Gut immunology in fish: a review.

During recent years considerable study has been made of the systemic immune system of fish, although less attention has been paid to local immunity at sites such as the gut, reproductive tract and skin. Recent work on the structure of gut-associated lymphoid tissue and other intestinal cell populations, the absorption of macromolecules from the intestinal lumen and the production of specific mucosal antibodies strongly suggests, however, that the gut of these lower vertebrates is immunocompetent. This review briefly deals with current concepts on the nature of gut-associated lymphoid tissues and other cell populations in the gut, intestinal and biliary immunoglobulin (Ig), antigen uptake and the significance of oral vaccination in the protection of commercially reared fish against infectious disease.

Ontogeny of gut-associated lymphoid tissue (GALT) in the dogfish Scyliorhinus canicula L.

Cartilaginous fish occupy a fundamental position in vertebrate phylogeny and it is likely that this group has retained some of the ancestral immune mechanisms. The ontogeny of GALT has received little attention in elasmobranchs and this study correlates this development with morphological differentiation, development of other lymphoid organs, exposure to seawater and transition from yolk dependence to exogenous food as a source of nutrient. GALT was first represented by individual lymphocyte-like and macrophage-like cells in the lamina propria. In later stages accumulations and intraepithelial leucocytes were recorded prior to hatching. The size of accumulations and the number of lymphocyte and macrophage-like cells infiltrating the lamina propria and epithelium increased in fish as they became dependent upon an exogenous diet. Although GALT developed after the thymus and lymphoid-like tissue in the kidney and at approximately the same time as the epigonal, Leydig and spleen, the source of cells populating the gut is unknown. Plasma cells and granulocytes were not observed in the developing fish until 6 months post-hatch after which the fish had a similar GALT distribution and content to the adult fish.

Mechanism by which antibodies to non-AgB antigens mediate rejection of rat leukaemia cells.

The August and Hooded rat strains are compatible at the major histocompatibility locus (both are AgB5 or Rtlc). Antisera against the minor histocompatibility antigens of Hooded rats were raised by immunizing August rats with grafts of tumours or normal tissue. Such antisera, if transferred to normal unimmunized August rats, cause them to reject i.v. administered Hooded rat leukemia (HRL) cells within a few hours, and X-irradiated August rats, for whom a graft of HRL is lethal, can survive indefinitely if pretreated with the antiserum. The distribution of 125I-labelled HRL cells in the tissues of August rats was followed at times after their injection, and it was found that, in the presence of antiserum, i.v. administered leukaemic cells are rapidly destroyed in the liver and spleen. The active component of the antiserum is IgG antibody, and its action is independent of the lytic elements of complement. Antibody-mediated splenic and hepatic clearance of the leukaemia cells is unaffected by total-body X-irradiation but reduced by treating the rats with colloidal carbon. The data are consistent with the hypothesis that the rejection of HRL across the histocompatibility barrier studied is, in the presence of antibody, effected by immunophagocytosis.

Immunogenicity of a rat leukaemia of spontaneous origin (SAL).

The SAL rat leukaemia, which resembles acute myeloblastic leukaemia, appeared initially to be non-immunogenic since resistance to an i.p. challenge with as few as 100 cells could not be obtained using stimulation of the RES or by immunization with SAL cells exposed to x-rays, nitrogen mustard, iodoacetate or glutaraldehyde. However, immunization with SAL cells exposed to low doses of mitomycin-C slowed the growth of the challenge inoculum. Cells treated with high doses of mitomycin-C did not immunize. The results are interpreted in terms of rapid shedding of a tumour-specific antigen from the membrane of SAL cells.

Cross reactivity of an alloantigen present on normal cells with the tumour-specific transplantation-type antigen of the acute myeloid leukaemia (SAL) of rats.

Resistance can be induced in the syngeneic host (August rats) to a myelogeneous leukaemia of spontaneous origin, called SAL, by immunization with allogeneic cells derived form both normal and malignant tissues obtained from the Hooded rat strain. Serological experiments support the conclusion that the antigen involved-referred to as "Ho-SAL"-has the properties of a tumour specific transplantation-type antigen for SAL cells but is a widely expressed alloantigen found in both normal and malignant cells derived from Hooded rats. Antisera to it can be raised in Wistar rats.

The growth patterns of two transplantable acute leukaemias of spontaneous origin in rats.

The growth pattern and morphology of two transplantable acute leukaemias which arose spontaneously in pure line rats are described. They differ morphologically and on the basis of their behaviour in vivo, such as infiltration of lymphoid organs and presence in thoracic duct lymph, the leukaemia syngeneic to the August strain (referred to as the SAL) appears to be of myeloid type whereas the leukaemia syngeneic to the Hooded strain (referred to as the HRL) resembles acute lymphoblastic leukaemia. The HRL cells, but not the SAL cells, are lysed by murine anti-theta serum plus complement. These two transplantable acute leukaemias appear to be useful animal counterparts ot the human acute leukaemias and may be valuable models for studies on chemotherapy and immunotherapy.

Evidence of cytotoxic T and B immunoblasts in the thoracic duct of rats bearing tumour grafts.

Wistar rats were immunised with allogeneic or xenogeneic tumour before collection of their thoracic duct lymph. Specifically cytotoxic effector cells were found in the lymph between 3 and 8 days after immunisation, and their occurrence coincided with an increased number of immunoblasts in the lymphocyte population. The immune response in lymph to allogeneic cells appeared to be affected solely by radiosensitive thymus-dependent lymphocytes; no complement-dependent killing was evident and cytotoxic cells failed to appear when immunised animals were deprived of thymus-dependent lymphocytes. In contrast, the response to immunisation with xenogeneic cells elicited both complement-dependent and complement-independent cytotoxicity, but only the former could be detected in animals deprived of thymus-dependent lymphocytes. In normal animals and in animals deprived of thymus-dependent cells, the cytotoxic cells in the thoracic duct lymph appeared to be large lymphocytes or immunoblasts.