Enhanced triggering of mucosal immune responses by reducing splenic phagocytic functions.

The role of the spleen in the rat mucosal immune response was investigated to three structural different pneumococcal polysaccharides, type 3, 4, and 14. Following immunization with pneumococcal polysaccharides, a larger amount of free antigen was found in several lymphoid tissues and an increased trapping of immune complexes was seen in follicles of splenectomized animals, as compared to control animals. Thus, clearance of the polysaccharides seems to be less effective after splenectomy. An increase in specific IgA antibody-containing cells (ACC) was found in mesenteric lymph nodes, villi and Peyer's patches in splenectomized rats. Apparently, splenectomy and subsequent decreased clearance of the antigen causes a prolonged stay of the antigen in the system and therefore specific ACC can be induced in different lymphoid tissues. After splenectomy the specific IgM and IgG antibody titers in serum decreased significantly for pneumococcal polysaccharides types 4 and 14, but not for type 3. Furthermore, the serum IgA antibody titers against the three types of polysaccharides under study were not affected. After elimination of macrophages in the spleen by treatment with dichloromethylene diphosphonate liposomes no ACC against type 14 were evoked in the marginal zone of the spleen, and again, an increase was observed in specific IgA ACC in mucosa-associated lymphoid tissues. The IgA antibody titers were also enhanced. In conclusion, IgA responses against pneumococcal polysaccharides can be elicited in absence of the spleen, i.e. at mucosal sites or in the draining lymph nodes. Furthermore, polysaccharide-specific IgA responses are enhanced after reduction of splenic phagocytic functions.

Effect of mucosal and systemic immunization with pneumococcal polysaccharide type 3, 4 and 14 in the rat.

Four immunization routes were investigated to induce an immune response against three structurally different types of pneumoccoccal polysaccharide (PPS) in the rat. In particular, the contribution of the IgA isotype in these immune responses was studied. Six days after administration of PPS type 3, 4 or 14, the localization of specific antibody-containing cells (ACC) in different lymphoid tissues and the antibody titres in serum were studied. All four routes induced anti-PPS ACC in the spleen. After intraduodenal, intravenous and especially intraperitoneal administration of PPS, many IgA-specific anti-PPS ACC were also found in parathymic and mesenteric lymph nodes and in the lamina propria of intestinal tissue. Several anti-PPS ACC were found in Peyer's patches, located peripheral of the B-cell areas. The intratracheal immunization elicited only a local immune response, in bronchus-associated lymphoid tissues and paratracheal lymph nodes. The localization of these anti-PPS ACC was influenced by the route of immunization. After all four investigated routes, specific antibodies were found in serum against PPS. However, some remarkable differences between PPS-3, 4 and 14 were found in the magnitude of the immune response and the distribution of the isotypes. Both route of immunization and structure of the PPS have a profound influence on the immune responses in rats.

Role of cAMP in electrical and secretory activity of the neuroendocrine caudo-dorsal cells of Lymnaea stagnalis.

The peptidergic neuroendocrine caudo-dorsal cells (CDC) in the cerebral ganglia of the freshwater snail Lymnaea stagnalis L. produce an ovulation-stimulating neurohormone (CDCH). Release occurs by exocytosis in a calcium-dependent way from axon terminals in the periphery of the intercerebral commissure, particularly during a period of electrical activity (the 'discharge'). An important factor in electrical and, hence, secretory activity of the CDC appears to be cyclic adenosine 3', 5'-monophosphate (cAMP). Incubation of cerebral ganglia in snail Ringer with the cAMP-analogue 8-(4-chlorophenylthio)-cAMP (cpt-cAMP) or with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) leads to activation of the CDC: electrophysiological, quantitative electron microscopic and bioassay studies show that incubation results in the onset of intense electrical activity, a marked reduction in the number of secretory granules in the axon terminals, an enormous increase in the number of exocytosis phenomena and a strong stimulation of CDCH-release. It is assumed that treatment with IBMX or with cpt-cAMP mimics a rise in the cytoplasmic level of cAMP when the CDC become activated by a physiological stimulus. This rise most likely effectuates a permeability change of the axolemma for ions involved in the discharge. As a consequence of the depolarization of the axolemma during the discharge, calcium ions would enter the axon terminal and induce exocytotic release of CDCH.