key: cord-0942367-fexqvtd7 authors: Besser, T. E.; McGuire, T. C.; Gay, C. C. title: The transfer of serum IgG1 antibody into the gastrointestinal tract in newborn calves date: 1987-12-31 journal: Veterinary Immunology and Immunopathology DOI: 10.1016/0165-2427(87)90126-7 sha: ddd6f2f3befe7f5cbd015fef0cd587fd4d78b82e doc_id: 942367 cord_uid: fexqvtd7 Abstract Transfer of functional blood IgG1 to the gastrointestinal tract was measured in neonatal calves. Radiolabelled immunoglobulin G1 (IgG1) anti-DNP antibody was administered to 2 day old calves by intravenous injection. The serum clearance rate was measured and was compared to the rate of protein-bound 125I excretion in the feces over a 10 day period to determine the importance of transfer to the gastrointestinal tract as a mechanism of serum IgG1 clearance. The amount of protein-bound and DNP-binding 125I present in the gastrointestinal tract of 10 day old calves at necropsy was also measured. Fecal excretion of protein-bound 125I accounted for 32% of the serum 125I-IgG1 clearance. Protein-bound 125I was present in the gastrointestinal tract at necropsy in amounts estimated to account for 68% of the total 125I-IgG1 clearance, and retained 65% of the DNP-binding ability of the original antibody. The discrepancy between the fecal excretion (32% of total IgG1 clearance) and the GI clearance estimated from protein-bound 125I in the gut (68% of total IgG1 clearance) is explained in part by IgG1 proteolysis occurring after transfer to the gastrointestinal tract but before fecal excretion. These results indicate that transfer to the calf gastrointestinal tract accounts for most IgG1 clearance in young calves, and that the intestinal antibody retains antigen binding function and may contribute to intestinal immunity. Calves are born essentially devoid of circulating immunoglobulin but are capable of absorbing large amounts of maternal immunoglobulin from colostrum on the first day of life (Pierce, 1962; Butler, 1969) . There is considerable variation in the efficiency of this absorption, and a given population of calves will exhibit a broad range of passive serum immunoglobulin concentrations. This is significant because calves with low circulating passive immunoglobulin levels are more susceptible to a number of infectious disease processes (Gay 1983) . The relationship between low serum immunoglobulin concentrations and high enteric disease morbidity and mortality rates during the first month of life (Gay 1983) suggests that circulating immunoglobulin has an effect on gastrointestinal tract immunity in calves. IgGl must be prominent in this protection; it is the predominant immunoglobulin in colostrum, and with its relatively long serum half life (approximately 18 days) it is the only passively acquired immunoglobulin persisting in substantial amounts throughout the period of high susceptibility to neonatal enteric disease. Enteric disease in neonatal calves is most frequently associated with a number of ubiquitous enteropathogens (rotavirus, coronavirus, cryptosporidium, for example) to which older animals are apparently resistant (Morin et al., 1978; Moon et al., 1978) . Many infected calves remain asymptomatic, but some individuals develop moderate to severe enteric disease. Calves with high serum immunoglobulin concentrations following colostrum feeding on the first day of life subsequently have lower rates of overall enteric disease morbidity and mortality (Fisher and de la Fuente, 1972; Fisher et al., 1975; Hurvell and Fey, 1970; Blom, 1982; Penhale et al., 1970; Boye et al., 1974; Gay et al., 1965 . Most studies demonstrating the protective effect of high serum passive immunoglobulin levels have not determined the specific etiology of the observed enteric disease, but specific effects on disease caused by bovine rotavirus (McNulty et al., 1976) and by enteric salmonella (Fisher et al., 1976) infections have been observed. Seemingly, passively acquired serum immunoglobulin, in particular IgGl, influences the occurrence and severity of infectious enteric disease in calves during the first month of life. ThSs association is not simply a correlation between protective lactogenic antibody and colostral antibody content, since a number of studies have involved market calves not nursing their own dams, or have involved calves fed artificial milk replacer (Hurvell and Fey, 1970; Penhale et al., 1970; 8oyd et al., 1974) . In these situations, dietary (milk) antibody content is not related to the antibody content of the colostrum ingested by the calf. For circulating IgG1 to affect enteric immunity, transfer of the immunoglobulin into the gastrointestinal tract would presumably be required. Serum IgG1 does appear in the gut lumen: Newby and Bourne (1976) determined that a significant percentage of the IgG1 in normal calves' intestinal contents is serum-derived, and that more serum-derived IgG1 is present in the intestines of calves with higher serum IgG1 concentrations than in calves with lower serum IgGl. Consistent with this observation, Saif and Smith (1985) observed that calves with high serum rotavirus antibody titers have persistent fecal rotavirus antibody titers after cessation of colostrum feeding. In addition, enteritis increases the rate at which serum proteins, including immunoglobulins, appear in the feces (Fisher et al., 1975; Marsh et al., 1969) , and immunoglobulin has a shorter serum half-life in animals with diarrhea (Macdougall and Mulligan, 1969) . Because of the relationship between serum immunoglobulin status and enteric disease, it is of interest to know the concentration of immunoglobulin in the gastrointestinal tract secretions of calves with different serum immunoglobulin levels. Quantitation of immunoglobulins in ruminant gastrointestinal secretions has produced conflicting results (reviewed by Butler, 1983 and Morgan et al., 1981) . In young calves, for example, Newby and Bourne (1976) determined that IgG1 decreased from 95% to 48% of intestinal immunoglobulin between two and fourteen weeks of age, while Porter et al. (1972) We used intravenously-injected 1251-1abelled IgG1 to quantitate the passage of serum IgG1 into the gastrointestinal tract (Besser, 1986) . The discrepancy between IgG1 transfer to the gut measured by fecal excretion (32% of the total IgG1 clearance) and the transfer estimated from protein-bound 1251 in the gut at necropsy (68% of the total IgG1 clearance) may be explained by IgG1 proteolysis occurring after transfer to the gastrointestinal tract but before fecal excretion. The occurrence of such proteolysis was demonstrated by Feeding 48-hour-old calves 1251-1gG1. The calves did not absorb measureable IgG1 (protein-bound 1251) to serum and yet excreted only 28% of the 1251 dose as protein-bound label in the Feces. The remainder was excreted as non-protein bound 1251 in the urine. The fraction of circulating, labelled IgG1 transferred daily into the GI tract was similar in calves with a wide range of Serum IgG1 concentrations. This agrees with the finding of Newby and Bourne (1976) In older cattle and in other species, transfer to the intestine ,nay also account for a substantial amount of IgG clearance and may contribute to intestinal immunity. The similar half-life of IgG1 in calves and in alder cattle suggests that a similar clearance mechanism is operating (Butler, !983; Nielsen et al., 1978; Husband et al., 1972) . IgG transfer to the intestine has also been reported in other species: mouse (Fubara and Freter, 1972) , rat (Wu and Walker, 1976) , rabbit (Fubara, 1972; Wernet et al., 1976) , dog (Anderson et al., 1963; Pierce and Reyqoldc, 1974) , and sheep Cripps et al., 1974) . In si~eep, Cripps et ~l. (1974) deter:nined that bloodderived IgG makes a significant contribution to the total intestinal IgG. In the dog, radiolabelled IgG transfer into intestinal loops occurred at a rate that explained most [gG clearance (Anderson et al., 1963) . Most major enteropathogen infections result in serum IgG antibody formation as part of the body's immune response. If intestinal transfer is a major route oF serum IgG clearance and if the transferred antibody retains function, serum-derived IgG may make a significant contribution to the intestinal immunity. Gamma globulin turnover and intestinal degradation of gamma globulin in the dog Antibody transferred from the blood to the gastrointestinal tract and its role in enteric immunity of neonatal calves The relationship between serum immunoglobulin levels and incidence of respiratory disease and enteritis in calves. 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