OF WORK: PURPOSE: Nine years ago, I proposed a new model of the immune system (the Danger model) based on the assumption that the immune system's function is to discriminate between dangerous and harmless things rather than self and non-self. Because this model has tremendous implications for such subjects as cancer, transplantation, neonatal and adult vaccines, parasitology, and autoimmunity, we have been testing its basic premises and its applicability in several areas. RESULTS FROM THE PAST YEAR: 1) NEONATAL IMMUNITY: neonatal mice respond to a vaccine, even if they have received passive antibody from their mothers. Thus, at least in mice, there does not seem to be any inhibitory effect of maternal antibody. 2) TOLERANCE (in HEMOPHILIA) : A) oral administration of Factor VIII or factor IX induces immunological tolerance and corrects the bleeding time in hemophilic mice. 3) T CELLS: A) naive and memory T cells do not need MHC molecules for survival or the initiation of homeostatic division, but do seem to need MHC for the transition to CD44-high memory cells B) CD4 helper T cells can reject tumors in the absence of CD8 killers 4) DENDRITIC CELLS: A) dendritic cells can be conditioned by fed T cells to induce IL-4 production from naive T cells B) the early IL-4 necessary to generate Th2 responses seems to have its effect on dendritic cells. C) Memory T cells communicate with naive T cells via a dendritic cell, by educating the dendritic cell to pass on the appropriate messages. D) dendritic cells do not make IL-12p70 upon LPS stimulation unless they are also allowed to interact with an activated T cell.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000581-16
Application #
6985874
Study Section
Lung Cellular, Molecular, and Immunobiology Study Section (LCMI)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Kamala, Tirumalai; Nanda, Navreet K (2009) Protective response to Leishmania major in BALB/c mice requires antigen processing in the absence of DM. J Immunol 182:4882-90
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Usharauli, David; Kamala, Tirumalai (2008) Brief antigenic stimulation generates effector CD8 T cells with low cytotoxic activity and high IL-2 production. J Immunol 180:4507-13
Chan, William F N; Perez-Diez, Ainhoa; Razavy, Haide et al. (2007) The ability of natural tolerance to be applied to allogeneic tissue: determinants and limits. Biol Direct 2:10
Perez-Diez, Ainhoa; Joncker, Nathalie T; Choi, Kyungho et al. (2007) CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood 109:5346-54
Perez-Diez, Ainhoa; Morgun, Andrey; Shulzhenko, Natalia (2007) Microarrays for cancer diagnosis and classification. Adv Exp Med Biol 593:74-85
Matzinger, Polly (2007) Friendly and dangerous signals: is the tissue in control? Nat Immunol 8:11-3

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