Abstract

The research project proposed herein examines the immune mechanisms resulting in an asymptomatic, hyporesponsive state among microfilaremic individuals (MF) with Iymphatic filariasis. It is hypothesized that MF subjects develop an Ag-specific tolerance in which antigen presenting cells (APC) generate co-stimulatory signals that promote a Th2.like pattern of cytokines which are: i) anti-inflammatory-,ii) produce counter regulatory cytokines (e.g.,IL.10, TGFbeta) that actively modulate Th1 responses, and iii) favor generation of immediate hypersensitivity responses (e.g. IgE and eosinophilia) that promote concomitant immunity. In addition, this proposal seeks to establish wbether the duration and intensity of exposure to infective larvae and worm burdens are the major factors which determine Th2 dominance among MF subjects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Modified Research Career Development Award (K04)
Project #
5K04AI001202-05
Application #
2671347
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1994-09-01
Project End
1999-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Stavitsky, Abram B (2004) Regulation of granulomatous inflammation in experimental models of schistosomiasis. Infect Immun 72:1-12
Stavitsky, Abram B; Xianli, Jia (2002) In vitro and in vivo regulation by macrophage migration inhibitory factor (MIF) of expression of MHC-II, costimulatory, adhesion, receptor, and cytokine molecules. Cell Immunol 217:95-104
King, C L; Connelly, M; Alpers, M P et al. (2001) Transmission intensity determines lymphocyte responsiveness and cytokine bias in human lymphatic filariasis. J Immunol 166:7427-36
Farah, I O; Kariuki, T M; King, C L et al. (2001) An overview of animal models in experimental schistosomiasis and refinements in the use of non-human primates. Lab Anim 35:205-12
King, C L; Xianli, J; Stavitsky, A B (2001) Murine schistosomiasis mansoni: coordinate cytokine regulation and differences in cellular immune responses of granuloma cells and splenocytes to endogenous and exogenous schistosome egg antigens. Parasite Immunol 23:607-15
Tobian, A A; Mehlotra, R K; Malhotra, I et al. (2000) Frequent umbilical cord-blood and maternal-blood infections with Plasmodium falciparum, P. malariae, and P. ovale in Kenya. J Infect Dis 182:558-63
Farah, I O; Mola, P W; Kariuki, T M et al. (2000) Repeated exposure induces periportal fibrosis in Schistosoma mansoni-infected baboons: role of TGF-beta and IL-4. J Immunol 164:5337-43
Farah, I O; Nyindo, M; King, C L et al. (2000) Hepatic granulomatous response to Schistosoma mansoni eggs in BALB/c mice and olive baboons (Papio cynocephalus anubis). J Comp Pathol 123:14-Jul
Martin, D L; King, C L; Pearlman, E et al. (2000) IFN-gamma is necessary but not sufficient for anti-CD40 antibody-mediated inhibition of the Th2 response to Schistosoma mansoni eggs. J Immunol 164:779-85
Nyindo, M; Kariuki, T M; Mola, P W et al. (1999) Role of adult worm antigen-specific immunoglobulin E in acquired immunity to Schistosoma mansoni infection in baboons. Infect Immun 67:636-42

Showing the most recent 10 out of 17 publications