Immunomodulation of Schistosomiasis

1. UNIVERSITY OF BUEA
FACULTY OF SCIENCE
DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR
BIOLOGY
“PROTECTIVE IMMUNE RESPONSES AND IMMUNOPATHOLOGY OF
SCHISTOSOMIASIS’’
PRESENTED BY:
TESSY KOKO(SC18P224)
&
TANYI PRIDE BOBGA(SC18P277)
LECTURERS:
Prof P.K TITANJI
Prof ACHIDI ERIC A MARCH, 2019
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2. OUTLINE OF PRESENTATION
INTRODUCTION
LIFE CYCLE
ORIGIN OF IMMUNOPATHOLOGY
IMMUNOPATHOLOGY OF SCHISTOSOMIASIS
CONTROL OF IMMUNOPATHOLOGY
SPECTRUM OF CLINICAL DISEASE
 PROTECTIVE MECHANISMS
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3. INTRODUCTION
 Causes Schistosomiasis and of genus Schistosoma
Over 19 species of Schistosoma wide range of host- range and accounts for
its public health relevance with varied clinical disease.
93 countries at risk, 600mil vulnerable & 200mil I(Tchente et al.,2013)
 S.haematobium most virulent( 112mil Vulnerable, 80mil I, 15000deaths)
Cameroon over 5million at risk, 2million AI (Mewabo et al.,2017)
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4. 4

5. ORIGIN OF IMMUNOPATHOLOGY
Large due to eggs lodging which →vigorous collagen-rich granulomatous
response→servere hepatitic fibrosis
 T-cell deficient mice mice(CD4+ Th fail to mount effective granulomatous
response.[Pesce et al.,2006]
Wt striking drift from Th1→Th2-dominated response(Th2 cytokines prin
pathology)
 Inducing mice with 1L-12 ameliorates hepatosplenic pathology.
 Th2 role expt: mice deficient 1L-4/STAT6 deficient → devt of granulo
resp→fibrosis[Mark et al.,2007]
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6. IMMUNOPATHOLOGY OF SCHISTOSOMIASIS
 The Clin Manifestations progress acute→sub-acute and Chronic stages
Succession to innate, TH1 &TH2 adaptive stages & concomitant immunity
Sequelae may occur [Rashad.,2013]
Subacute:parasite maturity and formation of granulomata around egg
Chronic morbidity assoc to healing of granulomata by fibrosis & Calcification
, deposits of S. Ag-Ab complexe in renal glomeruli [Mark et al.,2007]
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7. CONTROL OF IMMUNOPATHOLOGY
Th1 & Th2 →recalibration of the immune homeostasis
 Treg(CD4+ Tcells control activation of autorective cells
Forkhead box protein 3(Foxp3) +nat Treg(Reinman.,2006).
Inducible Treg mimic proliferation of Ag-driven effector T reponses.
Schistosomiasis both Nat & Inducible →suppression +orchestration
Lyso-PS→1L-10→TLR-2→signaling DC(Rutitzky et al.,2005)
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8. SPECTRUM OF IMMUNOPATHOLOGY TO SCHISTOSOMIASIS
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9. Immunomodulation of
Schistosomiasis (1/2)
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10. Immunomodulation of Schistosomiasis (2/2)
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11. Protective Immune responses (1/4)
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12. 1. Delayed concomitant immunity
• Host infected with schistosome resists reinfection with fresh
cercariae and at the same time maintains adult schistosome.
• The parasite of the already existing infection are not cleared by
this immunity. Here the later stage of the parasite causes an
immune response to new cercariae.
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13. 2. Praziquantel treatment: passive
vaccination
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14. 3.Granuloma formation
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15. 4. Vaccines
• Bilhvax is in an advanced stage of clinical development for S. haematobium
infection and targets the parasite’s glutathione-s- transferase.
• With few Schistosoma vaccine candidates in clinical trials, unexplored antigens
from the vulnerable schistosomulum are being considered as possible vaccine
candidates.
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16. Conclusion
Schistosomes are complex multicellular organisms, and this may partly explain
why current vaccines composed of a single antigen are not capable of inducing
long-lived protective immunity.
Multiple-antigen preparations to target different aspects and stages of the
parasite have been proposed for vaccine development.
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17. References
• Hotez P.J., and Diemert D.D., (2019). Advancing the development of a human schistosomiasis vaccine. Trends in Parasitology.
35(2): 104-108
• Colley, D.G. and Secor, W.E., (2013). Immunology of Human Schistosomiasis. Parasite Immunology. DOI: 10.1111/pim.12087.
• Liu F., Lu J., Hu W., et al., (2006). New perspectives on host-parasite interplay by comparative
• transcriptomic and proteomic analyses of Schistosoma japonicum. PLoS Pathog. 2: e29.
• Hokke C.H., Fitzpatrick J.M., & Hoffman K.F., (2007). Integrating transcriptome, proteome and glycome analyses of Schistosoma
biology. Trends in Parasitology. 23: 165—174.
• Fu C.L., Odegaard J.I., Herbert D.R. & Hsieh M.H., (2012) A novel mouse model of Schistosoma haematobium egg-induced
immunopathology. PLoS Pathology. 8: e1002605
• Caldas I.R., Campi-Azevedo A.C., Oliveira L.F., Silveira A.M., Oliveira R.C. & Gazzinelli G., (2008). Human schistosomiasis
mansoni: immune responses during acute and chronic phases of the infection. Acta Trop. 108: 109—117.
• Woolhouse M.E., & Hagan P., (1999). Seeking the ghost of worms past. Nat. Med. 5, 1225–1227
• Mutapi, F., Ndhlovu, P.D., Hagan, P., Spicer, J.T., Mduluza, T., Turner, C.M., Chandiwana, S.K., Woolhouse, M.E., (1998).
Chemotherapy accelerates the development of acquired immune responses to Schistosoma haematobium infection. Journal of
Infectious Diseases. 178, 289–293.
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18. THANKS FOR YOUR KIND ATTENTION
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