Introduction to Host-Microbe Interactions. Normal Flora More bacterial than human cells in the body...
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Transcript of Introduction to Host-Microbe Interactions. Normal Flora More bacterial than human cells in the body...
![Page 1: Introduction to Host-Microbe Interactions. Normal Flora More bacterial than human cells in the body –provide some nutrients (vitamin K) –stimulate immune.](https://reader030.fdocuments.net/reader030/viewer/2022032704/56649d695503460f94a4743d/html5/thumbnails/1.jpg)
Introduction to Host-Microbe Interactions
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Normal Flora
• More bacterial than human cells in the body– provide some nutrients (vitamin K)– stimulate immune system, immunity can be
cross-reactive against certain pathogens– Prevent colonization by potential pathogens
(antibiotic-associated colitis, Clostridium difficile)
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Potential Colonization Sites
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Types of Pathogens
• Primary Pathogens– Cause disease upon infection, not normally
associated with host• Plague (Yersinia pestis), influenza virus
• Opportunistic Pathogens– Cause disease under some circumstances,
sometime members of normal flora• Pseudomonas, Candida albicans
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Progression of Disease
• Transmission: infectious dose from 10-106 organisms
• Incubation period: few days (common cold)-weeks (hepatitis A)-months (rabies)
• Convalescence: – Clearing (Strep throat, S. pyogenes)– Latency (Chicken pox, tuberculosis, cold sores)
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Koch’s Postulates• Proposed by Robert Koch• Conclude that a microbe causes a particular
disease• Must fulfill four postulates• 1. Microorganism must be present in every
case of the disease• 2. Organism must be grown in pure culture
from disease hosts• 3. Produce the same disease from the pure
culture• 4. Organism recovered from experimentally
infected hosts
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Molecular Postulates• Describe virulence factors
• Four postulates
• 1. Virulence gene or its product must be present
• 2. Virulence gene must transform a non-pathogen into a pathogen
• 3. Virulence gene must be expressed during disease process
• 4. Antibodies against gene products are protective
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Establishing an Infection
• 1. Encounter: – fecal-oral (cholera)– human-human (tuberculosis)– animal-human (rabies)– vector-borne (plague, lyme disease)– environmental contact (anthrax)
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Establishing an Infection
• 2. Adherence– Prevents early clearance– Often bind host tissues via pili– Specificity can determine host range of
pathogen
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Establishing an Infection
• 3. Colonization: multiplication and maintainance– Competition with normal flora– Resist:
• bile
• stomach acid
• peristalsis
• skin secretions
• IgA (mucosal antibodies)
• compete with host for iron
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Establishing an Infection
• 4. Molecule Delivery– Affects target
cell structure and host response
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Invasion:Breaching Anatomical Barriers
• Find new niche with few competitors
• Gain access to rich nutrient supply
• 1. Skin: tough barrier, rely on wounds or insect vectors
• 2. Crossing mucous membrane (e.g. intestinal epithelial cells)
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Zippering-model of invasion
Tight ligand-receptor interactions direct uptake
“one at a time” uptake
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Ruffling method of invasion
General induced cellular response
Can lead to co-invasion of other bacteria in close proximity
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M cell Invasion
• M cells are a portal to the immune system
• Important site of “antigen sampling”
• Some pathogens use phagocytic nature of M cells to access deeper tissues by transcytosis
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Avoiding the Host Defenses
• 1. Hiding within host cells– Avoid exposure to host antibodies if remain
intracellular– Access to rich source of nutrients
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Cell-to-cell Spreading
Shigella and Listeria species lyse out of vacuole
-assemble actin at pole-actin propels them into neighboring cell
“convergent evolution”
“molecular mimicry”
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Avoiding the Host Defenses
• 2. Avoiding complement killing– Complement factors in blood serum can assemble
into MAC “membrane attach complex” that are bactericidal
– C3b is first component of complex to bind– Some bacteria bind factors that regulate C3b
activity, prevent MAC assembly• “serum-resistance”
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Avoiding the Host Defenses
• 3. Avoiding phagocytosis
– Innate immune cells engulf (phagocytose) and kill microorganisms with degradative enzymes
– Block signaling molecule production or degrade them after production
• C5a cleaved by C5a peptidase of Strep pyogenes (strep throat)
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Avoiding the Host Defenses
• 3. Avoiding phagocytosis
– Capsule production on surface of bacteria: capsule leads to C3b inactivation-”serum resistance”
– M protein of Streptococcus: also inactivates C3b– Fc receptors: bind antibodies and orient dangerous end
away from bacteria• Found in Streptococcus (Protein G) and Staphylococcus
(Protein A)
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Survival Strategies within Phagocytes
• A niche without competitors
• Phagosomal escape: lyse out of vacuole and grow in cytoplasm of host cell– Shigella and Listeria
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Survival Strategies within Phagocytes
• Blocking lysosomal fusion: prevent delivery of degradative enzymes to bacterial compartment– Mycobacterium (tuberculosis)– Salmonella (food poisoning or typhoid fever)– Legionella (Legionnaire’s disease)
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Survival Strategies within Phagocytes
• Surviving lysosomal fusion:
– Coxiella– Legionella
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Avoiding Antibodies
• 1. IgA protease: cleaves Ab’s found in mucosal secretions (Neisseria gonorrhoeae)
• 2. Antigenic variation: turning pili On and Off, or switching to new pilus
• 3. Mimicking the host: look like self-antigens– Streptococcus pyogenes has capsule of
hyaluronic acid, also made by host tissues
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Damage to Host (Disease)• 1. Exotoxins
– May require prior colonization (cholera)– May cause food poisoning even in absence of
organism• Botulism or Staphylococcus aureus toxin
– Immune system often target toxin for neutralizing Ab’s
• Vaccine against toxin
– A-B toxins: A is catalytic subunit, B binds host cells
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Damage to Host (Disease)
• 2. Membrane-damaging toxins – Hemolysins
• Cause cell-lysis: Streptolysin O
– Phospholipases• Cleave lipids in membranes: Clostridium perfringens
– Gas gangrene
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Damage to Host (Disease)
• 3. Superantigens – Hyperstimulate the immune system
• 1/5 T cells stimulated rather than 1/10,000
• Fever, nausea, diarrhea, vomiting
– Leads to shock• Organ failure, circulatory collapse
– Cause of toxic shock syndrome (TSST)• Staphylococcus aureus and Streptococcus pyogenes
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Damage to Host (Disease)
• 4. Endotoxins (attached to cell)
– LPS, in the outer leaflet of Gram negative bacteria
• Lipid A is toxic if organisms enter bloodstream– Massive immune cell infiltration
– Activation of coagulation
• Intravenous fluids are screened for Lipid A
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Damage due to the Immune System
• Inflammation: bacterial meningitis– Neisseria meningitis
• Antigen-Ab complexes– Settle in kidney or joints
• Glomerulonephritis from S. pyogenes
• Cross-reactive Ab’s– Ab’s against pathogen may cross-react with host
tissues• Accute rheumatic fever, complication of Strep throat
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