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Pathogen Invasion
Chapter 24
18
Biology
Professional
02/24/2012

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Term
What must a pathogen do to be considered "invasive"?
Definition
Penetrate epithelium on its own. It may stop directly after.
Term
Which invasive pathogens are found in the respiratory tract?
Definition
1) Rhinovirus (non-enveloped ssRNA+ picornavirus)- STOP THERE

2) Influenza (segmented, enveloped, ssRNA- orthomyxovirus) STOP THERE

3) Measles, VZV and TB invade further.
Term
Which invasive pathogens are found in the Urogenital tract?
Definition
1) HPV-6 (non-enveloped, circular Papova dsDNA virus) STOP THERE

2) Chlamydia spp. (gram - atypical bacteria) STOP THERE

3) HSV 1 and 2 and Syphillis will invade further
Term
Which invasive pathogens are found in the Skin?
Definition
1) HPV 1, 2 and 4 (non-enveloped, circular Papova dsDNA virus) STOP THERE

2) S. aureus will go deeper
Term
Which invasive pathogens are found in the GI tract??
Definition
1) Shigella spp. (Lac-, H2S-, gram - enterobactericiaceae) STOP THERE

2) Rotavirus (un-enveloped, dsRNA virus) STOP THERE

3) Salmonella typhi and Piliovirus will invade further
Term
True or False.

E. coli is not an invasive pathogen
Definition
False!

EHEC and EIEC are invasive species of E. coli.

EPEC, EAEC and ETEC and non-invasive
Term
True or False:

Symptoms of pathogens that stop after invading the epithelium arise faster than those associated with systemiically-invading pathogens?
Definition
True

STOP fast at a red light
Term
How do non-viral pathogens enter epithelial cells?
Definition
Pathogen-directed endocytosis with "cross-talk"
Term
What clinical symptoms does a Y. enterocolitical infection cause?
Definition
GI disease (enterobacteriacae/gram negative, oxidase- rod), including fever, cramps and diarhea.
Term
How does Y. enterocolitica invade epithelial cells?
Definition
Remember Invasin, B1-integin/M-cell, YOPs, LPS and Zipper

3 genes are critical (can give E. coli invasive ability)

1) Following ingestion, binding of "invasin" (only produced at low temperatures) on pathogen to beta-1 integrin on M cells of colon leads to "zipper" adhesion.

2) After endocytosis, Y. enterocolitca enters subepithelial tissue of Peyer's patches (spread to LN if patient in immunocompromised)

3) Cause fever with LPS and resist phagocytosis with YOPs
Term
How does Y. enterocolitica relate to E. coli invasiveness?
Definition
1) Transformation with any one of 3 genes on Y. enterocolitica that enable invasion will imbue E. coli with this ability.
Term
How does Shigella/Salmonella invade intestinal epithelial cells?
Definition
Remember, 30 genes, Mix-Spa proteins/TTSS (III), IpA, IscA/B, LPS and Shiga toxin

1) Following ingestion, body temp triggers expression of TTSS (III) and IpA

2) TTSS transfers IpA out of pathogen, where it then binds to M cells and causes membrane ruffling

3) Pathogen is taken up by macropinocytosis into M cell where it kills initial macrophages

4) IpA enable pathogen uptake into colonocyte cytoplasm, where they begin multiplying and migrating (IscA-mediated)

5) Interactions with macrophages lead to TNF-a, PMN recruitment, which along with Shiga toxin cause inflammation (in dysenteriae only)

6) At basolateral side of colonocyte, pathogen can get to next colonocyte via IscB-mediated transport (avoid extracellular space)

7) Death may occur from electrolyte-fluid imbalance!
Term
What are the roles of IpA, IscA, IscB and LPS in Shigella pathogenesis?
Definition
IpA- membrane-ruffling and pathogen uptake

IscA- pathogen movement through colonocyte cytosol with actin-cytoskeletal interactions

IscB- Direct transfer of pathogen from basolateral side of colonocyte to next colonocyte without exposure to extracellular environment.

Shigella toxin- inflammation in S. dysentariae
Term
What are the primary differences between Shigella and Salmonella invasion/pathogenesis?
Definition
1) Shigella uses plasmid-encoded "invasion genes" and is free in the cytoplasm of coloncytes (only M cells)

2) Salmonella uses chromosomal-encoded "invasion genes" and is found persistently in endosomes (M cells and enterocytes)
Term
What does the presence of fecal leucocytes indicate?
Definition
That it was an INFLAMMATORY, invasive intestinal infection
Term
How can you distinguish between the different species of Shigella?
Definition
Biochemical reactions and by O antigens

S. sonnei is common in US and S. dysenteriae is most serious (Shiga toxin)
Term
What are the important biological characteristics that define Shigella?
Definition
1) Gram-negative, oxidase-negative rod that is a facultative anaerobe.

2) Non-motile and cannot make H2S (different from Salmonella)

3) Human reservoir and EXTREMELY VIRULENT (resistance to gastric acid)
Term
What treatment/prevention methods are available for Shigella infection?
Definition
1) Hygiene

2) Antibiotics for severity of symptoms

3) Dont use anti-intestinal mobility drugs!
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