Bacterial Pathogenesis

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Bacterial Pathogenesis

• Reading requirement Brocks Chapter 28

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Bacterial Pathogenesis (I) Host Defenses

• Bacterial disease is the result of a complex set
  of interactions between bacteria and the host
  they are attempting to colonize
• In the process of evolution, humans have
  developed a variety of ways of protecting
  themselves from potential parasites such as
  bacteria host defenses
• At the same time, bacteria have been evolving
  ways to circumvent the host defenses bacterial
  virulence factors

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Traditional studies of bacterial diseases

• Focus on how to diagnose the disease and what
  treatment should be given Bugs and Drugs
• Antibiotic treatment may eliminate all of the
  bacteria from the infected area, but may not
  restore the patient to full health if
  irreversible tissue damage has been done
• In many types of bacterial infections, the
  majority of damage associated with the disease is
  caused by host defense systems trying to clear
  the bacteria rather than by direct action of
  bacteria themselves

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Bacterial Pathogenesis

• Focus on understanding how the human body defends
  itself against bacterial pathogens and how some
  bacteria manage to evade these defenses

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Host Defenses Against Bacterial Pathogens

• Within any human population, there is
  considerable variation in the ability to resist
  bacterial infections. When exposed to a bacterial
  pathogen, some will be completely unaffected,
  whereas other will become sick and die
• Understanding what defenses are most important in
  preventing various types of bacterial defenses is
  critical for control of bacterial infections
  especially since bacterial resistance to
  antibiotics is increasing vaccine development

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Host Defenses

• Preventing contact between host and pathogen
  defenses of body surfaces
• Preventing the development of disease defenses
  of tissue and blood

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Defenses of Body Surfaces

• Skin and mucosal surfaces the bodys first line
  of defense
• Colonization of bacteria on skin surface or
  mucosal membranes is the first step in most types
  of bacterial disease

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Defenses of Body Surfaces

• Two categories
• Nonspecific means that a particular defense is
  effective against most bacteria
• Specific refers to a defense that is directed
  toward a particular strain or species of bacteria
• Constitutive means that the defense is always
  present
• Induced refers to a defense that appears only
  after the bacterium has been encountered, e.g,
  antibodies

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Skin
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Mucous Membranes surfaces that line the
gastrointestinal tract, respiratory tract, and
urogenital tract
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Special defenses of specific mucosal surfaces

• Mouth and respiratory tract
• In mouth and throat, the flow of saliva which
  contains lysozyme, lactoferrin and sIgA limits
  the accumulation of bacteria
• The mouth and upper part of the airway are
  protected by resident microflora (mostly are
  gram-positive bacteria)
• The lungs are normally free of bacteria the path
  from the nose to the lungs is curved, breathing
  and cough removed large particles that contain
  bacteria alveolar macrophages ingest and kill
  most bacteria reaching the lungs

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Special defenses of specific mucosal surfaces

• Eyes
• The most vulnerable site on the outer surface of
  the body
• Tears contain antibacterial substances such as
  lysozyme, lactoferrin, and sIgA
• The washing action of tears also helps to prevent
  bacterial growth

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Special defenses of specific mucosal surfaces

• Intestinal tract
• The acidic environment of the stomach and the
  proteolytic enzymes secreted by gastric cells
  kill many of bacteria that are swallowed
• The contents of both small intestine and colon
  contain a high concentration of bile salts, which
  are detergents that disrupt bacteria membranes
  and are toxic to some types of bacteria small
  intestine is relatively free of bacteria
• In the colon, the flow rate of contents is very
  slow, and bacterial density is great the colon
  is mainly protected by resident microflora

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Special defenses of specific mucosal surfaces

• Urogenital tract
• Normally colonized and protected by a complex
  resident microflora
• A prominent member of the vaginal microflora is
  Lactobacillus, a genus of lactic acid-producing
  gram-positive bacteria that prevent pathogens
  from colonizing the vagina by keeping the pH low
  (around 5)

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Defenses of Tissue and Blood

• Bacteria that overcome surface defenses and reach
  underlying tissue or blood encounter an array of
  interior defenses
• Defenses of tissue and blood is much more likely
  to be accompanied by tissue damage because it is
  difficult to destroy bacteria that are inside the
  body without doing some collateral damage to
  surrounding tissue

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Defenses of tissue and blood

• Constituent, nonspecific defenses
• Transferrin a glycoprotein synthesized by the
  liver, has high affinity for iron, plays an
  antibacterial role by depriving invading bacteria
  of the iron they need for growth
• Phagocytes monocytes, macrophages, and
  polymorphonuclear leukocytes, ingest and kill
  invading bacteria

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Defenses of tissue and blood

• Complement
• Complement is a set of serum proteins that, when
  activated, attract phagocytes to the area of
  infection and facilitate phagocytosis of the
  bacteria
• Opsonization coating the surface of a particle
  in a way that facilitates its engulfment by
  phagocytes is called opsonization

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Defenses of tissue and blood

• Mannose-binding protein
• Mannose is a sugar that frequently found on the
  surfaces of bacteria but not on human cells
• Macrophages that are ingesting and killing
  bacteria produce a cytokine called interleukin-6
  (IL-6), which, in turn, stimulates the liver to
  produce the mannose-binding protein
• Binding of this protein to the surface of a
  bacterium activates complement

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Defenses of tissue and blood

• Inflammation
• The combination of complement activation and
  phagocyte attack on invading bacteria produces a
  condition called inflammation, which is
  characterized by redness, swelling and pain in
  the area of infection.
• The redness and swelling probably result from
  leakage of fluid from blood vessels as phagocytes
  move through the blood vessel wall and into
  tissue
• Pain probably results from local tissue
  destruction

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Defenses of tissue and blood

• Induced defenses antibodies, activated
  macrophages, and cytotoxic T cells

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Defenses of tissue and blood

• Antibodies
• Three types of antibody are important in the
  defense against bacterial infections
  immunoglobulin G (IgG), IgM, and sIgA
• IgG and IgM are the main antibody associated with
  protection of blood and tissue, sIgA is the main
  antibody associated with protection of mucosal
  surface
• IgG is best at opsonizing bacteria, IgM is best
  at activating complement
• In addition, antibodies can bind bacterial toxins
  and prevent them from attaching to host cells by
  covering up toxin sites that would normally bind
  to host cell receptors toxin neutralization

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Defenses of tissue and blood

• Production of antibodies and activation of
  macrophages and cytotoxic T cells
• When bacteria are degraded by macrophages,
  peptide fragments of bacterial proteins are
  transferred to the macrophage surface, attached
  to protein complexes called major
  histocompatibility complexes (MHCs)
• MHC presentation of bacterial antigens results
  either in activation of B cells that produce
  antibodies or activation of special class of T
  cell (cytotoxic T cell) that kills infected host
  cells displaying the same antigen

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Factors that impair or improve host defenses

• Nutrition
• A major factor in maximizing the effectiveness of
  all host defenses is good nutrition
• Malnutrition in children and adults is invariably
  accompanied by decreased resistance to infections
• Cells of mucosal surfaces and the immune system
  are among the most rapidly dividing cell
  populations in human body, a deficient in
  adequate nutrients would have a disproportionate
  effect on these cell types

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Factors that impair or improve host defenses

• Stress
• Stress is clearly an important fact that affects
  the efficacy of host defenses, people living
  under conditionals that induces stress appear to
  be more susceptible to infections, and the basis
  for this is incompletely understood
• Underlying conditions such as cancer, AIDS,
  alcoholism and genetic defects all impair the
  bodys ability to ward off bacterial infections