Home » Volumes » Volume 25 April/June 1992 » Human immune responses during schistosomiasis mansoni

Human immune responses during schistosomiasis mansoni

Giovanni Gazzinelli; Daniel G. Colley

DOI: 10.1590/S0037-86821992000200006


Studies of immune responses as they occur in patients with schistosomiasis appear to progress relative to corrent technological advances, and to advance despite the understandable inability to pursue in vivo manipulations in this host/parasite system. Emphasis is most often placed on making immunological comparisons between such patient groups as reinfected/non-reinfected, intestinals/hepatosplenic, high/low intensities of infection, infected/uninfected within endemic areas, and those born of infected/uninfected mothers. Based on these types of comparisons, reasonable conjectures can be made regarding the immunological occurrences during this chronic exposure condition. Some consideration is now being given to the immune mechanisms of some of the observations made, and while some of these must then be carried back to experimental models for further manipulation-based analysis, new technological developments continue to assist in the field/bench ability to ask questions that might assist our understanding to a point where this knowledge can be applied to shaping developmental approaches to vaccine development and the goal of alleviating morbidity.

Keywords: Schistosomiasis. Immune responses. Immunoregulation.


O estudo da resposta imune de pacientes com esquistossomose progride em função do avanço tecnológico, apesar das dificuldades de manipulação in vivo deste complexo sistema parasita-hospedeiro. A ênfase nos estudos tem sido mais freqüentemente dirigida para comparações entre grupos característicos de indivíduos, tais como infectado/não infectado, reinfectado/ não reinfectado, assintomático/hepato-esplênico, com intensidade de infecção alta/baixa, etc. Baseado nessas comparações tem-se obtido informações que permitem conjecturas razoáveis com relação à regulação imunológica, susceptibilidade e resistência e até mesmo considerações sôbre mecanismos, que têm sido mais apropriadamente analisados, entretanto, em sistemas experimentais. Tais estudos têm como finalidade a compreensão das camas e eventos que le vam à morbidade e ao desenvolvimento de uma vacina humana anti- esquistosoma.

Palavras-chave: Esquistosomíase. Resposta imune. Imuno-regulação.



Full text available only in PDF format.

Texto completo disponível apenas em PDF.




1. Abdel-Salam E, Abdel-Khalih A, Abdel-Meguid A, Barakut W, Mahmond AA. Association of HLA class I antigens (Al, B5, B8 and CW2) with disease manifestations and infection inhuman schistosomiasis mansoni in Egypt. Tissue Antigens 27: 142-146, 1986.         [ Links ]

2. Abdel-Salam E, Ishaac S, Mahmoud AAF. Histocompatibility-linked susceptibility for hepatosplenomegaly in human schistosomiasis. Journal of Immunology 123: 1829-1831, 1979.         [ Links ]

3. Abel L, Demenais F, Prata A, Souza AE, Dessein A. Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni. American Journal of Human Genetics 48: 959-970, 1991.         [ Links ]

4. Alves-Brito CF, Simpson AJG, Bahia-Oliveira LMC, Rabello ALT, Rocha RS, Lambertucci JR, Gazzinelli G, KatzN, Correa-OliveiraR. Analysis of anti-KLH antibody in Brazilians supports its use for the diagnosis of acute schistosomiasis mansoni. Transactions of The Royal Society of Tropical Medicine and Hygiene 86:53-56, 1992.         [ Links ]

5. Bahia-Oliveira LMG, Gazzinelli G, Eloi-Santos SM, Cunha-Melo JR, Alves-Oliveira LF, Silveira AMS, Viana IRC, Carmo J, Souza A, Correa- Oliveira R. Differential cellular reactivity to adult worm antigens of patients with different clinical forms of schistosomiasis mansoni. Transactions of the Royal Society of Tropical Medicine and Hygiene 86:57-61, 1992.         [ Links ]

6. Barsoum IS, GamilFM, Al-KhafifMA, Ramzy RM, El Alamy MA, Colley DG. Immune responses and immunoregulation during human schistosomiasis in Egypt. I. Effect of treatment on in vitro responsiveness. The American Journal of Tropical Medicine and Hygiene 31:1181-1187, 1982.         [ Links ]

7. Boctor FN, Peter JB. lgG subclasses in human chronic schistosomiasis: over-production of scchistosome-specific and non-specific IgG4. Clinical and Experimental Immunology 82: 574- 578, 1989.         [ Links ]

8. Butterworth AE, Corbett EL, Dunne DW, Fulford AJC, Kimani G, Gachuhi RK, Klumpp R, Mbugiia G, Ouma JH, Arap Siongok RK, Sturrock RF. Immunity and morbidity in human schistosomiasis. In: McAdam KPWJ(ed) New Strategies in Parasitology. Churchill-Livingstone,London p. 193- 210, 1989.         [ Links ]

9. Capron M, Camus D, Carlier Y, Figueiredo JFM, Capron A. Immunological studies in human schistosomiasis. II. Antibodies cytotoxic for Schistosoma mansoni schistosomules. The American Journal of Tropical Medicine and Hygiene 26: 248- 253, 1977.         [ Links ]

10. Cheever AW. A quantitative post-mortem study of schistosomiasis mansoni in man. The American Journal of Tropical Medicine and Hygiene 17: 38- 64, 1968.         [ Links ]

11. Clarke VV. Evidence of the development in man of acquired resistance to infection of schistosoma spp. Central Africa Journal of Medicine 12(Suppl. I): 1- 30, 1966.         [ Links ]

12. Colley DG. Dynamics ofthe human immune response to schsistosomes. In: Mahmoud AAFfed) Bailliere’s Clinical Tropical Medicine and Communicable Diseases, Vol. 2,Schistosomiasis, Bailliere-Tindall, London 315-332, 1987.         [ Links ]

13. Colley DG, Barsoum IS, Dahawi HSS, Gamil F, Habib M, El Alamy MA. Immune responses and immunoregulation in relation to Schistosomiasis in Egypt. III. Immunity and longitudinal studies of in vitroresponsiveness after treatment. Transactions ofThe Royal Society Tropical Medicineand Hygiene 80: 952-957, 1986.         [ Links ]

14. Colley DG, CookJ R,Freeman Jr GL,Bartholomew RK, Jordan P. Immune responses during human schistosomiasis mansoni. I. In vitro lymphocyte blastogénie responses to heterogeneous antigenic preparation from schistosome eggs, worms and cercariae. International Archives of Allergy and Applied Immunology 53: 420-443, 1977.         [ Links ]

15. Colley DG, Garcia AA, Lambertucci JR, Parra JC, Katz N, Rocha RS, Gazzinelli G. Immune responses during human schistosomiasis. XII Differential responsiveness in patients with hepatosplenic disease.The American Journal of Tropical Medicine and Hygiene 35:793-802, 1986.         [ Links ]

16. Colley DG, Katz N, Rocha RS, Abrantes W, da Silva AL, Gazzinelli G. Immune responses during human schistosomiasis mansoni. IX. T lymphocyte subset analysis by monoclonal antibodies in hepatosplenic disease. Scandinavian Journal of Immunology 17: 297-301, 1983.         [ Links ]

17. Colley DG, Montesano MA, Powell MR, Eloi- Santos SM, Parra JC, Goes AM, Doughty BL Correa-Oliveira R, Rocha RS , Gazzinelli G. Idiotype networks in schistosomiasis. In: Mc Adam KPWJ (ed) New strategies in Parasitology, Churchill- Livingstone, London p. 179-190, 1989.         [ Links ]

18. Correa-Oliveira, R, DusseLMS, VianalRC, Colley DG, Carvalho OS, Gazzinelli G. Human antibody responses against schistosomal antigens. I. Antibodies from patients with ancylostoma, Ascaris lumbricoides or Schistosoma mansoni infections react with schistosome antigens. The American Journal of Tropical Medicine and Hygiene38:348-355, 1988.         [ Links ]

19. Correa-OliveiraR, OliveiraGC, GolgherDB, Viana JRC, Colley DG, Carvalho OS, Rocha RS, Katz N, Gazzinelli G. Analysis of antibody responses of Schistosoma mansoni-infccted patients against schistosomal antigens. Memórias do Instituto Oswaldo Cruz 82 (Suppl IV): 179-181, 1987.         [ Links ]

20. Correa-OliveiraR, PearceEJ, Oliveira GC, Golgher DB, Katz N, Bahia LG, Carvalho OS, Gazzinelli G. Thehuman immune response to defined immunogens of Schistosoma mansoni: elevated antibody levels to paramyosin in stool-negative individuals from two endemic areas in Brazil. Transactions of the Royal Society of Tropical M edicine and Hygiene 83:1205- 1209, 1989.         [ Links ]

21. Dabes TMP, Garcia AA, Colley DG, Ramalho- Pinto FJ. Lymphokine production by blood or spleen mononuclear cells from patients with schistosomiasis mansoni. The American Journal of Tropical Medicineand Hygiene40:273-281,1989.         [ Links ]

22. Dessein AJ, Begley M, DemeareC, CailolD, Fueri J, Galvão dos Reis M, Andrade Z, Prata A, Bina JC. Human resistance to Schistosoma mansoni is associated with IgG reactivity to a 37-kDa larval surface antigen. Journal of Immunology 140:2727- 2736, 1988.         [ Links ]

23. Doughty BL, Goes AM, ParraJC, Rocha RS, Cone C, Colley DG, Gazzinelli G. Anti-idiotypic T cells in human schistosomiasis. Immunological Investigation 18: 373-388, 1989.         [ Links ]

24. Dunne DW, Grabowska AM, Fulford AJC, Butterworth AE, Sturrock RF, Koech D, Ouma JH. Human antibody responses to Schistosoma mansoni: the influence of epitopes shared between different lifecylcle stages on the response to the sehistosomulum. European Journal of Immunology 18: 123-131, 1988.         [ Links ]

25. Dusse LMS. Estudo da atividade citotóxica de soros de pacientes infectados com S. mansoni contra esquistossomulos in vitro. Tese de mestrado, Fundação Oswaldo Cruz, Rio de Janeiro, 1986.         [ Links ]

26. Ellner JJ, Olds GR, Osman GS, El Kholy A, Mahmoud AAF. Dichotomies in the reactivity to worm antigen in human schistosomiasis mansoni. Journal of Immunology 126: 309-312, 1981.         [ Links ]

27. Eloi-Santos SM, Novato-Silva E, Maseli VM, GazzinelliG, Colley DG, Correa-Oliveira R. Idiotype sensitization in utero of children bom to mothers with schistosomiasis or Chagas’ disease. Journal of Clinical Investigation 84: 1028-1031, 1989.         [ Links ]

28. Everngard B, Hammarstrom L, Smith CIE, Johansson SGO, Linder E. Subclass distribution and IgE responses after treatment in human schistosomiasis. Clinical and Experimental Immunology 73: 383-388, 1988.         [ Links ]

29. FeldmeierH, Gastl GA, PoggenseeU, Kortmann C, Daffalla AA, Peter HH. Relationship between intensity of infection and immunomodulation in human schistosomiasis. I. Lymphocyte subpopulations and specific antibody responses. Clinical and Experimental Immunology 60: 225- 223, 1985.         [ Links ]

30. Galvão-Castro B, Bina JC, Prata A, Lambert PH. Correlation of circulating immune complexes and complement breakdown products with the severity of the disease in human schistosomiasis. The American Journal of Tropical Medicineand Hygiene 30: 1238-1246, 1981.         [ Links ]

31. Gastl GA, Feldmeier H, Doehing E, Kortmann C, Daffalla AA, Peter HH. Numerical and functional alterationsof lymphocytes in human schistosomiasis. Scandinavian Journal of Immunology 19: 469-479, 1984.         [ Links ]

32. Gazzinelli G, Katz N, Rocha RS, Colley DG. Immune responses during human schistosomiasis mansoni. VIII. Differential in vitro cellular responsiveness to adult worm and schistosomular tegumental preparations. The American Journal of Tropical Medicine and Hygiene 32:326-333,1983.         [ Links ]

33. Gazzinelli G, Katz N, Rocha RS, Colley DG. Immune response during schistosomiasis mansoni. X. Production and standartization of an antigen- induced mitogenic activity by peripheral blood mononuclear cells from treated but not active cans of schistosomiansis. Journal of Immunology 130: 2891-2895, 1983.         [ Links ]

34. Gazzinelli G, Lambertucci JR, Katz N, Rocha RS, Lima MS, Colley DG. Immune responses during human schistosomiasis mansoni. XI. Immunological status of patients with acute infections and after treatment. Journal of Immunology 135: 2121-2127, 1985.         [ Links ]

35. Gazzinelli G, Montesano MA, Correa-Oliveira R, Lima MS, Katz N, Rocha RS, Colley DG. Immune response in different clinical groups of schistosomiasis patients. Memórias do Instituto Oswaldo Cruz 82 (Supl IV): 95-100, 1987.         [ Links ]

36. Goes AM, Gazzinelli G, Rocha R, KatzN, Doughty BL. Granulomatous hypersensitivity to Schistosoma mansoniegg antigens in human schistosomiasis. III. In vitro granuloma modulation induced by immune complexes. The American Journal of Tropical Medicine and Hygiene 44: 434-443, 1991.         [ Links ]

37. Hafez M, Hassan SA, El-Tahan H, El-Shennawy F, Khashaba M, Al-Tonbary Y, El-Morsi Z, El-Sallab SH, EI-Desoky I, El-Shazly A, Eteba S. Immunogenetic susceptibility for post-schistosomal hepatic fibrosis. The American Journal of Tropical Medicineand Hygiene 44: 424-433, 1991.         [ Links ]

38. Hagan P, Blumenthal UJ, Dunn D, Simpson AJG, Wilkins HA. Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 349: 243-245, 1991.         [ Links ]

39. Henderson GS, Conary JT, Summar M, McCurley TL, Colley DG. In vivo molecular analysis of lymphokines involved in the murine immune response during Schistosoma mansoni infection. I. IL-4, not IL-2 mRNA, is abundant in the granulomatous livers, mesenteric lymphnodes, and spleens of infected mice. Journal of Immunology 147: 992- 997, 1991.         [ Links ]

40. Hirayama K, Matsushita S, Kikuchi I , Iuchi M, Ohta N, Sasazuki T. HLA-DQ is epistatic to HLA-DR in controlling the immune response to schistosomal antigen in humans. Nature 327: 426-430, 1987.         [ Links ]

41. Jassim A, Hassan K, Catty D. Antibody isotypes in human schistosomiasis mansoni. Parasite Immunology 9: 627-650, 1987.         [ Links ]

42. Kanamura HY, Hoshino-Shimizu S. Camargo ME, da Silva LC. Class specific antibodies and fluorescent staining patterns in acute and chronic forms of schistosomiasis mansoni. The American Journal of Tropical Medicineand Hygiene 28:242-248, 1979.         [ Links ]

43. Khafile J, Dunne DW, Richardson BA, Mazza G, Thome KJI, Capron A, Butterworth AE. Functional roleof human IgG subclasses in eosinophil-mediated killing of schistosomula of Schistosoma mansoni. Journal of Immunology 142: 4422-4427, 1989.         [ Links ]

44. King CH, El Ibiary S, El Nawawi M, Sawyer J, Griffin A, El Hawey A, Mahmoud AAF. Intensity of Schistosoma mansoni infection in a human population is inversely correlated with antibody response to SmW68, a protective parasite antigen. Journal of Infectious Disease 160: 686-691, 1989.         [ Links ]

45. Kloetzel K, da Silva JR. Schistosomiasis mansoni acquired in adulthood: behaviour of egg counts and the intradermal test. The American J oumal of Tropical Medicine and Hygiene 16: 167-169, 1967.         [ Links ]

46. Lima MS, Gazzinelli G, Rocha RS, Katz N, Colley DG. Demonstration of Leukocyte Inhibitory Factor (LIF) in human schistosomiasis mansoni and its evaluation from patients in an endemic setting. Clinical Immunology and Immunopathology 37: 351-359, 1985.         [ Links ]

47. Lunde MN, Ottesen EA, Cheever AW. Serological differences between acute and chronic schistosomiasis mansoni detected by enzyme-linked immunoabsorbant assay (ELISA). The American Journal of Tropical Medicine and Hygiene 28: 87- 91, 1979.         [ Links ]

48. Mansour MM, Omer Ali P, Farid Z, Simpson AJG, Woody JW. Serological differentiation of acute and chronic schistosomiasis mansoni by antibody responses to keyhole limpet hemocyanin. The American Journal of Tropical Medicine and Hygiene 41:338-344, 1989.         [ Links ]

49. Montesano MA, Freeman GL, Gazzinelli G, Colley DG.Recognition by monoclonal anti-idiotypic antibodies of several idiotypes on a monoclonal antisoluble schistosomal egg antigen antibody and antisoluble schistosomal egg antigen antibodies from patients with different clinical forms of infection. Journal of Immunology 145: 3095-3099, 1990.         [ Links ]

50. Montesano MA, Freeman Jr GL, Gazzinelli G, Colley DG. Expression of cross-reactive, shared idiotypes on anti-SEA antibodies from humans mice with schistosomiasis. Journal of Immunology 145: 1002-1008, 1990.         [ Links ]

51. Montesano MA, Lima MS, Correa-Oliveira R, Gazzinelli G, Colley DG, XVI. Idiotypic differences in antibody preparations from patients with different clinical forms of infection. Journal of Immunology 142: 2501-2506, 1989.         [ Links ]

52. Mosmann TR, Coffman RL. Thl and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 7: 145-173, 1989.         [ Links ]

53. Nash TE, Cheever AW, Ottesen EA, Cook JA. Schistosome infection in humans: perspectives and recent findings. Annals of Internal Medicine 97: 740-754, 1982.         [ Links ]

54. Nash TE, Garcia-Coyco C, Ruiz-Tiben E, Nazario- Lopez HA, Vazquez G, Torres-Borges A. Differentiation of acute and chronic schistosomiasis by antibody responses to specific schistosome antigens. The American Journal Tropical Medicine and Hygiene 32: 776-784, 1983.         [ Links ]

55. Ohta N, Nishimura YK, Iuchi M, Sasazuki T. Immunogenetic analysis of patients with post schistosomal liver fibrosis in man. Clinical and Experimental Immunology 49: 493-499, 1982.         [ Links ]

56. OmerAliP, MansourM, Woody LN, SmithersSR, Simpson AJG. Antibody to carbohydrate and polypeptide epitopes on the surfaceof schistosomula of Schistosoma mansoni in Egyptian patients with acute and chronic schistosomiasis. Parasitology 98: 417-424, 1989.         [ Links ]

57. Ottesen EA. Modulation of the host response in human schistosomiasis. I. Adherent supressor cells that inhibit lymphocyte proliferation responses to parasite antigens. Journal of Immunology 123: 1639-1644, 1979.         [ Links ]

58. Ottesen EA, Hiatt RA, Cheever AW, Sotomayor ZR, Neva FA. The acquisition and loss of antigen- specific cellular immune responsiveness in acute and chronic schistosomiasis in man. Clinical and Experimental Immunology 33: 38-47, 1978.         [ Links ]

59. Parra JC, LimaM, Colley TA, GazzinelliG, Colley DG. Flow cytometric analysis of schistosomal patient’s lymphoblasts stimulated in vitro leg soluble antigens (SEA), anti-SEA idiotypes and staphylococcal enterotoxin B (SEB). In: Abstracts of International Symposium on Schistosomiasis. Recife p. 20-25, 1991.

60. Parra JC, Lima MS, Gazzinelli G, Colley DG. Anti- idiotypic T cells can recognize and respond to anti- SEA idiotypes directly. Journal of Immunology 140: 2401-2405, 1988.         [ Links ]

61. Pearce EJ, Caspar P, Grzych JM, Lewis FA, Sher A. Down regulation of Thl cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. Journal of Experimental Medicine 173: 159-166, 1991.         [ Links ]

62. Rocklin RE, Brown AP, Warren KS, Pelley RP, Houba V, Siongok TKA, Ouma J, Sturrock RF, Butterworth AE. Factors that modify the cellular- immune response in patients infected by Schistosoma mansoni. Journal of Immunology 125: 1916-1923, 1980.         [ Links ]

63. Sasazuki T, Ohta N, Kaneoka R, Kojima S. Association between an HLA paplotype and low responsiveness to schistosomal worm antigen in man. Journal of Experimental Medicine 152: 3145- 3185, 1980.         [ Links ]

64. Simpson AJG, Yi X, Lilliwhitte J, Omer Ali P, Kelly C, Mott R, Smithers SR, Correa-Oliveira R, Katz N, Rumjanek F, Hagan P. Dissociation of antibody responses during human schistosomiasis and evidence for enhancement of granuloma size by anti-carbohydrate IgM. Transactions of the Royal Society of Tropical Medicine and Hygiene 84:808- 814,1990         [ Links ]

65. Tweardy DJ, Osman GS, El Kholy A, Ellner JJ. Failure of immuno suppressive mechanisms in human Schistosoma mansoni infection with hepatosplenomegaly. Journal of Clinical Microbiology 25: 768-773, 1987.         [ Links ]

66. Wilson CS, Ellner JJ, Dinarello CA, Keusch GT, El Kholey A. Dissociation of immunoregulatory function of blood monocytes from maturational state and expression of interleukin-1 in humans chronically infected with Schistosoma mansoni. The American Journal of Tropical Medicine and Hygiene 42: 234-242, 1990.         [ Links ]

67. Zwingenberger K, Irschich E, Siqueira-Vergetti JG, Correia-Dacal R, Janssen-Rosseck R, Benzie U, Huber C, Feldmeier H. Release of interleukin 2 and gama interferon by peripheral blood mononuclear cells in human Schistosoma mansoni infection normalizes after chemotherapy. Scandinavian Journal of Immunology 30: 463-471, 1989.         [ Links ]



Recebido para publicação em 18/12/91.



Centro de Pesquisas René Rachou (FIOCRUZ), Belo Horizonte, MG, Brazil, and the Veterans Affair Medical Center and Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37212.
Support from National Institutes of Health, UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, Conselho Nacional de Desenvolvimento Cientifico e Tecnológico do Brasil, e Fundação de Amparo’a Pesquisa de Minas Gerais (Brasil).