HumanMicrobe Interactions

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Chapter 21

• Human-Microbe Interactions

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Human-Microbe Interactions

• Normal flora the hundreds of species/billions
  of individual microbes that live on or in the
  human body.
• Pathogens microbial parasites (organisms that
  live on or in a host organism, causing damage to
  the host).
• Virulence the quantitative measure of
  pathogenicity.
• Virulence vs. resistance of the host are
  constantly changing.
• Infection microorganism is established and
  growing in a host (note that the host may or may
  not be harmed).
• Disease damage or injury to the host that
  impairs host function. Infection ? disease.

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Human-Microbe Interactions (cont.)

• Why would microorganisms want to live within an
  animals body?
• Is the animal body a uniform microbial
  environment?
• What areas of the body are normally colonized by
  microorganisms?
• Infections often begin at sites in the animals
  mucous membranes. Where are mucous membranes
  located in the body?
• What is mucus made of and what is its purpose?
• Why do mucosal surfaces have a larger variety of
  organisms associated than nonmuscosal surfaces?

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Normal Flora of the Skin

• Avg. adult has 2 m2 of skin surface.
• Skin is not favorable to microbial growth since
  it is subject to drying. Most microbes are
  associated with the sweat glands.
• The flora of the skin consists of resident and
  transient populations of microbes. Resident
  microbes live and multiple on the skin, whereas
  transient flora almost always are unable to
  multiple and usually die.
• Resident flora remains fairly constant, although
  it can be affected by several factors. What are
  3 of these factors?

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Normal Flora of the Oral Cavity

• Saliva contains antibacterial enzymes lysozyme
  and lactoperoxidase (also present in milk).
• Saliva (pervasive, although not the best nutrient
  source), food particles, and epithelial debris
  provide nutrients for microbes.
• Microbes colonize many surfaces in the mouth,
  including teeth and gingival crevices. The flora
  of the mouth changes with stages of growth, ex.
  acquisition of teeth.
• A thin organic film forms on the tooth surface,
  to which acidic glycoproteins from the saliva
  attach, enabling only a few species of
  Streptococcus (ex. S. mutans) to adhere.
• Dental caries tooth decay infectious disease
  caused by microbes. High sugar diets promote
  tooth decay because lactic acid bacteria ferment
  the sugars to lactic acid ? decalcification of
  the enamel ? proteolysis of the matrix of tooth
  enamel ? further infection/decay. Fluoride
  prevents the decalcification step.
• Microorganisms in the mouth can also cause other
  infections.

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Normal Flora of the Gastrointestinal Tract

• The stomach is not hospitable to microbes due to
  its low pH (pH 2), except Helicobacter pylori,
  which causes ulcers.

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Normal Flora of the Respiratory Tract

• Upper respiratory tract nasopharynx, oral
  cavity, and throat.
• Staphylococci, streptococci, diphtheroid
  bacillia, and gram-neg. cocci, as well as
  potentially harmful bacteria (ex. Staph. aureus
  and Strep. Pneumoniae) are often part of the
  normal flora of the nasopharynx of healthy
  individuals.
• Lower respiratory tract trachea, bronchi, and
  lungs. The lower respiratory tract is
  essentially sterile. Ciliated epithelium beat
  contaminants upward.

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Normal Flora of the Urogenital Tract

• The bladder itself is usually sterile, but the
  epithelial cells lining the urethra are colonized
  by facultatively aerobic gram-neg. rods and
  cocci, including E. coli, Proteus mirabilis, etc.
• Occasionally, these organisms become
  opportunistic pathogens. Factors such as local
  pH changes allow organisms to multiply and become
  pathogenic.
• The vagina of the adult female is generally
  weakly acidic and contains significant amounts of
  the polysaccharide glycogen. Lactobacillus
  acidophilus, yeasts such as Candida,
  streptococci, and E. coli may also be present.
  Before puberty, the vagina is alkaline and does
  not produce glycogen. L. acidophilus is absent
  at this time. After menopause, the flora
  resembles that before puberty.

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Entry of the Pathogen into the Host

• Virulence the relative ability of a pathogen to
  cause disease.
• Organisms must penetrate the skin, mucous
  membranes, or intestinal epithelium, which
  normally act as barriers.
• Most microbial infections begin at breaks or
  wounds in the skin, etc.
• Bacteria or viruses adhere specifically to
  epithelial cells through protein-protein
  interactions on the surfaces of the host and
  pathogen cells. These interactions are often
  cell and species specific.
• Bacterial adherence not dependent on this type of
  attachment include structures such as a capsule,
  glycocalyx, and slime layer.
• Fimbriae and pili are also used for attachment of
  the pathogen to the host.
• Most pathogens penetrate the epithelium to
  initiate pathogenicity invasion, although some
  produce toxins that may eliminate normal flora or
  cause breaks in the epithelium, allowing access
  of the pathogen to the underlying tissues.

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Colonization and Growth

• Colonization multiplication of a pathogen after
  it has gained access to the hosts tissues.
• The initial inoculum of a pathogen is rarely
  sufficient to cause damage, so it must find
  appropriate nutrients and environmental cond. in
  order to grow which is most imporant?
  Vitamins, growth factors, trace elements may be
  in short supply.
• Pathogens usually remain localized at the site of
  entry, but can pass through the lymphatic
  vessels, and eventually to the blood, where it
  can travel around the body ? bacteremia.

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Virulence

• Measuring virulence calculated as LD50 (lethal
  dose50) dose of an agent that kills 50 of the
  animals in a test group.
• Highly virulent pathogens show little difference
  between cells required for LD50 and required
  for LD100. This can be as little as a few cells.
• When pathogens are kept in lab culture and not
  passed through animals, their virulence is often
  decreased or lost attenuated. Why does this
  occur?
• Toxicity the ability of an organism to cause
  disease by means of a preformed toxin that
  inhibits host cell function or kills host cells,
  ex. Clostridium tetani ? tetanus exotoxin.
• Invasiveness ability of an organism to grow in
  host tissue in such large s that the pathogen
  inhibits host function. Virulence factor
  allowing invasiveness may not be a toxin, but may
  be something such as a capsule, ex. Streptococcus
  pneumoniae.

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Virulence Factors

• Virulence factors pathogen-produced
  extracellular proteins that aid in the
  establishment and maintenance of disease.
• Most are enzymes that help the pathogens colonize
  and grow, ex. enzymes that help the pathogen to
  spread within the tissues.
• Fibrin clots form at the site of microbial
  invasion to limit infection, but some organisms
  can dissolve these clots. Other organisms
  promote the formation of clots in order to
  protect themselves from what?

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Virulence Factors
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Exotoxins

• Exotoxins proteins released extracellularly as
  the organism grows.
• 3 classes
• 1. Cytolytic toxins attacking cell
  constituents causing lysis, ex. hemolysins.
• 2. A-B toxins consists of 2 subunits - one
  binds to cell surface receptor and the other is
  transferred into the cell to damage the cell, ex.
  diphtheria toxin, botulism toxin, and tetanus
  toxin.
• 3. SuperAg toxins stimulate large s of
  immune response cells.

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Enterotoxins

• Enterotoxins exotoxins that act on the small
  intestine, generally causing massive secretion of
  fluid into the intestinal lumen, leading to
  vomiting and diarrhea.
• Ex. cholera toxin, E. coli O157H7 toxin.

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Endotoxins

• Endotoxins generally cell-bound toxins that are
  released in large amounts only when cells are
  lysed.
• e.x. LPS of gram-neg. bacteria.
• Fever is an almost universal symptom because host
  cells are stimulated to release endogenous
  pyrogens, affecting the temp.-controlling center
  of the brain.

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Nonspecific Innate Resistance to Infection

• Natural host resistance varies.
• Age Newborns havent acquire adequate normal
  flora, the elderly suffer from declining ability
  to make an effective immune response to
  respiratory pathogens, for ex.
• Stress such as fatigue, exertion, poor diet,
  dehydration, drastic climatic changes, increase
  the incidence and severity of infectious
  diseases. Hormones produced under stress
  influence the immune system, for ex. by
  suppressing it.
• Diet can alter the composition of the normal
  flora, ex. either lack of a nutrient can put the
  host at a disadvantage or deprive a pathogen of
  an essential nutrient.

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Nonspecific Innate Resistance to Infection
(cont.)

• Physical and Chemical Defenses include
  structural integrity of tissue surfaces (skin,
  mucosum), cilia, secretions (ex. fatty acids and
  lactic acid produced by sebaceous glands),
  stomach acid, lysozyme.
• Most pathogens must first adhere and colonize at
  the site of exposure and this interaction is very
  specific for the type of cells/tissue. Pathogens
  might not survive interactions in other locations
  in the body besides the target tissue.
• Compromised host host in which one or more
  resistance mechanisms are inactive and in which
  the probability of infection is increased, ex.
  hospital patients (cancer, heart disease,
  transplants, AIDS, surgery, routine lab tests),
  people outside the hospital (smokers, drinkers,
  IV drug users, sleep-deprived, malnourished), or
  people with certain genetic diseases.

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Inflammation

• Inflammation nonspecific reaction to noxious
  stimuli such as toxins and pathogens.
• Inflammatory response redness, swelling, pain,
  and heat.
• Cytokines produced by leukocytes mediate
  inflammation.
• Septic shock systemic inflammation results in
  severe swelling (edema) and uncontrollable fever.
  Inflammation spreads throughout the body via the
  circulatory or lymphatic systems.

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Fever

• Normal body temp. 37C.
• Fever abnormal increase in body temp., usually
  caused by infection.
• Pyrogenic fever-inducing. Fevers 40C (104F)
  benefit the pathogen because host tissues are
  further damaged.
• Types of fever
• 1. Continuous body temp. is remains elevated
  over at 24-hr. period, but does not vary by more
  than 1C.
• 2. Remittant temp. is abnormal over a 24-hr.
  period, but varies by more than 1C.
• 3. Intermittant temp. is normal for part of the
  day and elevated for part of the day. Most
  infectious diseases elicit some intermittant
  fever.