strategies to avoid detection by pattern recognition receptors and destruction by antibody, complement, and antimicrobial peptides.
Extracellular bacterial pathogens replicate outside of host cells, whether on the surfaces of barrier tissues they colonize (for example, gastrointestinal or respiratory tract), or in tissue spaces or blood following invasion across barrier epithelia. Both Gramnegative and positive species are pathogenic, and, as discussed in Section 1110, they typically elicit type 3 immunity, which orchestrates neutrophilic responses, the development of opsonizing and complementfixing antibodies, and the production of antimicrobial peptides by barrier epithelial cells and immune cells that clear these microbes from barrier epithelia and prevent their invasion. Some of the MAMPS expressed by Gramnegative and positive bacteria are distinct, but share similar immunecell activating properties. Gramnegative pathogens contain LPS, a potent activator of TLR4, in their outer cell membrane, whereas the cell wall of Grampositive pathogens contains peptidoglycans, which activate TLR2 and NOD1 and NOD2. One strategy of immune evasion used by these pathogens is therefore shielding of surface MAMPs to avoid their detection by pattern recognition receptors on immune cells (Fig. 13.17). Several Gramnegative pathogens modify the lipid A core of LPS with carbohydrates and other moieties that interfere with TLR4 binding. Indeed, some bacteria produce variants of lipid A that act as TLR4 antagonists rather than agonists. Select Grampositive pathogens have evolved mechanisms to modulate peptidoglycan recognition by NODs, or to produce hydrolases that degrade peptidoglycan.
Fig. 13.17 Mechanisms used by bacteria to subvert the host immune system. listed are examples of immune evasion/subversion mechanisms used by different strains of extracellular and intracellular bacterial pathogens. examples of the strains of bacteria that employ each mechanism are listed in the far right column (e.g., Streptococcus pneumoniae, Porphyromonus gingivalis, Pseudomonas aeruginosa, Brucella abortus, Yersinia pestis).
Fig. 13.18 Host defense against Streptococcus pneumoniae is type specific. the different strains of S. pneumoniae have antigenically distinct capsular polysaccharides. the capsule prevents effective phagocytosis until the bacterium is opsonized by specific antibody and complement, allowing phagocytes to destroy it. antibody against one type of
S. pneumoniae does not cross-react with the other types, so an individual immune to one type has no protective immunity to a subsequent infection with a different type. an individual must generate a new adaptive immune response each time he or she is infected with a different type of S. pneumoniae.