Injury may be due to local or systemic release of bacterialproducts, including endotoxins (LPS), exotoxins, or superantigens, combined with the immune response.
Absence of an immune response may reduce the damageinduced by some infections; conversely, immunocompromisecan allow uncontrolled expansion of opportunistic infectionsthat can directly cause injury.
Chronic immunological and inflammatory diseases and cancerhave been associated with specific microorgansims.
Humoral and cellular immune responses that protect  the host from most infections are discussed in Chapter 5. Not surprisingly, microorganisms have developed many means to resist and evade the immune system (
Fig. 9.9 ). These mechanisms of escaping the immune response  are important determinants of microbial virulence and pathogenicity.
Antigenic variation. Neutralizing antibodies against microbial antigens block the ability of microbes to infect cells and recruit immune cells to kill pathogens. To escape recognition, microbes use many strategies that involve genetic mechanisms for generating antigenic variation. The low fidelity of viral RNA polymerases (HIV and influenza virus) and reassortment of viral genomes (influenza viruses) create viral antigenic variation (
Table 9.7 ). Borrelia species switch their surface antigens via gene rearrangement. Trypanosoma species have many genes for their major surface antigen, VSG, and vary the expression of this surface protein. There are more than 90 different serotypes of S. pneumoniae, each with a different capsular polysaccharide.
Modification of surface proteins. Host cationic antimicrobial peptides, including defensins, cathelicidins,
Modulation of surface structure Inhibition of phagocytosis to avoid recognition (e.g., antigenic variability)
Inhibition of phagosome
Modulate: Signal transduction Gene expression Cell death and thrombocidins, provide important initial defenses against invading microbes. These peptides bind the bacterial membrane and form pores, killing the bacterium by osmotic lysis. Bacterial pathogens (Shigella spp., S. aureus) avoid killing by making surface molecules that resist binding of anti-microbial peptides, or that inactivate or downregulate anti-microbial peptides.
• Overcoming antibodies and complement. Host defense includes coating of bacteria with antibodies or the complement protein C3b (opsonization) to facilitate phagocytosis by macrophages. However, the facultative intracellular pathogen M. tuberculosis subverts the complement response by activating the alternative
Table 9.7 Mechanisms of Anti-genic Variation
Genetic rearrangement Borrelia burgdorferi Lyme disease(e.g., gene recombination, Neisseria gonorrhoeae Gonorrheagene conversion, Trypanosoma spp. African sleeping site-specific inversion)sickness
Plasmodium spp. Malaria