compartments. Many bacterial pathogens live and replicate in extracellular spaces, either within tissues or on the surface of the epithelia that line body cavities. Extracellular bacteria are usually susceptible to killing by phagocytes, an important arm of the innate immune system, but some pathogens, such as Staphylococcus and Streptococcus species, are protected by a polysaccharide capsule that resists engulfment. This can be overcome to some extent by the help of another component of innate immunity—complement—which renders the bacteria more susceptible to phagocytosis. In the adaptive immune response, bacteria are rendered more susceptible to phagocytosis by a combination of antibodies and complement.
Infectious diseases differ in their symptoms and outcome depending on where the causal pathogen replicates within the body—the intracellular or the extracellular compartment—and what damage it does to the tissues (Fig. 2.4). Pathogens that live intracellularly frequently cause disease by damaging or killing the cells they infect. Obligate intracellular pathogens, such as viruses, must invade host cells to replicate. Facultative intracellular pathogens, such as mycobacteria, can replicate either intracellularly or outside the cell. Two strategies of innate immunity defend against intracellular pathogens. One is to destroy pathogens before they infect cells. To this end, innate immunity includes soluble defenses such as antimicrobial peptides, as well as phagocytic cells that can engulf and destroy pathogens before they become intracellular. Alternatively, the innate immune system can recognize and kill cells infected by some pathogens. This is the role of the natural killer cells (NK cells), which are instrumental in keeping certain viral infections in check before cytotoxic T cells of the adaptive immune system become functional. Intracellular pathogens can be subdivided further into those that replicate freely in the cell, such as viruses and certain bacteria (for example, Chlamydia, Rickettsia, and Listeria), and those that replicate inside intracellular vesicles, such as mycobacteria. Pathogens that live inside macrophage vesicles may become more susceptible to being killed after activation of the macrophage as a result of NK-cell or T-cell actions (see Fig. 2.3).
Many of the most dangerous extracellular bacterial pathogens cause disease by releasing protein toxins; these secreted toxins are called exotoxins (see Fig. 2.4). The innate immune system has little defense against such toxins,
Anatomic barriers and initial chemical defenses.
Direct mechanisms of tissue damage by pathogens Direct cytopathic effect Variola Varicella-zoster Hepatitis B virus Polio virus Measles virus Infuenza virus Herpes simplex virus Human herpes virus 8 (HHV8) Smallpox Chickenpox, shingles Hepatitis Poliomyelitis Measles, subacute sclerosing panencephalitis Infuenza Cold Kaposi's sarcoma sores Exotoxin production Streptococcus pyogenes Staphylococcus aureus Corynebacterium diphtheriae Clostridium tetani Vibrio cholerae Tonsillitis, scarlet fever Boils, toxic shock syndrome, food poisoning Diphtheria Tetanus Cholera Endotoxin Escherichia coli Haemophilus infuenzae Salmonella typhi Shigella Pseudomonas aeruginosa Yersinia pestis Gram-negative sepsis Meningitis, pneumonia Typhoid fever Bacillarydysentery Wound infection Plague