity, which protects against reinfection with that type but not with a different serotype. Thus, from the point of view of the adaptive immune system, each serotype of S. pneumoniae represents a distinct organism, with the result that essentially the same pathogen can cause disease many times in the same individual (Fig. 13.18). Similarly, antigenic variation mediated by DNA rearrangement also occurs in bacteria and helps to account for the success of enteropathogenic E. coli, or of Neisseria species, which cause gonorrhea and meningitis. Fimbriae or pili are expressed on the bacterial surface and used for attachment to hostcell surfaces and are major antigenic targets for antibodymediated blockade of bacterial attachment and colonization. The gene locus encoding the expressed Neisseria pilus (pilE) can undergo recombination with partial pilin genes stored in ‘silent’ (pilS) loci to generate a constantly shifting pilus for display on the bacterial surface. By constantly changing the expressed pilus, the bacterium evades antibodymediated immune clearance.
Among other antiimmune strategies used by extracellular pathogens are mechanisms to inactivate the C3 convertase of the complement cascade; the expression of Fcbinding proteins that block functional antibody binding to the bacterium (for example, Protein A); and the decoration of the bacterial surface with host inhibitors of complement (for example, factor H). These bacteria have also evolved mechanisms to defeat antimicrobial peptides (AMPs; for example, defensins and cathelicidins). These small cationic and amphipathic peptides have significant antimicrobial activity by inserting into negatively charged cell membranes to generate pores that lyse the bacterium. Pathogens can alter their membrane composition to minimize AMP binding, and can produce proteases that degrade the AMPs.