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Pathogenesis
- A microbe capable of causing disease is a pathogen
- Virulence: measure of pathogenicity (in terms of degrees)
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How Do Microbes Make us Sick?
- Many microbes have to gain access to host
- Cause damage to host tissues
- Sometimes microbial wastes cause disease
- Some microbes don’t need to enter to cause disease (e.g. dental caries, acne)
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Portals of Entry
- Ways to get inside host
- Mucous membranes
- Skin
- Parenteral route (under the skin)
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Mucus membranes
- Respiratory tract
- Gastrointestinal tract
- Genitourinary tract
- Conjunctiva (in eye)
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Respiratory Tract
- Preferred Site
- Easiest Portal of Entry
- Inhalation of dust/droplets
- Common cold, pneumonia, tuberculosis, influenza, measles, smallpox
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Gastrointestinal Tract
- Food/water contamination
- Contaminated fingers
- HCl/bile/enzymes take care of most microbes
- Some survive
- Poliomyelitis, shigellosa, cholera
- Pathogens are eliminated in feces
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Genitourinary Tract
- Sexually transmitted diseases
- Some can penetrate unbroken membranes
- Others require an opening
- HIV, HPV, chlamydia, Herpes, syphilis, gonorrhea
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Conjunctiva
Conjunctivitis, trachoma, opthalmia neonatrium
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Parenteral Route
- Punctures
- Injections
- Bites
- Cuts
- Wounds
- Surgery
- Split skin
- HIV, Hepatitis, Tetanus, Gangrene
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Pathogenicity
- Depends upon:
- Portal of entry
- Number of microbes introduces
- Type of microbe introduced
- ID50
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ID50
- Infectious dose for 50% of a sample population
- Comparative value
- E.g: Bacillus anthracis
- Subcutaneous: ID50=10-50 endospores
- Inhalation: ID50=10,000-50,000 endospores
- Gastrointestinal tract ID50=250,000-1 million endospores
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LD50
- Potency of a toxin
- Lethal dose
- Botulinum toxin LD50=0.03 ng/kg
- Shiga toxin LD50=250 ng/kg
- Staph enterotoxin LD50= 1350 ng/kg
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Adherence
- How microbe binds to host cells to gain access
- Adhesins(ligands)/receptors
- Pathogen/host
- Adhesins are found on glycocalyx, pili, fimbrae, flagella (all bacterial)
- Most studied to date are glycoproteins or lipoproteins
- Bind to sugars on the surface of hosts (e.g. mannose)
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Adherence
- Treponema pallidum (clamydia)
- Tapered end
- Corkscrew motion
- Can make it’s way through mucous membrane. Doesn’t have to go through broken cells because of the specific shape.
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Biofilms
- Contact lenses
- Catheters
- Stents
- Heart valves
- Hip replacement components
- Estimate is that ~65% of human bacterial infections are due to biofilms
- Biofilms stick bacteria to surfaces and resist antibiotics/phagocytosis
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How Bacterial Pathogens Penetrate Host Defenses
- Capsule
- Cell wall components
- M protein
- Opa
- Mycolic acid
- Enzymes (exoenzymes)
- Coagulases
- Bacterial kinases (fibrinolysin)
- Hyaluronidase
- Collagenase
- IgA proteases
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Capsules
Capsules prevent phagocytes attaching to bacteria
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Resistance
- Some bacteria can live inside phagocytes without being digested!
- Enzymes can help bacteria resist phagocytosis
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IgA proteases
- Imunoglobulin (antibody)
- IgA Abs present on mucosal surfaces
- IgA proteases cleave antibody
- Inactivating it
- Line mucous membranes. They are there to grab. It is a way for macrophages to see the pathogen. Some pathogens can break this apart. It makes the pathogens form a glob which makes it easier to see.
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Invasins
- Surface proteins
- Rearrange actin filaments of host cytoskeleton
- Membrane ruffling
- Microbe sinks or is engulfed by host cell
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Antigenic Variation
- Influenza (antigenic shift)
- N. gonorrhoeae
- Trypanosoma brucei gambienese
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