Alcohol has a suppressive effect on both the cellular immune response and humoral immune response. Animals and humans who have ingested alcohol have a decrease in antibody response to new antigens. The mechanisms by which alcohol suppresses antibody formation are not known. The principal investigator will use an in vitro model of antibody formation to test the hypothesis that alcohol inhibits the antibody response by interfering with biochemical pathways responsible for initiating and sustaining the immune response in B and T lymphocytes. She will use the unique long term continuous non malignant cell lines of DNP specific B lymphocytes developed in her laboratory and KLH specific T helper lymphocytes to determine if alcohol directly effects both B and TH cells. These cell lines will then be used to determine which stage of B cell and T cell response is inhibited by alcohol. After determining the time in the immune response when suppression occurs, the same in vitro systems will be used to compare the changes in phosphotidyl inositol pathway, cyclic AMP levels and Ca+2 influx and mobilization which occur in the presence and absence of alcohol at the point of suppression. Phospholipid methylation and phosphorylation of a 44 Kd protein will also be examined if suppression appears to involve the action of B cell stimulation Factor 1 or B cell differentiation factor mu. Changes associated with suppression by acute alcohol exposure will then be compared to changes induced by chronic alcohol exposure. Chronic alcohol exposure will be accomplished both in vivo by feeding alcohol mice and using spleen cells, and in vitro by growing the cell lines in the presence of alcohol.
