Digestive system infections:Barriers to infection:1-The stomach acid of a pH less than or equal to 4.2-Shedding of mucosal epithelium lining the alimentary system.3-A variety of local defense mechanisms; mucus formation and gut motility( Peristalsis).

4- The normal flora of intestinal tracts. 5-The glycocalyx (mucin-rich layer) of epithelial-cells surface. (Clostridium difficile produces anti-mucin toxins)

N

6-The Bile salts detergent action.

7-The secreted antimicrobial peptides. (Enterotoxigenic E.coli produces heat-labile toxin that suppress these peptides.

8-M cells of Peyer patches have surveillance function.

9-Secretory IgA.

Establishment of infectious diseases in the digestive system:

The defense barriers are changed in favor of the microbe due to:1-Anatomic alterations: A-Obstructions to the flow of intestinal secretions (gallbladder stones). B-Surgery may create intestinal “blind loops” that are isolated from the moving stream of intestinal contents. Absence of flushing action of intestinal secretions. Bacterial overgrowth syndrome; malabsorption.

N

2-Changes in stomach acidity; due to proton-pump inhibitors: -Decreased pathogenic dose results in colonization of intestinal mucosa; Example Salmonella species. -Shigella species and E.coli O157:H7 are acid resistance.

3-Alterations to the normal flora; due to broad-spectrum antibiotics. Pseudomembrane colitis; Clostridium difficile.

4-Invasion of Gut by virulent microbial strains.

Intestinal invasive diseases , inflammation and damage:

1-Invasive Enteritis, and dysentery (bloody diarrhea): A-Shigella dysenteriae infection:- Pathogenic dose: less than 200 CFU.- Reservoir: human colon only (no animal carriers).- Transmission: Fecal-Oral, Person to Person.

Pathogenesis: - Endotoxin triggers inflammation .

- Shiga toxin type I: Enterotoxic and cytotoxic activities. It is interfering with 60S ribosomal subunit; necrosis .

- The microbe invades the M cell in the lumen of Gut.

N

- Multiply inside these cells, using actin polymerization to infect neighboring epithelial cells.

- Released , engulfed by intestinal macrophages.- Escape from APC, infects other epithelial cells.- Very Shallow ulceration of intestinal mucosa.

N

- Enterocolitis, shigellosis (most severe form is dysentery).

- Fever , lower abdominal cramps; diarrhea first watery,

then bloody with mucus. - Invasive infection: shallow ulcerative Enterocolitis.- Hemolytic-Uremic syndrome.B-Entamoeba histolytica (dysentery).Microbiology:- Gram-negative short bacilli, - Nonmotile, Non-spore formers.

- Enterobacteriaceae grow best on XLD.- Facultative anaerobic, non-Lactose fermenters.- Can not produce H2S and identify by API 20E

2-Invasive Enteritis and Hemorrhagic Colitis: Enterohemorrhagic E. coli:

-Transmission: food (hamburger), milk, Fecal-Oral . -Incubation period: 3-5 days.

-Reservoir: Cattle; bovine feces, pork. -Pathogenic dose: 10-100 CFU .

-Toxin: Verotoxin : Exotoxin -Pathogenesis :

- EHEC bind to cells in the large intestinal mucosa(Caecum,Colon).

- Verotoxin-Epithelial receptor interaction . - Decrease protein synthesis by interfering with 60 S

ribosomal subunit .

N

-Intracellular localization inside lysozyme. -Cell death; apoptosis .

-Mucosal necrosis; Hemorrhagic Colitis with bloody diarrhea .

- Shiga like exotoxins; Hemolytic-uremic syndrome.

Microbiology:-Gram negative short bacilli.-Lactose fermenters.- Metallic green sheen on EMB medium.- Indole positive.

N

3-Invasive Enteritis and Bloody watery diarrhea: A- Campylobacter jejuni infection:Reservoir: intestinal tracts of humans, cattle, sheep, dogs, cats, and Poultry.Transmission :

-Fecal-Oral (direct cont.), Ingestion of contaminated meat ( poultry ,) , contaminate water or unpasteurized

milk .Incubation period :

3-5 days.Microbiology :

Gram-negative curved

helical rods

with polar flagella.

N

- Microaerophilic ( 10% CO2, 5% O2, and 85% N2) microbe

with an optima of 42˚C temp. - Humidity should be > 95%.

- Resistance for Cephalothin. - Sensitive for Nalidixic acid. - Catalase and oxidase positive.

Pathogenesis of Campylobacter jejuni:

Pathogenic dose: as few as 500 CFU. - The microbe invades the small and large intestinal mucosa.- Colonization of intestinal epithelial layer, engulfed by

intestinal dendritic cells(DC).- DC release inflammatory mediators, chemotaxis, cellular infiltration.- Ulcerative, inflammatory lesions in the jejunum, and ileum.- Ulcerative Colitis. - Pus and RBCs in stool; Acute Enteritis (common cause of infectious diarrhea worldwide). - Traveler’s diarrhea and pseudo-appendicitis.

N

n

Infective Ulcerative Colitis and dysentery:n

B-Salmonella enteriditis and Salmonella typhimurium:

Reservoir :-Human: Large intestinal tracts: Carriage state.

-Animals: most important: Chicken .

Transmission :1-Fecal-Oral from carrier person .

2-Ingestion of contaminated chicken products

( raw chicken, eggs.) Incubation period: 6-48 hours.

Pathogenesis:The Microbe invades the ileocecal region lymphoid tissue .

Invasion of Lamina propria; endotoxin activity.

Dendritic cell activation; production of TNF and IL-8 .

PMN cells chemotaxis and PG response .

PG stimulate cellular cAMP of epithelial cells.

Release of NaCl from intestinal epithelial cells; dehydration.

PMN cells prevent mesenteric lymph node and RES invasion.

Bloody watery diarrhea .

Diagnosis :

Clinical: abdominal symptoms and fever .

Laboratory: Stool culture: similar to Salmonella typhi .

C- Listeria monocytogenes :

Associated food and Transmission:-Unpasteurized milk products, undercooked meat & raw

vegetables-Fresh soft cheese.

-Ready-to-eat meat.

Incubation period: 8 - 48 hrs.

Pathogenesis:

Invasion of intestinal epithelium.

Intracellular survival: Listeriolysin-O.

Cell-mediated immunity . Watery bloody diarrhea.

listeriolysin

hostactin

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