Chapter Summary

23.1

  • The normal microbiota present on body surfaces constantly changes.
  • Normal microbiota can cause disease if microbes breach the surfaces they colonize and gain access to the circulation or deeper tissues.
  • Normal microbiota help prevent disease by inhibiting colonization by pathogens.
  • Colonization of skin by microbes is difficult owing to surface dryness, an acidic pH, high salinity, and the presence of degradative enzymes.
  • Skin microbiota consists primarily of Gram-positive microbes, including Propionibacterium acnes, which can cause acne.
  • Microbe-free areas of the body are the lungs, cerebrospinal fluid, and bladder. The eyes are generally microbe-free, although some microbes can be present for short periods.
  • Oral and nasal surfaces are colonized by aerobic and anaerobic microbes.
  • The intestine is populated by 109–1011 microbes per gram of feces in a ratio of approximately 1,000 anaerobes to one aerobe.

23.2

  • Opportunistic pathogens infect only compromised hosts.
  • Benefits of commensal microbes include interfering with pathogen colonization, production of immunomodulatory proteins, and potential use as vaccine delivery vehicles.
  • Gnotobiotic animals are germ-free or colonized by a known set of microbes.

23.3

  • The immune system consists of both innate and adaptive mechanisms that recognize and eliminate pathogens.
  • Innate immunity includes physical barriers and some cellular responses to various microbial structures.
  • Adaptive immunity is a cellular response to specific structures (antigens) in which a memory of exposure is produced.
  • Myeloid bone marrow stem cells differentiate to form cells of the innate im mune system—phagocytic PMNs, monocytes, macrophages, antigen- presenting dendritic cells, and mast cells.
  • Lymphoid stem cells differentiate into natural killer cells (part of the innate immune system) and lymphocytes (cells of the adaptive immune system). Lymphocytes are classified as B cells, which ultimately produce antibodies; and T cells, which regulate adaptive immunity.

23.4

  • Skin defenses against invading microbes include closely packed keratinocytes and a SALT lymphoid system made up largely of phagocytic Langerhans cells.
  • Mucous-membrane defenses involve secreted enzymes, cytokines, and GALT tissues, such as Peyer’s patches, that contain phagocytic M cells.
  • M cells in gut-associated lymphoid tissues sample bacterial cells at their surface and release pieces of them to immune system cells.
  • Phagocytic alveolar macrophages inhabit lung tissues, contributing to nonspecific defense.
  • Chemical barriers against disease include cationic defensins, acid pH in the stomach, and superoxide produced by certain cells.
  • Pathogen-associated molecular patterns (PAMPs) are recognized by Toll-like receptors (TLRs) found on many host cells. Binding triggers release of chemical signal molecules that activate innate and adaptive immune mechanisms.

23.5

  • Inflammation begins with a mechanism (extravasation) that moves neutrophils from the bloodstream into infected tissues.
  • Macrophages in tissues engulf microorganisms and release vasoactive factors that increase vascular permeability, cytokines that stimulate production of selectin receptors, and chemoattractant molecules that call in neutrophils.
  • Extravasation is the process by which neutrophils pass between cells of the endothelial wall. Once out of the circulation, the neutrophils travel to the site of infection.
  • Bradykinin causes the release of prostaglandins, which produce pain in the affected area.
  • Chronic inflammation results from the persistent presence of a foreign object.

23.6

  • Phagocytosis is selective for particles recognized as foreign to the body.
  • Oxygen-independent and oxygen-dependent mechanisms of killing are initiated by fusion between a lysosome and a bacteria-containing phagosome.
  • The oxidative burst, a large increase in oxygen consumption during phagocytosis, results in the production of superoxide ions, nitric oxide, and other reactive oxygen species.
  • Autophagy is a process by which intracellular bacteria can be sequestered from the cytoplasm (via an autophagosome) and killed following fusion with a lysosome.

23.7

  • Interferons are species-specific molecules that can nonspecifically interfere with viral replication (type I) and modulate the immune system (type II).
  • Natural killer (NK) cells are a class of white blood cell that destroy cancer cells or cells harboring microorganisms.
  • Natural killer cells target host cells that have lost MHC class I receptors as a result of infection or cancer, or host cells that are coated with antibody ( antibody-dependent cell-mediated cytotoxicity, ADCC).
  • Natural killer cells kill by inserting perforin pores into the membranes of target cells.
  • Toll-like receptors (TLRs) on host cells recognize different pathogen-associated molecular patterns (PAMPs).

23.8

  • Complement is a series of 20 proteins naturally present in serum.
  • Activation of the complement cascade results in a pore being introduced into target membranes.
  • The three pathways for activation are the classical, alternative, and lectin pathways.
  • The alternative activation pathway begins when complement factor C3b is stabilized by interaction with the LPS of an invading microbe.
  • The cascade of protein factors C3b r B r factor D r properdin r C5 r C6 r C7 r C8 and C9 results in formation of a membrane attack complex in target membranes.
  • C-reactive protein in serum is activated when bound to microbial structures and will convert C3 to C3b, which can start the complement cascade.

23.9

  • The hypothalamus acts as the body’s thermostat.
  • Exogenous and endogenous pyrogens elevate body temperature by stimulating prostaglandin production.
  • Prostaglandins change the responsiveness of thermosensitive neurons in the hypothalamus.