immunology exam 1

families under order cyclophylidea

• taenia solium (pork tapeworm)

• taenia saginata (beef tapeworm)

• Echinococcus

• Hymenolepis nana

families under order pseudophyllidea

• Diphyllobothrium latum

• human sparaganosis

domain for cestodes and trematodes

eukarya: membrane bound organelles

kingdom animalla

• lack of cell wall

• multicellular

• locomotion

• heterotrophs: can’t produce own food

• usually has sexual reproduction

phylum platyhelminthes

(flatworms)

• self fertilization

• parenchyma in body cavity

• ladder like nervous system

• flame cells (excretion and osmoregulation)

phylum platyheminthes classes

• Turbellaria (mostly free living)

• trematoda

• monogenea

  • fish ectoparasites

• cestoda (tapeworm)

subclass digenea

• digenetic trematodes

• flukes

• lifecycle

  • at least 2 hosts

  • DH + snail IH

  • maybe more IH

• economic losses

• medical importance

generalized life cycle of trematodes

1. eggs passed in feces

2. eggs in water

3. miracidia hatch from eggs, sneak out snail IH

4. miracidia penetrate snail IH

   1. sporocyst

   2. rediae

   3. cercariae

5. free swimming cercariae encyst on aquatic vegetation

6. metacercariae on vegetation ingested by DH

7. immature flukes

8. adult flukes

trematodes metamorphosis

• cercariae → adult worm in DH

• cercariae → metacercariae → adult worm in DH

• egg (released by DH) → miracidium → sporocyst

trematodes asexual reproduction

• sporocyst → secondary sporocyst

• sporocyst → rediae → secondary rediae

• polyembryony formation of >1 embryo from a single fertilized ovum or in a single seed

polyembryony

• formation of >1 embryo from a single fertilized ovum or in a single seed

trematodes sexual reproudction

adult worm in DH → egg

trematodes morphology

• lack circulatory, skeletal, and respiratory systems

• parenchyma

• ventral sucker

• digestive tract

• nervous system

• tegument

parenchyma

• fills space between body wall and guy

• attachment points

• passage of materials

trematode digestive tract

• mouth surrounded by oral sucker

• pharynx

• esophagus

• cecum

cecum

• bifurcates

• unbranched/ branched

• blind

mouth surrounded by oral sucker

pharynx

espohagus

Trematode Nervous system

• cerebral (brain ganglion)

• nerve chords

• sensory endings

  • chemoreceptors

  • tangoreceptors

Brain ganglion

anterior nerves

nerve cords

center to outer: ventral dorsal lateral

trematode reproduction

• monecious: except schistosomes

  • both ovaries and testes

• can self fertilize

• mainly cross fertilize

vitellaria

testes

seminal receptable

ovaries

uterus

Tegument

• synctium

  • function

    • hydrolytic enzymes: defesnes

    • muscles: movement

    • materials: in and out

synctium

mutlinucleated tissue with no cell boundaries

inside DH

1. intestinal flukes: only in intestine

2. liver flukes

3. lung flukes: only in lungs

4. blood flukes

Trematode Egg morphology

• operculum (not in all species)

• viscous cushion

• developing miracidium

• vitelline membrane

operculum (not in all species)

viscous cushion

developing miracidium

vitelline membrane

shell

miracidium morphology

100 um

• sensory papilla

• cephalic ganglion “brain”

• cilated epidermal plate

• apical gland

• lateral gland

sensory papilla in miracidium

• photoreceptors

• georeceptors

• chemoreceptors

Miracidium behavior

• find and infect snail within 24 hours

miracidium host finding (environmental cues)

• or - to light, gravity, temp

• snail hosts → similar responses

  • parasite goes to same location as hosts

miracidium host finding (host cues)

→ miraxone: snail chemicals (amino acids, fatty acids, NH3)

→ attract miracidia

miracidia attraction measured by

• rate of change of direction (RCD)

  • far from snail: fast swimming and lower RCD

    • moves to other spaces

  • close to snail

    • increase RCD and slow swimming

    • stays close to host

• swimming speed

miracidia infection of snail

• respond to components of snail mucus

• wrong cues → leave

• correct cues → penetrate snail

• inside snail → metamorphis

sporocyst and redia

• loses cilia

• new tegument

  • microvilli

    • absorption

• no mouth/ digestive system

• geminal sac embryos

  • daughter either secondary sporocyst of rediae

    • become cercariae

primary sporocyst

• germ balls at different stages of development

• secondary sporocyst inside

redia

• rudimentary area

  • gut

  • germ ball

  • ambulatory bud

• also has

  • mouth

  • pharynx

  • glands

  • collar

  • birth pore

effects of sporocysts and rediae on snail host

• parasitic castration

  • bigger snail → more space and tissue

  • ex: redia move to reproductive structures

    • feed on and destroy tissue

  • ex: hormone manipulation

    • schistomomin

      • small peptide hormone → normal reproduction

      • larvae stimulate overproduction

        • inhibits snail reproduction

cercaria morphology

head and tail

cercaria behavior

a. exit snail

• escapes glands (enzymes)

• external environment

  • short lived (1-3 days)

  • swim/crawl → encyst / infect host

cercarie development pathways

• encyst on vegetation → metacercaria

• penetrate 2nd IH → metacercaria

• penetrate DH → adult worm

cercaria: species which encyst on plants

• in water → find plant

• post acetabular glands produce mucus

  • attach to plant

• shed tail

  • cystogenous glands

  • produce metacercaria

species that infect 2nd IH and DH

• in water → find suitable host

  • spatial location

    • light, gravity, temp, host cues

      • same location as host

  • temporal location

    • circadian release

      • same time as host

• infection of host

  • mucous glands → attachment

  • sheds tail

  • penetration glands

    • enzymes → digest tissue

cercariae that infect 2nd IH inside host

• cystogenous glands → metacercariae

cercaria infects DH inside host

migration in host → adult worm

cercarial success (not all make it)

• schistosomes

  • many species → east host is specific

    • bird schistosomes

      • cercaria seek bird in water, however bird signals are similar to humans (movement, shadow, warmth, skin chemicals)

    • cercariae penetrate human → wrong host → cercariae dies

metacercaria

1. transmission stage

2. multilayered cyst wall

   1. species that encyst on vegetation: thick and complex

   2. species that encyst on 2nd IH: thin and simple

3. inside DH

   1. responds to complex stimuli

   2. excysts

   3. develops into adult worm

trematode generalized life cycle

1. eggs are passed in feces

2. eggs in water

3. miracidia hatch from eggs and seek out snail intermediate host

4. miracidia penetrate snail intermediate host

   1. sporocyst → rediae → cercariae

5. free swimming cercariae encyst on aquatic vegetation

6. metacercariae on vegetation ingested by definitive host

7. immature fluke

8. adult fluke

how foodborne diseases are passed through food ingestion

• pathogen / parasites

• biotoxins

• chemicals

foodborn trematode infections

1. larval stage in food

2. zoonotic infections

3. domestic or wild animals

4. human replaces DH in lifecycle

distribution of foodborn trematodes

• east asia

• south america

prevalence of foodborn trematodes

• 2 millions DALYs/yr

• >7000 deaths/year

Clonorchis sinesis and opisthorchis viverinni lifecycle differences from the general life cycle

1. snail eats egg

2. miracidia develop inside the intermediate host

3. 2nd IH is a freshwater fish

4. DH (piscivores)

   1. reservior hosts

      1. non-human DH

      2. source of infection

5. adults live in bile duct

clonorchis sinesis

oriental liver fluke

opisthorchis viverrini

cat liver fluke

clonorchis sinesis egg morphology

• 30 × 15 um

• operculum

• shoulders

• abopercular knob

clonorchis sinesis adult morphology

• 2 x .5 cm

• branched testes

clonorchis sinesis pathology

1. adults in bile duct destroy lining

2. damage depends on intensity of infection

   1. < 100 worms → asymptomatic

   2. 100 - 1000 → nausea, diarrhea, pain

   3. > 1000 → fever, pain jaundice

      1. thickening and blockage of duct

      2. hepatomegaly

         1. liver enlargement

      3. cholangitis: inflammation of duct

opisthorchis viverrini difference in morphology

1. has lobed testes compaired to clonorchis sinesis which has branched testes

Clonorchis sinesis and opisthorchis viverinni diagnosis

• detect fibrosis by ultrasound

• detect eggs in feces

cholangiocarcinoma (CCA)

• cancer in the bile ducts

• mainly due to opisthorchis viverrini

reasons for cholangiocarcinoma due to o. viverrini

1. mechanical injury: oral and ventral suckers damage duct epithelium

   1. lesions and ulcers

   2. eggs trapped in ulcer → inflammation

2. toxic metabolic secretions

   1. mitogenic → stimulate host cell proliferation and cancer

   2. may induce transcriptional changes in host cells

3. immunopathology

   1. NO released by immune cells because parasite antigens

   2. excess NO may be mutagenic and inhibit DNA repair

Fasciola hepatica

• sheep liver fluke

• in cattle and sheep

• liver rot

• humans

  • 2-17 million cases worldwide

  • rare in US

Fasciola hepatica life cycle

• same as the general life cycle

• DH/ reservoirs: cattle, sheep, humans

• inside DH

  1. metacercaria excysts in SI and juvenile penetrates intestinal wall

  2. migrates through abdominal cavity

  3. penetrates Glison’s capsule

  4. juveniles develop in liver → liver rot

  5. migrate to bile duct → adults

Fasciola hepatica adult morphology

3 × 1 cm

highly branched cecae

highly branched testes

“shoulders”

Fasciola hepatica eggs morphology

140-75 um

operculum

diagnosis

• eggs in feces (sheep, cattle, humans)

pathology of Fasciola hepatica (migrating juveniles)

• ulcers in eptopic (wrong) sites

  • brain, eyes, skin

pathology of Fasciola hepatica ( juveniles in liver )

• acute fascioliasis (around 8 weeks)

  • necrosis: tissue death

  • hepatomegaly: capsule may rupture

pathology of Fasciola hepatica ( adults in bile duct )

• chronic fascioliasis (> 12 weeks)

  • blockage of bile duct

  • proline secretion: collagen and fibrous tissue in duct walls

  • back pressure → liver atrophy → cirrhosis

paragonimus westermani (oriental lung fluke)

• 2nd IH is crustaceans

• DH: humans

• eggs found through sputum or feces

• inside DH

  • first step same as fasciola hepatica - metacercaria excysts in SI and juvenile penetrates intestinal wall

  • penetrates through diaphragm

  • develop in lungs

paragonimus westermani adult morphology

1 x .07 cm

red/brown

paragonimus westermani egg morphology

100 × 50 um

operculum

paragonimus westermani diagnosis

• eggs in sputum (anything coughed up)

paragonimus westermani pathology (migrating juveniles)

• ulcers in ectopic sites

• brain eyes skin

paragonimus westermani pathology (acute)

cough, pain

paragonimus westermani pathology (chronic)

• may mimic bronchitis or tuberculosis

• blood tinged sputum

praziquantel (PZQ)

• 1970s

• wide range of platyhelminths

  • clonorchis, opisthorchis, paragonimus

• very safe

• exact mode of action unclear

exposure to PZQ

• rapid, sustained muscular contraction

  • paralysis → worm can’t attach

• tegumental disruption

  • exposure of antigens on worms surface

PZQ effects can be linked to

• disruption of voltage gated Ca 2+ channels in tegument

  • rapid influx of Ca2+

    • disruption of functions

treatment for fasciola hepatica

• PZA does not work

• triclabendazole (TCBZ)

  • damage to: tegument (ion pumps), mitochondria, microtubules

control strategies for food born trematoda

• kill adult worms: medicine, PZQ

• reduce environmental contamination

  • sanitation

  • don’t use night soil (human feces)

• snail control

• control reservoir hosts

Snail control

1. physical removal: expensive

2. molluscicides: copper sulfate or sodium pentachlorophenate

   1. ecotoxicity

3. difficulties

   1. recolonization

   2. self fertilizing

control for C. sinensis and o. viverrini

• no nigh soil in fish farming ponds

• proper prep of fish

control for fasciola hepatica

• boil vegetables that grow in water

paragonimus westermani

• properly prep 2nd IH

• avoid drunken crab

• avoid medicinal crab juices

schistosomiasis (snail fever)

• blood flukes

• 200 million infections worldwide

• 3rd only malaria and hookworm

• mainly in Africa, south america, asia

schistosome life cycle difference from trematodes

• no metacercaria or redia

• cercariae infects DH

• cercariae penetrates through skin

• in DH

  • cercariae lose tails during penetration and become schistosomulae

  • circulation

  • migrate to portal blood in liver and mature into adults

  • paired adult worms (male and female)

    • migrate to

      • S.mansoni and S. japonicum in mesenteric venules of bowel/rectum (laying eggs that circulate to the liver and shed in stools)

      • s. haematobiumL in venous plexus of bladder

difference between schistosomes and other trematodes

• dioecious

• live in blood vessels

• non-operculated eggs

• no redia (larval stage in snail)

• no metacercaria

• not food borne