5

Question 1

What is a mucosal surface?

Answer 1

Surface that interacts with air that has associated glands for secreting mucus.
Oral cavity
Respiratory tract
Reproductive/urinary tract
Gastrointestinal tract

Question 2

Defense of mucosal surfaces:

Answer 2

Innate immunity
Adaptive immunity
Nonspecific barrier defenses

Question 3

Transmission of Gram-Negative Mucosal Pathogens

Answer 3

Feces to mouth, via any of the “seven F’s”:
Feces
Food
Fluids
Fingers
Flies
Fomites
Fornication

Question 4

Inoculum Size

Answer 4

For some bacteria, as few as 50-100 organisms is enough to cause disease (e.g., Shigella dysenteriae, EHEC, EIEC)

For other bacteria, millions of organisms are needed to cause disease (e.g., ETEC, EPEC, and Vibrio spp.).

Question 5

Why aren’t we always infected with Gram-negative pathogens?

Answer 5

Natural barrier defenses
Secretory substances
Anatomical and physiological barriers
Indigenous microbiota
Innate Immunity
Adaptive Immunity

Question 6

Natural Barrier Defenses of the Gastrointestinal Tract

Answer 6

Natural anatomical and physiological properties assist with creating a physical barrier
  Acidity
  ranges from pH 1-2 to 9
  Motility
  Mucous layer and underlying glycocalyx
  Tight junctions

Question 7

There is only a single

Answer 7

layer of epithelial cells separating the interior of the body from billions of microbes found on all mucosal surfaces.

Question 8

Lysozyme (a.k.a. muramidase)

Answer 8

Secretory Antimicrobial Compounds

Cleaves β 1,4-glycosidic linkages between N-acetylnuramic acid and N-acetylglucosamine

Question 9

Lactoferrin

Answer 9

Secretory Antimicrobial Compounds

Bacteriostatic effects via sequestering iron

Question 10

Cathelicidin

Answer 10

Secretory Antimicrobial Compounds

Disrupts bacterial membranes of Gm- and Gm+ (as well as fungi)

Question 11

Defensins

Answer 11

Secretory Antimicrobial Compounds

Create pores in microbes (all microbes can be affected)
α-defensins produced by neutrophils and paneth cells (in intestine)
β-defensins produced by epithelial cells

Question 12

How do pathogenic bacteria overcome these innate barrier defenses?

Answer 12

Acid resistance
Fimbriae/Pili
Bacterial structures

Question 13

Acid resistance

Answer 13

Microbes with low infectious dose tend to be acid resistant

Shigella spp. and Enteroinvasive E. coli

Question 14

Fimbriae/Pili

Answer 14

Adhere to tissue to resist being shed

Question 15

Bacterial structures

Answer 15

Gram-negative/Gram-positive cell membrane sensitivities to bactericidal compounds
Cationic amino acids into cell membrane to reduce effects of cationic antimicrobial peptides
Siderophores to sequester iron in low iron environments (e.g., enterobactin produced by E. coli)

Question 16

Macrophages as an Important Component of Mucosal Immunity

Answer 16

Macrophages recognize microbes via pattern recognition receptors. This leads to activation of the macrophages and the ability to kill many microbes.

Question 17

Activation of pattern recognition receptors on macrophages also

Answer 17

initiates the inflammatory response

Question 18

There is a negative side to initiating the inflammatory response at mucosal surfaces!

Answer 18

Inflammatory cytokines, such as TNF-α can disrupt the tight junctions between epithelial cells

Question 19

The densest clusters of lymph nodes are found near

Answer 19

mucosal tissues.

Question 20

The adaptive immune response is generated in the

Answer 20

lymph nodes.

Question 21

Invasive Bacterial Pathogens

Answer 21

Large Intestine
Small Volume of Stool 
Bloody Stool
Leukocytes in Stool
Tissue Ulcerations

Question 22

Toxin-Producing Bacterial Pathogen

Answer 22

Small Intestine
Copious Amounts of Watery Stool
No Blood in Stool
No Leukocytes in Stool
No Tissue Damage

Question 23

“Hybrid” Misfits

Answer 23

Lower Small Intestine/Upper Large Intestine
Colonization causes attaching and effacing lesion
Blood in stool (and possibly in urine with EHEC)

Question 24

Four species distinguished by the O antigen.

Answer 24

S. dysenteriae
S. flexneri
S. boydii
S. sonnei

Subgroups found within each of these.

Question 25

Shigella Entry, Spread, Multiplication

Answer 25

Inoculum size very small Acid resistance facilitates survival through the stomach Acid resistance is controlled by a global regulatory system of genes under the control of RpoS made in the stationary phase. Occurs when Shigella are grown anaerobically Will usually multiply/colonize the colon

Question 26

Invasive Pathogens: Shigella spp.

Answer 26

Mucosal surface is resistant to infection, but basal surface is not Enter M cells, via outer membrane proteins called invasion plasmid antigens Released into lamina propria, ingested by macrophages. Inflammatory response causes illness. Epithelial cells will ingest the bacteria, facilitated by bacterial factors Bacterial proteins lyse the phagosomal vesicle Intracellular spread facilitated by IcsA, an ATPase that causes actin polymerization

Question 27

Damage

Answer 27

An ulcer develops when invaded cells die and slough off Neutrophils can be seen by microscopy in stool samples All species will induce an inflammatory diarrhea with leukocytes in the stool. S. sonnei induces a watery stool (still has leukocytes)

Question 28

Shigella dysenteriae type 1 is different!!!

Answer 28

Gastroenteritis caused by S. dysenteriae type 1 presents as an invasive diarrhea S.dysenteriae type 1 also produces Shiga toxin, Kills intestinal epithelial and endothelial cells Disrupts Na absorption

Question 29

Salmonella

Answer 29

All medically important species belong to S. enterica. S. enterica has multiple subspecies, but medically important subspecies belong to the enterica subspecies. Different serotypes cause different diseases. So, what was once called Salmonella typhimurium is formerly: Salmonella enterica subspecies enterica serotype Typhimurium This is cumbersome! So, convention is to designate it as: Salmonella Typhimurium or S. Typhimurium

Question 30

Salmonella-

Answer 30

Gastroenteritis—Typhimurium and Enteritidis serotypes Focal infection of vascular endothelium—Choleraesuis and Typhimurium serotypes Infections of organ systems—Typhimurium serotype Typhoid fever— Typhi and Paratyphi serotypes

Question 31

Salmonella infection

Answer 31

Fecal (human or animal)--oral transmission Relatively large inoculum required (10-100 million organisms) More acid-sensitive than shigellae Low pH induces the expression of at least 40 proteins found on pathogenicity islands on large virulence plasmids

Question 32

Invasive Pathogens: Salmonella spp.

Answer 32

When organisms approach the cell’s surface, they induce activity of cell signalling pathways, and cause an increase in cellular Ca++ These events induce surface “ruffles” and uptake of the organisms (microbe-directed phagocytosis) Remain within cell vesicles for many hours (unlike Shigella) Organisms released to lamina propria—somehow induces Na Cl loss from the host cells Macs engulf most, but some escape to cause a transient bacteremia --the typhoid serovars will survive and grow within the macrophages

Question 33

Salmonella Typhi

Answer 33

Enters into lymphatic system Replicates within macrophages throughout the body ``` No animal reservoir, strictly a human pathogen Asymptomatic carriers (Typhoid Mary) ``` Carriers have colonized gall bladders and the organisms can be cultured from their feces