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Evading or Surviving Phagocytosis
- Avoid contact
- Kill the phagocyte
- Survive phagocytosis
- Escape endocytic vesicle
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Kill the Phagocyte
- Gm+ lysins (pop a hole in something else)
- Streptolysin O, S
- Leukocidin (enzyme that targets WBCs)
- Cause leakage of lysosomal enzymes with cell
- Gm- exotoxins
- Adenylate cyclases decrease phagocytic activity
-
Survive Inside Phagocytes
- Mycolic acid (obligate intracellular parasites)
- The liquid on them keeps them from being digested
-
Escape the Phagosome
Phospholipase
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How Pathogens Damage Host Cells
- Use Host Nutrients
- Causing Direct Damage @ site of invasion
- Toxin Production
- Inducing Hypersensitivity Reactions
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Using Host Nutrients
- Many pathogens need Fe (cofactor for a lot of enzymes)
- Fe tied up in lactoferrin, transferrin, ferritin, Hb (Take in iron but they give it away)
- Receptors for Fe-protein complexes
- Siderophores (Iron scavenger-grabs the iron and its gone. It keeps it)
- Siderophore receptor
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Direct Damage
- Proliferation of pathogen in host
- Host cell ruptures
- Buildup of wastes
- Host cell dies
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Production of Toxins
- Toxigenicity: ability of microbe to produce toxin
- Toxemia: presence of toxin in blood
- Gm+/Gm- both produce soluble toxins during exponential growth
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Toxins
- Proteins: Exotoxin (secreted/external to bacteria)
- Lipids: Endotoxin (part of the bacteria)
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Exotoxins
- Secreted proteins
- Similar to enzymes:
- Proteins
- Denatured by pH, temp, chemicals
- Specific
- High catalytic activity/turnover
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3 Categories of Exotoxins
- A/B proteins
- Membrane-Disrupting
- Superantigens (force the cell to mount a huge response)
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A/B Proteins
- These have two parts:
- A: activity
- B: binding (on outside)
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Diseases of A/B Protein Toxins
- Anthrax
- Botulism
- Cholera
- Diptheria
- Tetanus
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Membrane Disruption
- Lyse plasma membrane
- Form channels (pore) Remove contents
- Disrupt phospholipids
-
Membrane Disruptors
- Channel formers
- Leukocidin
- Hemolysins
- Streptolysin
- Phospholipid disruption
- Clostridium
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Superantigens
- Antigens that provoke a huge immune response
- Stimulate T cell proliferation (secretes the cytokines)
- Release cytokines
- Fever
- Nausea
- Diarrhea
- Vomiting
- Shock (loss of blood pressure)
- Death
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Toxins and enzymes produced by S. aureus
- Enterotoxin
- Superantigen
- Beta Hemolysin
- Leukocidin
- Coagulase
- Hyaluronidase
- Exfoliatin
- fibrinolysin
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LPS
- Gm-
- Lipid A
- Released during replication or death
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