Schistosomes

Question 1

Modified Type 2 Response

Answer 1

A mix of a strong type 2 dominated response and a regulatory response in helminth infections

Question 2

Potential roles for the modified type 2 response

Answer 2

I. Wound healing
II. Restrict the level of reinfection/establishment of new worms
III. Kill and/or isolate tissue-damaging life cycle stages
IV. Restrict the level of Th1-mediated inflammation to the parasites in order to limit immunopathology

Question 3

Basic Schistosome Lifecycle

Answer 3

Eggs
Miracidia (snail)
Cercariae (human)
Schistomulae
Adult worms

Question 4

Granuloma components

Answer 4

Lymphocytes
Eosinophils
Macrophages
Fibroblasts (=fibrosis)

Question 5

Pathogenesis of S. haematobium

Answer 5

Ureter and bladder disfunction
Increased risk of bladder carcinoma
Eggs lodged - infertility, bleeding, risk of HIV

Question 6

Egg granuloma over time

Answer 6

Miracidiae insides the egg dies
Granuloma dissolves
Fibrosis remains

Question 7

Function of the T-cell mediated granuloma

Answer 7

Protects the host tissue from toxic egg products and rapid death as seen in T cell-deficient mice

Question 8

What stimulates the Th2 response?

Answer 8

Presence of schistosome eggs

Question 9

Th2 cytokines involved in granuloma formation

Answer 9

IL-4 and IL-13

Question 10

Cytokine that fibrosis in granulomas are dependent on

Answer 10

IL-13

Question 11

Regulartion of schistosome granuloma

Answer 11

IL-13 Rα2
IFN-γ/IL-12
M2 macrophages (AAM)
IL-10

Question 12

IL-13 Receptors

Answer 12

IL-4Rα/IL-13Rα1

IL-13 Rα2

Question 13

Key control mechanism of hepatic fibrosis

Answer 13

IL-13 Rα2 (IL-13 decoy receptor)

Question 14

SM2

Answer 14

Genetic locus associated with familial distribution of hepatic fibrosis and portal hypertension
Influences sever liver fibrosis

Question 15

IFN-gamma Regulatory Role

Answer 15

Polymorphisms associated with severe hepatic fibrosis in S. mansoni

Question 16

Polarisation to Th1 response

Answer 16

No inflammation and rapid death

Question 17

Polarisation to Th2 response

Answer 17

Fibrosis and increased mortality

Question 18

Properties of M2 Macrophages

Answer 18

• Induced by IL-4 and IL-13
• Generate low levels of toxic radicals (nitrogen and oxygen intermediates)
• Express Arginase-1, Mannose Receptor, Fizz-1, YM-1
• Marked anti-proliferative properties
• Secrete anti-inflammatory cytokines, IL-10 and TGF-β
• Produce matrix proteins

Question 19

How do M2 cells regulate granuloma size?

Answer 19

By suppressing Th2 cytokine production and T cell proliferation

Question 20

IL-10 involvement in granulomas

Answer 20

Associated with reduction of granulomatous pathology

Inhibits fibrosis

Question 21

Cytokines associated with resistance to schistosome re-infection

Answer 21

High IgE and low IgG4 against worm antigens

High IL-4 and IL-13 levels

Question 22

IgG4 involvement in parasite control

Answer 22

May block IgE binding to schistosomula and subsequent recruitment of eosinophils
Negative impact on parasite resistance

Question 23

Sm1 gene

Answer 23

Co-dominant gene that controls the level of Th2 responsiveness, and ratio of Th2:Th1 cytokines

Question 24

What does Sm1 encode?

Answer 24

Evidence of an association with an increase in IL-13 expression

Question 25

Three suggested types of schistosome vaccine

Answer 25

1) a prophylactic vaccine to prevent or reduce infection and indirectly transmission 2) a vaccine to reduce or eliminate re-infection intensity or transmission force by reducing female worm survival or egg production 3) a therapeutic vaccine to reduce disease but not affect infection or transmission