The principal objective of this study is the identification and characterization of the major genetic effects that determine the resistance level of mice to the intestinal nematode T. spiralis. Pursuant to this goal we would further develop our analysis of three major components of host resistance; namely the rapid expulsion (RE) of ingested larvae, the rejection of adult worms in the primary infection (Adult lo) and resistance to migratory newborn larvae (anti-NBL). Specifically, we wish to characterize the gene and define linkage for lhe-1, the gene governing RE in mice. We will continue our analysis of genetic control of Adult lo and define the genetic factors that influence anti-NBL immunity. Data to hand indicate that major control of each of these responses is determined by genes that are not linked to the mouse MHC. A strain analysis of responsiveness also suggests that each genetic system is independent of the other. The strength of the Adult lo response is determined by at least two non-MHC. A strain analysis of responsiveness also suggests that each genetic system is independent of the other. The strenght of the Adult lo response is determined by at least two non-MHC genes (AA and BB) which are co-dominant and additive. In this study RE, Adult lo and anti-NBL will be analyzed by single approach that comprises; l) continuing strain survey to phenotypicaly characterize the response pattern of a wide variety of inbred strains, including recently derived wild mouse strains. The objective is to define the phenotypic variation that exists in mice and identify the strongest and weakest responder for further genetic analysis; 2) analysis of selected F1 hybrids to characterize dominance, complementation and autosomal or sex-linked character, followed by a segregation analysis of F2 and backcross to estimate the numbers of loci involved; 3) linkage analysis of major genes; for Adult lo (AA and BB) we will also use recombinant inbred mouse lines; 4) definition of chromosomal position. We will use the following approach to examine function for the AA and BB genes. Antibody responses to adult worm excretion/secretion antigens will be analyzed to determine antibody kinetics, repertoire and class-specificity. Secondly, we will determine whether AA and BB operate through bone-marrow derived cells by using radiation chimeras. Thirdly, we will measure strain-specific delayed hypersensitivity responses to adult antigens. These studies will define the function of the genes that we identify, particulary as it relates to their role in acquired resistance to infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016740-06
Application #
3126812
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1981-04-01
Project End
1990-03-31
Budget Start
1989-01-01
Budget End
1990-03-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Bell, R G (1992) Trichinella spiralis: evidence that mice do not express rapid expulsion. Exp Parasitol 74:417-30
Zhu, D Z; Bell, R G (1990) Trichinella spiralis: murine strain variation in response to monoclonally defined, protective, nonstage-specific antigens. Exp Parasitol 70:330-43
Zhu, D Z; Bell, R G (1990) Genetic analysis of the relationship between interleukin production and worm rejection in Trichinella spiralis-infected inbred mice. J Parasitol 76:703-10
Zhu, D Z; Lu, X F; Bell, R G (1990) Antigen-specific lymphocyte proliferative responses in inbred mice after Trichinella spiralis infection. J Parasitol 76:85-92
Zhu, D H; Bell, R G (1989) IL-2 production, IL-2 receptor expression, and IL-2 responsiveness of spleen and mesenteric lymph node cells from inbred mice infected with Trichinella spiralis. J Immunol 142:3262-7
Bell, R G (1988) Genetic analysis of expulsion of adult Trichinella spiralis in NFS, C3H/He, and B10.BR mice. Exp Parasitol 66:57-65
Bell, R G; Liu, W M (1988) Trichinella spiralis: quantitative relationships between intestinal worm burden, worm rejection, and the measurement of intestinal immunity in inbred mice. Exp Parasitol 66:44-56
Bell, R G; Wang, C H (1987) The Trichinella spiralis newborn larvae: production, migration and immunity in vivo. Wiad Parazytol 33:453-78
Wang, C H; Bell, R G (1986) Trichinella spiralis: newborn larval migration route in rats reexamined. Exp Parasitol 61:76-85
Bell, R G; Wang, C H; Ogden, R W (1985) Trichinella spiralis: nonspecific resistance and immunity to newborn larvae in inbred mice. Exp Parasitol 60:101-10

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