Immune Response in the Bovine Mammary Gland After Intestinal, Local, and Systemic Immunization

Abstract

The immune response in mammary glands of cattle was measured after intestinal, local, and systemic immunization with T4 bacteriophage. Nonlactating pregnant cows were immunized by infusions into the intestine or mammary gland and by subcutaneous injections in the region of the prescapular or external inguinal lymph nodes. Titers of antibodies of different isotypes were measured in serum and in lacteal secretions by enzyme-linked immunosorbent assay, and numbers of cells producing antibodies of each isotype were determined in lacteal secretions by the Jerne plaque assay. Substantial increases in immunoglobulin G subclass 1 (IgGl) and IgG2 antibody titers were detected in serum and lacteal secretions of animals immunized through an intestinal fistula. IgM and IgA antibody responses were low or undetectable. Low numbers of IgA and IgGl plaque-forming cells were occasionally detected. It is proposed on the basis of these data that migration of antigen-stimulated IgG lymphoblasts, and perhaps of antigen, to spleen and peripheral lymph nodes may be dominant events after intestinal immunization of ruminants. This is consistent with the predominance of serum-derived IgG antibodies in colostrum and milk. Intramammary infusion of antigen gave rise to increases in antibody titers in all classes which were greater not only in lacteal secretions but also in blood serum than with either systemic route used. There was clear evidence from relative antibody titers for local synthesis of antibodies, principally IgA and IgGl, in the immunized glands. Comparison of IgA titers in secretions from the immunized glands with those in serum also suggested that locally synthesized IgA antibodies may have contributed in some measure to serum titers. Local synthesis in both immunized and nonimmunized glands was also reflected by the presence of increased numbers of IgA and IgGl plaque-forming cells. It is hypothesized that antibody-forming cells responsible for local synthesis originated in lymphoid tissue within the mammary gland or from peripheral lymph nodes, depending upon the route of immunization.During the past decade important advances have been made in understanding migration patterns of B lymphoblasts within the secretory immune system. Antibody-forming precursor cells from Peyer's patches give rise in rabbits to plasma cells synthesizing immunoglobulin A (IgA) in the lamina propria of the intestine (7,8,34,35) as well as in the bronchi (34). A reciprocal migration was observed by cells from bronchusassociated lymphoid tissue (34). In several species, including humans, rats, rabbits, and swine, oral immunization during pregnancy has been shown to result in the presence of antibodies, predominantly IgA, in colostrum and milk (3,13,24,25,36). Oral immunization of women with Escherichia coli resulted in a marked increase of cells forming 0 antibodies of the IgA class in preparturient lacteal secretions and in colostrum t Present address:

Enteric Viral Infections of Calves and Passive Immunity

“…The source of elevated IgG1 oolostral and milk antibodies in these two studies is unclear. The former study demonstrated few IgGI producing cells in mammary secretions in spite of the predominately IgG1 response (13). A possible explanation might be that IgG1 plasma cells, which occur in relatively large numbers in the intestines of adult ruminants (46), contribute IgG1 antibodies (with specificity to enteric antigens) to serum and these then are transported actively to colostrum and milk.…”

“…In another study, jejunal infusion of pregnant cows with a nonreplicating bacteriophage antigen elicited IgG1 and IgG2 but not IgA antibodies in serum and mammary secretions (13). We found similar results in a preliminary study of oral administration of live virulent bovine rotavirus to five pregnant rotavirus seropositive cows; only IgGl rotavirus antibodies were elevated in mammary secretions of two of five cows (L. J. Sail, K. L. Smith, and D. R. Redman, unpublished observations).…”

Phage therapy: What factors shape phage pharmacokinetics and bioavailability? Systematic and critical review

“…Antibodies specific to phage virions have been by far the most frequently investigated and acknowledged part of mammalian immune reactions to phages. Their induction after phage administration has been observed in animal models 19,38,50,100,118,175,[184][185][186][187] and in humans. 131,188,189 Phage-specific antibodies may also rise from natural contact with phages that are ubiquitous in the environment and phages in human or animal bodies which make up the natural phageome.…”

The Mammary Gland in Mucosal and Regional Immunity

“…Moon and McDonald (1983) failed to find antibodies in milk when cattle were orally vaccinated with E. coli K99 and Harp and Moon (1988) found that most 51 Cr-labeled lymphocytes from the intestinal lymph nodes of cattle and sheep returned to the mesenteric-lymph node of intestine, whereas in parallel studies homing of such cells to the lymph node of the MG of sows was observed . However, some cell or antigen traffic must occur because Chang et al (1981) recovered IgA and IgG1 plaque-forming cells specific to T 4 -phage from the bovine MG after intestinal infusion of T 4 . Thus, the substantial cellular gut-mammary gland axis seen in rodents, primates, and swine appears to be lacking in ruminants.…”