Leishmania and Leishmaniasis pp 13-27 | Cite as
Immunology of Leishmania
Abstract
In view of existing knowledge, lymphocytes, macrophages (MΦ) and antibody co-operation the major components of the immune system are necessary for protection against the leishmania infection. The death of the parasite occurs either by stimulation of the sensitized lymphocytes through antigen load or by activating macrophages. Active VL disease is characterized by the marked elevation of humoral immune response i.e. by the production of plenty of specific as well as non-specific antibodies (Ghose et al. 1980; Ghosh et al. 1995). Antibody titers, primarily IgG rise sharply during VL, but the antibodies so generated, are apparently not protective (Bryceson and Turk 1971; Bray and Lainson 1966; Evans et al. 1990). The enormous increase in serum immunoglobulin levels in active VL is due to polyclonal activation of immunoglobulin producing cells leading to increase biosynthesis of IgG and to a lesser extent of IgM. Most of the antibodies produced during infection are not parasite specific (Clinton et al. 1969; Bunn-Moreno et al. 1985; Evans et al. 1990), but the hyper-gammaglobulinemia may have diagnostic value, IgG may reach 50 g/l and comprise 50 % of total serum proteins (Stauber 1963).
Keywords
Visceral Leishmaniasis Cutaneous Leishmaniasis Parasite Burden Parasite Growth Leishmania SpeciesReferences
- Alexander J, Bryson K (2005) T helper (h)1/Th2 and Leishmania: paradox rather than paradigm. Immunol Lett 99:17–23PubMedCrossRefGoogle Scholar
- Bogitsh BJ, Middleton OL, Ribeiro-Rodrigues R (1999) Effects of the antitubulin drug trifluralin on the proliferation and metacyclogenesis of Trypanosoma cruzi epimastigotes. Parasitol Res 85:475–480PubMedCrossRefGoogle Scholar
- Bray RS, Lainson R (1966) The immunology and serology of leishmanisis. IV. Results of Ouchterlony double diffusion tests. Trans R Soc Trop Med Hyg 60:605–609PubMedCrossRefGoogle Scholar
- Bryceson AD, Turk JL (1971) The effect of prolonged treatment with antilymphocyte serum on the course of infections with BCG and Leishmania enriettii in the guinea-pig. J Pathol 104:153–165PubMedCrossRefGoogle Scholar
- Bunn-Moreno MM, Madeira ED, Miller K, Menezes JA, Campos-Neto A (1985) Hypergammaglobulinaemia in Leishmania donovani infected hamsters: possible association with a polyclonal activator of B cells and with suppression of T cell function. Clin Exp Immunol 59:427–434PubMedGoogle Scholar
- Clinton BA, Stauber LA, Palczuk NC (1969) Leishmania donovani: antibody response to chicken ovalbumin by infected golden hamsters. Exp Parasitol 25:171–180PubMedCrossRefGoogle Scholar
- Dasgupta B, Roychoudhury K, Ganguly S, Kumar Sinha P, Vimal S, Das P, Roy S (2003) Antileishmanial drugs cause up-regulation of IFN-γ receptor 1, not only in the monocytes of visceral leishmaniasis cases but also in cultured THP1 cells. Ann Trop Med Parasitol 97:245–257PubMedCrossRefGoogle Scholar
- Evans TG, Smith D, Pearson RD (1990) Humoral factors and nonspecific immune suppression in Syrian hamsters infected with Leishmania donovani. J Parasitol 76:212–217PubMedCrossRefGoogle Scholar
- Ghalib HW, Piuvezam MR, Skeiky YA, Siddig M, Hashim FA, el-Hassan AM, Russo DM, Reed SG (1993) Interleukin 10 production correlates with pathology in human Leishmania donovani infections. J Clin Invest 92:324–329PubMedCrossRefGoogle Scholar
- Ghose AC, Haldar JP, Pal SC, Mishra BP, Mishra KK (1980) Serological investigations on Indian kala-azar. Clin Exp Immunol 40:318–326PubMedGoogle Scholar
- Ghosh MK, Nandy A, Addy M, Maitra TK, Ghose AC (1995) Subpopulations of T lymphocytes in the peripheral blood, dermal lesions and lymph nodes of post kala-azar dermal leishmaniasis patients. Scand J Immunol 41:11–17PubMedCrossRefGoogle Scholar
- Gomes RF, Macedo AM, Pena SD, Melo MN (1995) Leishmania (Viannia) braziliensis: genetic relationships between strains isolated from different areas of Brazil as revealed by DNA fingerprinting and RAPD. Exp Parasitol 80:681–687PubMedCrossRefGoogle Scholar
- Goto H, Lindoso JA (2004) Immunity and immunosuppression in experimental visceral leishmaniasis. Braz J Med Biol Res 37:615–623PubMedCrossRefGoogle Scholar
- Handman E (1997) Leishmania vaccines: old and new. Parasitol Today 13:236–238PubMedCrossRefGoogle Scholar
- Heinzel FP, Sadick MD, Mutha SS, Locksley RM (1991) Production of interferon gamma, interleukin 2, interleukin 4, and interleukin 10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc Natl Acad Sci USA 88:7011–7015PubMedCrossRefGoogle Scholar
- Holaday BJ, Sadick MD, Wang ZE, Reiner SL, Heinzel FP, Parslow TG, Locksley RM (1991) Reconstitution of Leishmania immunity in severe combined immunodeficient mice using Th1- and Th2-like cell lines. J Immunol 147:1653–1658PubMedGoogle Scholar
- Howard JG, Liew FY, Hale C, Nicklin S (1984) Prophylactic immunization against experimental leishmaniasis. II. Further characterization of the protective immunity against fatal Leishmania tropica infection induced by irradiated promastigotes. J Immunol 132:450–455PubMedGoogle Scholar
- Karp CL, el-Safi SH, Wynn TA, Satti MM, Kordofani AM, Hashim FA, Hag-Ali M, Neva FA, Nutman TB, Sacks DL (1993) In vivo cytokine profiles in patients with kala-azar. Marked elevation of both interleukin-10 and interferon-gamma. J Clin Invest 91:1644–1648PubMedCrossRefGoogle Scholar
- Kaye PM, Svensson M, Ato M, Maroof A, Polley R, Stager S, Zubairi S, Engwerda CR (2004) The immunopathology of experimental visceral leishmaniasis. Immunol Rev 201:239–253PubMedCrossRefGoogle Scholar
- Kemp M, Kurtzhals JA, Bendtzen K, Poulsen LK, Hansen MB, Koech DK, Kharazmi A, Theander TG (1993) Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis. Infect Immun 61:1069–1073PubMedGoogle Scholar
- Lehn M, Kandil O, Arena C, Rein MS, Remold HG (1992) Interleukin-4 fails to inhibit interferon-gamma-induced activation of human colostral macrophages. Cell Immunol 141:233–242PubMedCrossRefGoogle Scholar
- Leifso K, Cohen-Freue G, Dogra N, Murray A, McMaster WR (2007) Genomic and proteomic expression analysis of Leishmania promastigote and amastigote life stages: the Leishmania genome is constitutively expressed. Mol Biochem Parasitol 152:35–46PubMedCrossRefGoogle Scholar
- Locksley RM, Louis JA (1992) Immunology of leishmaniasis. Curr Opin Immunol 4:413–418PubMedCrossRefGoogle Scholar
- Manson-Bahr PE (1971) Leishmaniasis. Int Rev Trop Med 4:123–140PubMedGoogle Scholar
- Medzihradszky KF, Campbell JM, Baldwin MA, Falick AM, Juhasz P, Vestal ML, Burlingame AL (2000) The characteristics of peptide collision-induced dissociation using a high-performance MALDI-TOF/TOF tandem mass spectrometer. Anal Chem 72:552–558PubMedCrossRefGoogle Scholar
- Melby PC, Chandrasekar B, Zhao W, Coe JE (2001) The hamster as a model of human visceral leishmaniasis: progressive disease and impaired generation of nitric oxide in the face of a prominent Th1-like cytokine response. J Immunol 166:1912–1920PubMedGoogle Scholar
- Modabber F (1995) Vaccines against leishmaniasis. Ann Trop Med Parasitol 89(Suppl 1):83–88PubMedGoogle Scholar
- Murray HW (1982) Cell-mediated immune response in experimental visceral leishmaniasis. II. Oxygen-dependent killing of intracellular Leishmania donovani amastigotes. J Immunol 129:351–357PubMedGoogle Scholar
- Murray HW, Rubin BY, Rothermel CD (1983) Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. J Clin Invest 72:1506–1510PubMedCrossRefGoogle Scholar
- Murray HW, Berman JD, Davies CR, Saravia NG (2005) Advances in leishmaniasis. Lancet 366:1561–1577PubMedCrossRefGoogle Scholar
- Passos S, Carvalho LP, Orge G, Jeronimo SM, Bezerra G, Soto M, Alonso C, Carvalho EM (2005) Recombinant leishmania antigens for serodiagnosis of visceral leishmaniasis. Clin Diagn Lab Immunol 12:1164–1167PubMedGoogle Scholar
- Reiner SL, Locksley RM (1995) The regulation of immunity to Leishmania major. Annu Rev Immunol 13:151–177PubMedCrossRefGoogle Scholar
- Rezai HR, Ardehali SM, Amirhakimi G, Kharazmi A (1978) Immunological features of kala-azar. Am J Trop Med Hyg 27:1079–1083PubMedGoogle Scholar
- Sacks DL, Lal SL, Shrivastava SN, Blackwell J, Neva FA (1987) An analysis of T cell responsiveness in Indian kala-azar. J Immunol 138:908–913PubMedGoogle Scholar
- Saha S, Mondal S, Banerjee A, Ghose J, Bhowmick S, Ali N (2006) Immune responses in kala-azar. Indian J Med Res 123:245–266PubMedGoogle Scholar
- Santos WR, de Lima VM, de Souza EP, Bernardo RR, Palatnik M, Palatnik de Sousa CB (2002) Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis. Vaccine 21:30–43PubMedCrossRefGoogle Scholar
- Scott P (2003) Development and regulation of cell-mediated immunity in experimental leishmaniasis. Immunol Res 27:489–498PubMedCrossRefGoogle Scholar
- Scott DA, Coombs GH, Sanderson BE (1987) Effects of methotrexate and other antifolates on the growth and dihydrofolate reductase activity of Leishmania promastigotes. Biochem Pharmacol 36:2043–2045PubMedCrossRefGoogle Scholar
- Soto M, Requena JM, Quijada L, Perez MJ, Nieto CG, Guzman F, Patarroyo ME, Alonso C (1999) Antigenicity of the Leishmania infantum histones H2B and H4 during canine viscerocutaneous leishmaniasis. Clin Exp Immunol 115:342–349PubMedCrossRefGoogle Scholar
- Stauber LA (1963) Immunity to leishmania. Ann NY Acad Sci 113:409–417PubMedCrossRefGoogle Scholar
- Sternberg J, Turner CM, Wells JM, Ranford-Cartwright LC, Le Page RW, Tait A (1989) Gene exchange in African trypanosomes: frequency and allelic segregation. Mol Biochem Parasitol 34:269–279PubMedCrossRefGoogle Scholar
- Stobie L, Gurunathan S, Prussin C, Sacks DL, Glaichenhaus N, Wu CY, Seder RA (2000) The role of antigen and IL-12 in sustaining Th1 memory cells in vivo: IL-12 is required to maintain memory/effector Th1 cells sufficient to mediate protection to an infectious parasite challenge. Proc Natl Acad Sci USA 97:8427–8432PubMedCrossRefGoogle Scholar
- Suffia I, Ferrua B, Stien X, Mograbi B, Marty P, Rousseau D, Fragaki K, Kubar J (2000) A novel Leishmania infantum recombinant antigen which elicits interleukin 10 production by peripheral blood mononuclear cells of patients with visceral leishmaniasis. Infect Immun 68:630–636PubMedCrossRefGoogle Scholar
- Waitumbi JN, Murphy NB (1993) Inter- and intra-species differentiation of trypanosomes by genomic fingerprinting with arbitrary primers. Mol Biochem Parasitol 58:181–185PubMedCrossRefGoogle Scholar