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The experiment comprised two sections. First, radiotracer techniques were used to study the metabolism of IgG1 and IgG2 in 5 non-pregnant and 4 pregnant ewes. In the pregnant ewes, the rates of synthesis for IgG1 and IgG2 were similar to the rates observed in non-pregnant animals. However, the irreversible loss of IgG1 was significantly greater than IgG2 in pregnant ewes and IgG1 in non-pregnant ewes. Additionally, it was found that most of the IgG1 and virtually all of the IgG2 in mammary secretion was serum derived. Secondly, the levels of sodium, potassium and lactose and the selective index for IgG1 in mammary secretions of 5 pregnant ewes were monitored over the parturient period. The values of all the measures remained relatively constant until one day before parturition. From one day pre-partum, the levels of potassium and lactose in mammary secretion began to increase and had risen 2-3 fold by 5 days post-partum. Over the same period, the selective index for IgG1 decreased 20 fold, wehreas the level of sodium fell from approximately 32 mmol/l to 18 mmol/l. The concentration of IgG1 in plasma slowly declined from approximately 23 g/l to 15 g/l over the last 10 days of pregnancy. During the parturient period, the decline in plasma IgG1 levels, in comparison with IgG2, without alteration in the rates of synthesis of either immunoglobulin, supports the hypothesis that selective transport of IgG1 into mammary secretion occurs without degradation. The results also indicate that the transport of sodium and potassium into mammary secretions are altered over the parturient period.

The significance of local effects associated with mammary involution on transfer of immunoglobulin and especially on the selective transfer of IgG1 into mammary secretion of cows approaching parturition has been determined. This was carried out by measuring the changes in the concentration of IgG1, IgG2, IgM and IgA in serum and mammary secretion of 5 cows in which two mammary glands were milked continuously (twice daily) during the period preceding parturition, while the other two glands were allowed to undergo normal involution. In the secretion of unmilked glands of all cows there was a substantial increase in the concentration of IgG1 as cows approached parturition. In contrast, the increases in the concentration of IgG1 and in the selective index for IgG1 of milked glands were either virtually non-existent (1 cow) or generally reduced in magnitude and delayed in time of onset (4 cows). It is clear from the results that continued milking of a mammary gland throughout pregnancy tends to maintain milk production in the milked gland and at the same time reduces the massive selective transfer of IgG1 into secretion of that gland.

Various immunoglobulins were labelled with radioactive iodine and their distribution between intestinal lymph and plasma followed in order to determine the origin of the immunoglobulins found in intestinal lymph. By comparing specific activities in plasma and lymph, it was computed that 25 percent of the IgG1 and IgG2 and 90 percent of the IgA in intestinal lymph were locally synthesised. The results suggest that virtually all of the IgA and a proportion of the IgG1 computed to be synthesised locally were derived from plasma cells of corresponding specificity in the lamina propria of the intestine.

A comparison was made of the antibody-containing cell (ACC) response in hepatic and intestinal lymph of sheep following intraperitoneal injection of ovalbumin in Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA) or the bland vegetable oil preparation, adjuvant 65. There was a substantial ACC response in intestinal lymph following intraperitoneal injection of ovalbumin in either FCA or FIA. Responses were essentially similar in magnitude and for both adjuvants ACC were distributed mainly among the IgGl, IgA and IgM immunoglobulin classes. In contrast, there was a negligible ACC response in intestinal lymph following injection of antigen in adjuvant 65. The output of ACC in hepatic lymph and the immunoglobulin class distribution of the ACC following intraperitoneal injection of antigen in either FCA or FIA were similar and results were specificity comprising 32% of ACC at the peak of the response. In contrast to results for intestinal lymph, injection of antigen in IgGl- and IgM-specific cells in hepatic lymph. The ACC response was much smaller in magnitude than with the Freund's adjuvants. Intravenous injection of ovalbumin in FIA or adjuvant 65 gave rise to substantial ACC responses in hepatic lymph which contrasted with the barely detectable response in intestinal lymph. Following intravenous administration the great majority of ACC in hepatic lymph were of the IgM class irrespective of adjuvant used although ACC of the IgA class made a transitory appearance.

The output and immunoglobulin class of antibody-containing cells (ACC) in lymph from different regions of adult sheep has been compared following intraperitoneal or subcutaneous injection of ovalbumin in Freund's complete adjuvant (FCA). Intraperitoneal injection of antigen in FCA elicited no response at all in popliteal lymph, but there were substantial responses in lymph from the hepatic, coeliac (which carries lymph mainly from the abomasum and anterior duodenum) and intestinal lymphatic ducts. A significant increase in the number of blast cells accompanied the ACC response. ACC reached a peak 7- days after injection when ACC comprised 3.7% +/- 0.7%, 2.3% +/- 0.7% and 3.3% +/- 0.6% of total lymphocytes in lymph from the hepatic, coeliac and intestinal ducts respectively. At this time ACC were distributed among three immunoglobulin classes IgM, IgG1 and IgA with the latter constituting 25%--40% of ACC in lymph from the three regions. ACC did not appear in intestinal lymph following subcutaneous injection of ovalbumin in FCA in the leg immediately below the tarsus. This contrasted with the vigorous response in popliteal lymph where 6 days after the injection ACC constituted 3.9% of cells in lymph. Most (83%) of the ACC were IgG1-specific at the peak of the response. The remaining ACC were distributed among the IgM, IgG2 and IgA classes with the latter comprising 3% of total ACC.

Immunoglobulins in mammary secretion are derived from blood serum or are made locally by cells of the lymphocyte-plasma cell series situated close to the glandular epithelium. The major immunoglobulin in colostrum and milk of ruminants, IgG1, is derived from the blood and is transferred into secretion selectively relative to IgG2, probably by a mechanism requiring specific receptor sites on the basal of intercellular membrane of the glandular epithelium. Acute inflammation causes suppression of selective transfer of IgG1, but there is a marked increase in the transfer of proteins, such as IgG2 and serum albumin, which enter secretion nonselectively. Infusion of antigen into the mammary gland of ruminants some weeks before parturition induces a persisting local production of antibody, most of which is associated with IgA and IgM. IgA cells in the mammary gland probably originate in the intestine, and prior antigenic stimulation of the gut may be required for maximal IgA antibody responses in the gland. Local immunization with staphylococcal vaccines gives a measurable degree of protection against staphylococcal challenge. Systemic immunization with viable staphylococci leading to subcutaneous abscess formation elicits significant protection to subsequent mammary challenge which is attributable, at least in part, to specific antibody of the IgG2 class cytophilic to polymorphs.

A comparative study was made on the secretion of IgG1 and IgA into parotid and submaxillary saliva of sheep. The purpose of the study was to examine the suggestion that in the external secretory organs of ruminants there is an inverse relationship between the capacity to selectively transfer IgG1 and the development of the IgA secretory system. Despite a marked difference in the secretion of IgA between the parotid and submaxillary salivary glands, the magnitude of selective transfer of IgG1 was similar. Thus, there appears to be no relationship between the selective transfer of IgG1 and the secretion of IgA into the saliva of sheep.