Influence of lipopolysaccharide on graft versus host reactivity of lipopolysaccharide-unresponsive C3H/HeJ mice.

It was initially reported that lipopolysaccharide (LPS)-unresponsive C3H/HeJ mice are refractory to LPS at the B-lymphocyte level, but more recently it has been shown that other cells are similarly unaffected. The current study was undertaken to study an in vivo LPS-modulated disease process involving macrophage-T cell interactions. Adult CBA/J and C3H/HeJ mice were used as spleen donors, and graft versus host reactions were induced in BALB/c neonates. Prior LPS treatment of CBA/J adults decreased the ability of their spleen cells to cause fatal graft versus host disease in BALB/c neonates, whereas no difference was found between injection of spleen cells from normal or LPS-treated C3H/HeJ mice. Similar results were obtained with these cell types when the mouse spleen mixed leukocyte culture system was used. In a carbon clearance assay for stimulation of the reticuloendothelial system with LPS, it was found that the rate of phagocytosis was significantly increased in BALB/c and CBA/J mice 72 h after inoculation of LPS. No stimulation was seen in rate of carbon uptake in the C3H/HeJ animals after treatment with phenol-extracted LPS or with butanol-extracted LPS. An LPS-induced protective serum factor was produced only in the LPS-responsive CBA/J mice and was specific for the syngeneic cells.

Experimental neonatal colibacillosis in cows: immunoglobin classes involved in protection.

Pregnant cows were vaccinated with one of four vaccine preparations to induce passive immunity in their offspring against a homologous oral challenge with Escherichia coli strain B-44. Quantitative assays of specific antibody in colostral whey from both immunized and nonimmunized dams revealed that immunoglobulin G, immunoglobulin A (IgA), and immunoglobulin M (IgM) with anti-O (somatic) activity were present in whey of all dams tested, whereas a marked deficiency of IgA and IgM anti-K immunoglobulin was noted in the whey from control dams only. The degree of scours (neonatal colibacillosis) induced by oral challenge was evaluated clinically and reported by a semiquantitative scour index as 0 to 4+. Calf scour indexes showed an inverse relationship to the frequency of occurrence and to the levels of IgA and IgM in whey of dams vaccinated with killed vaccine, live vaccine, and culture supernatant, and from nonvaccinated controls. The data strongly suggested that IgA and colostral IgM anti-K immunoglobulins were important in passive immunity in experimental neonatal bovine colibacillosis.

Experimental neonatal colibacillosis in cows: serological studies.

Serological studies of passive immunity in experimentally induced bovine colibacillosis was studied in a 41-cow university herd. Pregnant dams were antigenized prepartum with two injections administered by the subcutaneous and intrammamary routes with one of four vaccine preparations (killed bacteria, live bacteria, culture supernatant, or heart infusion broth [control]). The data indicate that 77% of the neonates born to vaccinated dams were strongly protected against oral challenge with Escherichia coli strain B-44. Bacterial agglutinin and passive hemagglutination titers of colostral whey directly reflected the efficacy of the vaccines. A notable decrease in the whey titers to somatic and capsular antigens occurred after heat treatment at 56 C for 30 min. Complicity of heat-liable immune factor(s) in protection from scouring was suggested. The nature of the protective antigen is not clearly defined by these studies but there is some evidence that the K antigen may play a vital role in this regard.

Studies on the immune response of congenitally athymic (nude) mice.

The central role of the thymus in immunity was assessed in nude mice. Nudes failed to reject allografts and xenografts and to respond to foreign erythrocytes but responded normally to endotoxin and pneumococcal polysaccharide. Thymus reconstitution was demonstrated in vivo and in vitro whereas reconstitution with thymic humoral factors or polyanions was not detected. Coliform overgrowth and depressed IgA levels in nudes appeared to contribute to wasting. These data emphasize the need for thymus participation in many immune phenomena.

Immunosuppression of mice injected with heterologous anti-immunoglobulin heavy chain antisera.

Neonatal injection of mice with rabbit anti-micro antiserum has been shown to produce complete loss of direct and indirect plaque-forming responses to sheep erythrocytes as well as loss of serum IgM and severe depressions of all other serum immunoglobulins. Similar injection of anti-gamma1gamma2 or anti-gamma1 antibodies effects a loss of the indirect response but induces relatively minor alterations in serum Ig levels. Delaying initiation of anti-micro treatment until young adulthood results in a somewhat diminished effect on plaque-forming responses and serum Ig levels but triggers the release of high serum levels of an aberrant micro-bearing protein. Anti-micro suppression of genetically thymusless mice indicates that at least part of the target cells for suppression are bone marrow derived. A working hypothesis for the maturation of humoral antibody-producing cell lines as it relates to these data is discussed.