Helminth

Question 1

taxonomy of helminths

Answer 1

• nematodes (roundworms)
• platyhelminthes (flatworms)
  
  • trematodes (flukes)
  • cestodes (tapeworms)

Question 2

What is the GI host response to helminths?

Answer 2

• Th2 CD4+ cells
• IL-5 recruiting eosinophils
• IL-4/IL-13 support B cell production of IgE
• effector cells: mast cells, eosinophils & goblet cells

Question 3

Name parts of helminth-induced pathology

Answer 3

• successful parasite lives in host
• disease mostly depends on host factors
• protozoa multiply in host, most others don‘t
• direct tissue destruction
• hypersensitivity reactions common
• eosinophilia

Question 4

Name three intestinal helminths and their related experimental model

Answer 4

• Strongyloides stercoralis - strongyloides ratti
• human hookworm (ancylostoma duodenal) - Nippostrongylus brasiliensis
• Schistosomia spp. - Schistosomia mansoni

Question 5

hookworm model (with life cycle)

Answer 5

• Nippostrongylus brasiliensis
• definitive host: rodents
• not infective for human -> no biosafety level
• life cycle: larvae penetrates skin -> lung -> pharynx -> adults in gut —> eggs in feces

Question 6

How do you get L3 larvae of N. brasiliensis to infect mice?

Answer 6

• propagation in rats (bigger)
• feces is collected an incubated
• infection by s.c.

Question 7

How to analyse N. brasiliensis infection in mice?

Answer 7

• Analysis 7-14 dpi (WT can clear infection completely)
• worm (intestine) and egg (feces) count (eggs flout on surface of buffer)
• staining of intestine
• IgE in serum
• Th differentiation

Question 8

BALB/c vs IL-4Rα-/- mice in n. brasiliensis infection

Answer 8

• BALB/c can clear infection, IL-4Rα-/- are susceptible
• IL-4Rα-/- have reduced Th2 response
• IL-4Rα-/- have reduced levels of IgE in serum

IL-4Rα-/- have no IL-4 and IL-13 and no protection

Question 9

Facts about Strongyloides stercoralis

Answer 9

• 2 unique life cycles (free and parasitic)
• 30-100 million infections annually
• Filiariform penetrates skin (contaminated soil)
• larvae migrate into lung and are than swallowed

Question 10

Pathology of S. stercoralis infection

Answer 10

• invasive: skin penetration
• pulmonary: during migration
• intestine: tissue destruction
• hyperinfections possible (anemia, cough, diarrhea, …)
• can lead to death in immunocompromised individuals

Question 11

Describe the life cycle of S. ratti

Answer 11

females in mucosa of small intestine -> lay eggs -> eggs in feces shed in environment -> hatching
- male develop into free-living adult
- female develop into free-living adult or
- female develop direct into infective L3 larvae

Question 12

How does the S. ratti model work?

Answer 12

• model for S. stercoralis
• not infective for humans
• L3 larvae maintained trough serial passaging
• infection s.c. or percutaneous in buffer drop

Question 13

Detection of S. ratti

Answer 13

• dose dependent
• low (6 larvae) s.c. similar to natural percutaneous route
• egg count via qPCR (28S rRNA)
• adult count in small intestine

Question 14

What is the S. ratti induced immune response?

Answer 14

• nematode specific Th2
• Th1 is reduced

Question 15

Schistosoma spp.

Answer 15

• flatworms
• 4 species
  
  • S. mansoni
  • S. japonicum
  • S. haematobium
  • S. indicum
• Schistosomiasis affects 207 million annually (50% symptomatic)

Question 16

life cycle of Schistosoma spp.

Answer 16

eggs in water -> larvae -> into snail -> larvae in water -> penetrate human skin -> migrate to lymphatic system -> travel to lung (70% are eliminated) -> migrate into liver -> maturation in liver -> migrate into target tissue:
- S. mansoni: mesentric venules of large bowel and rectum
- S. japonicum: mesentric veins of small intestine
- S haematobium: perivesical venous plexus of bladder

50% of eggs stay in tissue, 50% exit body

Question 17

Schistosoma spp. model

Answer 17

• S mansoni -> infectious for human BSL 3
• mince egg containing tissue -> eggs will float on water and hatch
• incubate snails with phototropic miracidia
• keep snails in dark; for cercariae shedding snails in strong light

mice infection via natural route -> place mouse foot in cercariae suspension

Question 18

1. Which Interleukin deficiency enhances mice survival during S. mansoni infection?
2. Which Interleukin deficiency enhances Th1 response?

Answer 18

1.
IL-13

IL-4 induces mortality, same as IL-4-/- IL-13-/- (more eggs in intestine & less in feces)

2. IL-4/IL-13 deficiency, it also diminishes fibrosis