Simulation of parasite-induced gut hypersensitivity: implications for vaccination.
Antigenic challenge of jejunum from rats infected with Trichinella spiralis evokes a biphasic pattern of epithelial Cl- secretion, as measured in vitro by electrophysiological methods. Peaks of secretion occur at approximately 1.5 and approximately 5.0 min post-challenge. Challenge of jejunum from hosts passively immunized with serum containing anti-Trichinella anaphylactic antibody evokes the late phase but not the early phase of Cl- secretion. Since the early phase is mediated by 5-hydroxytryptamine and histamine from mast cells, we hypothesized that the failure to express that phase was due to a decrease in mast cell-derived mediators secondary to a deficiency in mucosal mast cell numbers. The hypothesis was tested by correlating mast cell numbers with patterns of antigen-induced Cl- secretion using several immunization regimes. Rats actively immunized by infection produced anti-Trichinella IgE and had a mucosal mastocytosis. Rats passively sensitized with serum containing anti-Trichinella IgE had normal numbers of mast cells in their mucosa. Inducing mastocytosis in rats, by infecting them with Nippostrongylus brasiliensis prior to passive sensitization with anti-Trichinella serum, primed for the expression of a biphasic Cl- secretory response upon subsequent challenge with Trichinella antigen. Rats actively sensitized by injection with Trichinella antigen elicited an IgE response without mastocytosis and expressed only the late phase of antigen-induced Cl- secretion. Results (i) support our hypothesis, (ii) emphasize the importance of the cellular state of the mucosa in the functional expression of local anaphylaxis; and (iii) provide a physiological explanation for the general failure of vaccination and passive sensitization to induce functional immunity equivalent to that induced by natural infection.
Harari
Y
Y
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.
Castro
G A
GA
D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D002712:Chlorides / Q000378:metabolism; D007114:Immunization; D007116:Immunization, Passive; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism; D007583:Jejunum / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D014234:Trichinella / Q000276:immunology*
D000947:Antigens, Helminth; D002712:Chlorides