SUMMARY 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 do not seem to be impaired in their ability to respond to a vaccine, even if they have received passive antibody from their mothers 2) TOLERANCE (in HEMOPHILIA) : A) oral administration of Factor VIII or factor IX induces immunological tolerance and corrects the bleeding time in hemophiliac 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 activated by endogenous hydrophobic substances 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.