PATHOGENICITY

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PATHOGENICITY

• Chapter 15

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Endotoxins
Figure 15.4b
3
Exotoxin
Figure 15.4a
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Exotoxins

• 3 categories of toxins
• A-B toxins
• Membrane disrupting toxins
• Superantigens
• A-B Toxins
• Part A active enzyme component
• Part B Binding component
• Steps
• Toxin released
• B binds to host receptor and transported to
  cytoplasm
• A inhibits protein synthesis of host and host
  cell dies and B is released from cell
• Example
• Diptheria toxin
• Corynebacterium
• diphtheriae

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Exotoxins

• A-B toxins

Figure 15.5
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Membrane Disrupting Toxins

• Disrupt host plasma membrane lyse the host cell
• Make protein channels in the plasma membrane
• Disrupt the phospholipid bilayer
• Varieties
• Leukocidins
• Target phagocytes
• Protein channels
• Ex. Staphylococci leukocidins
• Hemolysins
• Target RBCs
• Protein channels
• Ex. Stretococci (streptolysin)

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Superantigens

• Invoke very strong immune response
• T cells
• Release lots of cytokines which can cause severe
  symptoms
• Ex. Staphylococci and food poisoning toxins

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Another Way to Classify Exotoxins

• Cardiotoxins attack heart cells
• Neurotoxins attack nerve cells
• Enterotoxins attack the lining of the GI tract
• Cytotoxin attack a wide variety of cells
• Hepatotoxin attach liver cell
• Leukotoxin attacks leukocytes

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More Important Exotoxin Examples

• Botulinum toxin (Clostridium botulinum)--botulism
• A-B Neurotoxin
• Prevents transmission of signal from nerve cell
  to muscle cell at NMJ (inhibits release of
  acetylcholine)
• Tetanus toxin (Clostridium tetani)--tetanus
• A-B Neurotoxin that goes to central nervous
  system
• Prevents inhibition of random contractions by
  muscles
• Cholera toxin (Vibrio cholera)cholera
• A-B toxin enterotoxin
• A induces cyclic AMP formation from ATP
• Causes discharge of many fluids and electrolytes
  from intestine
• Very heat sensitive

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Endotoxin

• Released when gram negative bacteria die and
  their cell walls undergo lysis (after antibiotic
  treatment)
• Cause macrophage to release high levels of
  cytokines
• General Effects
• Endotoxins activate blood clotting proteins which
  blocks capillaries cause clots and death of
  tisse
• Septic Shock loss of blood pressure
• Macrophages release TNF (tumor necrosis factor)
  when they attack some Gram cells
• TNF binds to many tissues of host and may cause
• Damage to blood capillaries (loss of water and
  decrease in blood pressure)
• Damage to blood-brain barrier (leading to
  infection of CNS)

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Pyrogenic Response

• Macrophage ingestion and release of endotoxin
  from bacteria
• Release of interleukin-1(pyrogens) in bloodstream
• Interleukin-1 to hypothalmus and production of
  prostaglandins
• Resetting of bodies thermostat ? Fever

Figure 15.6
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Viruses

• Viruses
• Can penetrate and grow inside of cells where host
  defense cannot get them
• Cytopathic effects visible results of viral
  infection
• Cell death by
• Multiplying viruses
• Inhibition of DNA, RNA or protein synthesis
• Effects on permeability of host membrane
• Cytocidal (results in cell death) vs.
  Noncytocidal effects (cell damage but no cell
  death)
• Macromolecular synthesis to stop
• Lysosome leaking destruction of organelles
• Inclusion bodies (virus parts)
• Syncytium (fusing of cells)
• Change host cell function
• Interferons (protects uninfected cells)
• Antigenic changes on cell surface
• Chromosomal changes cancer causing genes
  activated
• Contact inhibition viruses transform cells into
  cancer causing cells

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Pathogenic Properties of Fungi

• Fungal waste products may cause symptoms.
• May be toxic to human hosts
• Chronic infections provoke an allergic response.
• Proteases enzymes that modify host cell
  membranes to allow attachment of fungi
• Candida, Trichophyton
• Aflatoxin peanut butter can have this
  toxin(normally found growing on grains or other
  plants)
• Produced by Aspergillus

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Pathogenic Properties of Algae

• Paralytic shellfish poisoning
• Dinoflagellates produce neurotoxin called
  saxitoxin
• Mollusks feed on the dinoflagellates
• People who eat the mollusks develop paralytic
  shellfish poisoning

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Portals of Exit

• Respiratory tract
• Coughing and sneezing
• Gastrointestinal tract
• Feces and saliva
• Genitourinary tract
• Urine and vaginal secretions
• Skin
• Blood
• Biting arthropods and needles or syringes

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Mechanisms of Pathogenicity
Figure 15.9