Immunity to schistosomes

1. Miricidia in the water, infect snails

2. in snails turn into sporocysts

3. cerceriae into the water

4. cercariae penetrate skin and lose tails

5. when they lose tails they turn into schistosomulae

6. schistosomulae circulate to the portal blood in the liver and mature

7. The paired adults migrate

 a. Mansoni and japonicum migrate to the bowel and released in faeces

 b. haematobium migrate to the venous plexus of the bladder and released urine

Mice not natural hosts, therefore have no natural acquired immunity

By manioulation, models have shown a Th1 protective response (IFN_gamma) and Th2 egg induced granuloma

Mouse studies show preaziquantel is an immune reaction against worm tegument antigens

Studies in Africa and Brazil. Age profiles show most intense infection around age 10. Decreases with age. 

Gambia Study

When water contact taken into account, resistance was associated with high IgE. IgE is regulated by Il-4, a Th2 cytokine.

Uganda

Fishing community, therefore adults are exposed to water as much as children. Study carried out in Butiaba.

Blood sample taken. Treated with Praziquantel. Blood sample taken.

Removes schistosomes

Causes blebbing of the tegument. 

Immune response still needed to clear worms

boosts IgG and IgE response to worm antigens - however no effect on eggs. (boosts response to rsm22.6)

Age profiles: IgG1-Teg boosts all ages, IgE-Teg boosts older ages

Adult worm antigens important in resistance

causes immune reaction against worm tegument antigens

IgE recognises 22.6 kDa.

no significant homology with previous non-schistosome proteins

not in early post-penetration skin stages, in tegument from lung stage to adult.

Immunogold staining and electron microscopy

Rabbit anti-22kDa serum + anti-rabbit gold labbeled Ig.

Schistosome tegumental dynein light chains

 dynein is an enzyme complex involved in the microtuble based motility

dynein light chain family of tegumental associated antiens may be involved in maintaining schistosome teguments essential for survival in the blood stream

S mansoni

predominant IgE antigen in S mansoni worm. Anti-sm22.6 IgE correlates with reinfection immunity

sj22.6 redominant IgE antigen in S japonicum infections. IgE epitopes similar to codfish and beta-lactoglobulin allergens

boost in the Th2 cytokines with worm antigens, no boost with egg antigens

significant increase in IL-5 and IL-13 after treatment (especially in older ages)

Immunity in humans

Strong Th2 response in adult --> protection

IgE anti sm22.6 tegumental response => resistance

Fluctation in T1 or T2 cytokine responses following schistosome infection in mice. secretion of IFN gamma and IL-4.

T2 is associated with parasite and production of eggs. in the chronic stage, there is an increase in the T1 response leading to a T0 response

eggs stimulate the T2 cytokines as if you inject naiive mice with eggs, they produe a T2 response

Egg causes the pathophysiology in mice. they stimulate the T2 cytokine response.

Vaaccines based on restoring t1 induction, recombinant IL-12 and eggs. leads to decreased tissue fibrosis and decreased granulomas

IL-10 mediaded apoptosis of liver cells and spleen seen in acute schistosomiasis. IL-4 KO mice causes severe pathology - therefore T2 is potentially non-pathological

double IL-4 and IL-13 KO mice, no granuloma response, hepatointestinal pathology and high mortality. In CD4+T depleted mice, the T1 response is domimant. leads to fatal hepatointestinal pathology