The mammary gland and neonatal immunity

The newborn pig and calf are normally devoid of immunoglobulins at birth and rely on colostrum for serum antibody and milk for intestinal antibody during their early life. Colostrum and milk are well adapted to their different immunological roles. Colostrum immunoglobulin is derived almost entirely from the serum of the dam and after absorption by the neonate is destined here to provide serum antibody. The main immunoglobulin in pig's milk is IgA which predominates also in intestinal juice of the adult. Intestinal IgA is locally formed in the lamina propria of the intestinal tract, whereas milk IgA is locally formed in the mammary gland. It seems likely, however, that IgA production at both sites results from antigenic stimulation of the gut associated lymphoid tissue and the immune systems of these organs are intimately linked. The role of IgA in mucosal defence in the calf appears to be assumed by IgG. Colostrum and milk IgG₁ is derived from serum; nonetheless it is likely that the main antigenic stimulus for its formation is obtained from the intestinal tract—the mammry gland immune system is present and its artificial stimulation could prove to be of great practical value.

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Kurzfassung Schweine und Kälber besitzen bei ihrer Geburt normalerweise keine Immunoglobuline und sind daher in ihrem ersten Lebensabschnitt auf Kolöstrum zur Bildung von Antikörperserum sowie auf Milch zur Bildung intestinaler Antikörper angewiesen. Kolöstrum und Milch eignen sich ganz besonders für die verschiedenen von ihnen zu erfüllenden immunologischen Zwecke. Kolöstrum-Immunoglobulin wird fast ausschliesslich dem Serum des Muttertiers entnommen und ist nach seiner Absorption durch das Neugeborene zur Bildung von Antikörperserum bestimmt. Wichtigstees Immunoglobulin in der Schweinemilch ist das IgA, das auch in der Intestinalflüssigkeit erwachsener Tiere überwiegt. Intestinal IgA wird lokal in der Lamina propria des Intestinaltrakts gebildet, während Milch-IgA örtlich in den Mammadrüsen entsteht. Wahrscheinlich ist jedoch, dass an beiden Stellen die IgA-Bildung durch die Antigenstimulierung der mit den Eingeweiden verbundenen lymphoiden Gewebe bewirkt wird; die Immunsysteme beider Organe sind eng miteinander verknüpft. Bei der mukösen Abwehr im Kalb scheint die Rolle des IgA von IgG₁ übernommen zu werden. Kolöstrum und Milch-IgG₁ werden vom Serum abgeleitet; es ist jedoch wahrscheinlich, dass der für seine Bildung wichtigste Antigenstimulus aus dem Intestinaltrakt kommt, wohingegen das Immunsystem der Mammadrüsen bei Rindern umgangen wird. Dort besteht allerdings ein lokales Immunsystem der Mammadrüsen, und seine künstliche Stimulierung könnte sich als äusserst nützlich erweisen.

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Resume Le porcelet et le veau sont normalement dépourvus d'immunoglobulines à la naissance; ils dépendent du colostrum pour l'acquisition d'anticorps sériques et du lait pour celle d'anticorps intestinaux pendant les premiers jours de leur vie. Le colostrum et le lait sont bien adaptés à leurs différents rôles immunologiques. L'immunoglobuline du colostrum provient presque entièrement du sérum de la mère et, après absorption par le nouveau-né, lui apporte les anticorps sériques. La principale immunoglobuline contenue dans le lait de la truie est l'IgA, qui prédomine également dans le suc intestinal de l'animal adulte. L'IgA intestinale se forme localement dans la lamina propria du tractus intestinal, tandis que l'IgA du lait se forme localement dans la glande mammaire. Toutefois, il semble probable que la production d'IgA dans ces deux organes résulte de la stimulation antigénique du tissu lympholde associé à l'intestin et que les systèmes immunitaires de ces organes sont intimement liés. Le rôle joué par l'IgA dans la réaction de défense de la muqueuse chez le veau semble assuré par l'IgG₁. L'IgG₁ du colostrum et du lait est dérivée du sérum; néanmoins, il est probable que le principal stimulus antigénique présidant à sa formation provienne du tractus intestinal—le système immunitaire de la glande mammaire n'intervenant pas chez les bovins. Cependant, il existe un système immunitaire local de la glande mammaire et sa stimulation artificielle pourrait s'avérer très utile sur le plan pratique.

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Riassunto Alla nascita, il suino ed il vitello sono normalmente privi di immunoglobuline, e nel primo periodo di vita dipendono dal colostro per gli anticorpi del siero, e dal latte per quelli intestinali. Il colostro ed il latte sono biologicamente ben adattati ai loro diversi ruoli immunologici. L'immunoglobulina del colostro proviene quasi per intero dal siero della madre e, dopo l'assorbimento da parte del neonato, è destinata a fornire gli anticorpi del siero. La principale immunoglobulina contenuta nel latte di suino è la IgA, che predomina anche nel succo intestinale dell'adulto. L'IgA intestinale si forma localmente nei lamina propria del tratto intestinale, mentre l'IgA del latte si forma localmente nella ghiandola mammaria. Sembra tuttavia probabile che le produzione di IgA in ambedue i siti risulti da stimolazione antigenica del tessuto linfoide associato all'intestino, e che i sistemi immunitari di questi organi siano intimamente collegati. Il ruolo dell'IgA nella difesa della mucosa nel vitello pare sia assunto dalla IgG₁. L'IgG₁ del colostro del latte è ricavata dal siero; tuttavia, è probabile che il principale stimolo antigenico per la sua formazione derivi dal tratto intestinale—in quanto nel bovino il sistema immunitario della ghiandola mammaria viene scavalcato. Tuttavia, un sistema immunitario locale della ghiandola mammaria esiste e, qualora stimolato artificialmente, potrebbe dimostrarsi di grande utilità pratica.

     

乳腺免疫研究进展

乳腺生物反应器是现今生物学领域备爱关注的焦点。探索和研究乳腺免疫调节机制将有助于加快乳腺生物反应器产业化进展，作者综述了乳腺免疫特点、参与免疫反应的功能细胞与效应因子及其作用机制等方面的研究进展。     

The mammary gland and neonate mucosal immunity

The passive mucosal protection of neonate mammals is dependent on the continuous supply until weaning of maternally dimeric IgA (monogastric) and IgG1 (ruminants). This lactogenic (humoral) immunity is linked to the gut, the so-called entero-mammary link, because of the translocation of Ig (IgA and IgG1) or the emigration of IgA lymphoblasts from the gut into the mammary gland (MG); on the other hand, studies on the lymphocyte subsets in the MG of artiodactyls sustained the view of a true local immune response, depending on the MG stage development. Accordingly, the increase of the lactogenic immunity may focus on (1) inductor sites (gut and, possibly, the MG), (2) increase in cell traffic from the gut into the MG, and (3) enhancement at the effector site of the Ig production and excretion in milk. A specific mucosal environment (interleukins and hormones) is responsible for IgM/IgA switch, the induction of mucosal homing receptor onto lymphoblasts and mucosal vascular addressins; very few data are available for the mechanism of lymphoblasts recruitment, either IgA or IgG1, although lactogenic hormones have been implicated in the IgA-blasts homing into the mice MG. After weaning, the neonate is able to mount a gut immune response, but the shortage of the suckling period did not seem to be detrimental for its onset. In soyabean allergy, both piglet and calf exhibited gut villus atrophy, gut accumulation of IgA (swine) and IgG1 (cattle) immunocytes, sustaining the view that a specific environment in ruminant is responsible for both IgA and IgG1 production.     

Immunity in the mammary gland.

The ruminant mammary gland is an extremely important economic organ in that it provides a major nutrition source for a significant portion of the world's human population. The ruminant mammary gland is also responsible for providing protective immunity to neonates and for defending itself from invading pathogens. A wide array of humoral and cellular immune mechanisms are present in the mammary gland and actively participate in providing immunity to newborns and the mammary gland per se. The acute inflammatory response is essential in determining the outcome of intramammary challenge, and factors affecting innate and adaptive immunity in the context of mammary health are reviewed in detail. The ruminant mammary gland is also unique in that lymphocyte trafficking, which is essential to adaptive immunity, is shared with the peripheral immune system rather than the common mucosal immune system.     

Canine mammary gland tumors.

The National Consensus Group recommends that all women with tumors larger than 1 cm be offered chemotherapy regardless of tumor histology of lymph node status. This recommendation is to ensure that everyone at risk for failing, even though the risk may be low in women with relatively small tumors and favorable histology, has a choice and receives the benefit of adjuvant chemotherapy. This type of treatment recommendation may also be made in dogs based on recognized, well-accepted prognostic factors such as tumor size, stage, type, and histologic differentiation. Based on the limited clinical information available in veterinary medicine, the drugs that are effective in human breast cancer, such as cyclophosphamide, 5-fluorouracil, and doxorubicin, may also have a role in the treatment of malignant mammary gland tumors in dogs. Randomized prospective studies are needed, however, to evaluate the efficacy of chemotherapy in dogs with high-risk mammary gland tumors and to determine which drugs and protocols are the most efficacious. Until such studies are performed, the treatment of canine mammary gland tumors will be based on the individual oncologist's understanding of tumor biology, experience, interpretation of the available studies, and a little bit of gut-feeling. Table 2 is a proposal for treatment guidelines for malignant canine mammary gland tumors according to established prognostic factors, results from published veterinary studies, and current recommendations for breast cancer treatment in women.     

Biopsy of the bovine mammary gland.

A technique is described for biopsy of the bovine udder, employing sedation and local anaesthesia. Tissue samples of approximately 5 g were obtained by electrocautery from two quarters of the udder of a cow laterally recumbent. Care was taken to ensure complete haemostasis which was achieved by electrocoagulation and ligation. Postoperative recovery was rapid, and loss of yield was no greater in biopsied glands than in control glands of the same cow. Yield from all quarters returned to preoperative levels within 48 h.     

MHC class II expression in the bovine mammary gland.

The distribution of major histocompatibility complex (MHC) class II positive cells within the connective tissue and the epithelium of the involuted bovine mammary gland has been determined. The effect of intramammary administration of the antigens ovalbumin and formalin killed Streptococcus uberis on the distribution pattern has also been investigated. Infusion of formalin killed S. uberis increased cellular expression of class II antigens when compared with quarters either infused with ovalbumin, not infused at all, or from which minor pathogens had been isolated. The increased expression occurred particularly in the area of the gland cistern-secretory tissue junction.     

Fibrosarcoma affecting the mammary gland of a cow.

A highly malignant fibrosarcoma which arose in or close to the mammary gland of a 12 year old Ayrshire cow, with metastases in local lymph nodes, lungs, liver, kidney and adrenal glands has been described. The tumors were densely cellular and consisted of interweaving bands of fusiform cells with a high mitotic index. Infiltration of normal tissues and invasion of blood vessels were characteristic features. Ultrastructural study of the cells revealed mesenchymal cells with abundance of rough endoplasmic reticulum and cytoplasmic vesicles and they were closely invested with collagen fibers.     

Sexual dimorphism of the normal rat mammary gland.

Sexual dimorphism is a routinely encountered but previously unreported feature of the normal rat mammary gland. Forty male and 40 female F344 rats, 19 weeks of age, were examined retrospectively to document histologic differences that are very apparent when mammary glands of males and females of the same age are compared. Development of the mammary gland starts in utero, and there is reported to be little morphologic difference between males and females at birth. By 19 weeks of age, however, the differences are very noticeable. The mammary glands of females, comprised of scattered tubular ducts and alveolar structures that have distinct lumina lined, usually, by a single layer of cuboidal epithelium, are characterized as tubuloalveolar. In young males, mammary tissue is generally more florid than in females of the same age. There are, scattered within the hypodermis, larger, more contiguous, lobular groups of cells that are distinct for their lack of obvious tubular or ductal orientation. The cells, arranged into alveoli, are generally characterized by abundant, foamy, eosinophilic cytoplasm containing distinct, variably-sized vacuoles. Alveolar lumina are mostly indistinct but may contain evidence of secretory activity. To emphasize the importance of this difference, selected results of a routine toxicity study are discussed in which the mammary glands of male rats, exposed for 52 weeks to cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4- methyl-aminobenzamide, a reported dopamine antagonist, underwent distinctive histomorphologic changes. As a result of exposure to this compound, the lobuloalveolar structure described as normal for male rats assumed characteristics of a tubuloalveolar morphology indistinguishable from that seen in the unexposed females.(ABSTRACT TRUNCATED AT 250 WORDS)     

The expression of carbonic anhydrase in canine mammary gland and mammary gland tumor

Carbonic anhydrase (CA), a metallo-enzyme containing zinc, broadly distributes in mammalian tissues and participates in physiological regulation such as respiration, acid-base balance, ion transport, bone resorption, as well as the development of tumor by the reversible hydration of carbon dioxide. However the expression of CA in the tissue of mammary gland tumor was not documented. In this study we examine the histolocalization and gene expression of CA in both normal canine mammary gland tissue and mammary gland tumor by histochemical examination, and RT-PCR. Four mRNA expression of CA isoenzymes, such as CA II, IV, VI and IX were found under RT-PCR analysis and different band patterns were found between normal canine mammary tissue and canine mammary gland tumor tissue. CA II, IV, VI and IX gene mRNA expression were found in the normal mammary gland tissue, indicating CA II, IV, VI and IX are likely to be the essential enzymes to maintain the normal physiological condition of canine mammary gland tissue cells. However the expression of CA IV was not found in the tissue of malignant mammary gland tumor that may become the marker for the prognostic recognition of canine mammary gland tumor.     

Lectin histochemical characteristics of the canine female mammary gland.

Twelve biotinylated lectins and an avidin-biotin-peroxidase method were used to detect and localize specific carbohydrate residues on formalin-fixed, paraffin-embedded female canine mammary gland sections. Histologic sections from 3 lactating and 7 nonlactating mixed-breed dogs (age 5.6 +/- 0.35 years) were incubated with Arachis hypogea agglutinin (peanut agglutinin; PNA), Concanavalia ensiformis agglutinin (conA), Dolichos biflorus agglutinin (DBA), Glycine max agglutinin (SBA), Griffonia simplicifolia agglutinin-I (GS-I), Lens culinaris agglutinin (LCA), Lycopersicon esculentum agglutinin (LEA), Phytolacca americana mitogen (pokeweed mitogen; PWM), Ricinus communis agglutinin-I and -II (RCA-I and -II), Triticum vulgaris (WGA), and Ulex europaeus agglutinin-I (UEA-I). Each lectin had a specific binding pattern, except SBA and DBA. In nonlactating glands, PNA, conA, LEA, and UEA-I stained duct cells in a linear-binding pattern, with a mean percentage of positive ducts per section of 28.7 (+/- 0.6), 65.7 (+/- 0.3), 100 (+/- 0), and 8.4 (+/- 0.2), respectively. Strong apical, lateral, basal, and cytoplasmic positivity on duct cells was seen after incubation of the sections with RCA-I, RCA-II, and WGA in all ducts. In acinar cells, the binding pattern and the staining distribution of all the lectins studied were similar to those in duct cells. However, for PNA, conA, and UEA-I, the mean percentage of positive lobules per section was 33.7 (+/- 0.9), 62 (+/- 0.5), and 10.5 (+/- 0.2), respectively. In glands from lactating dogs, conA and UEA-I did not stain. The cytoplasm of all myoepithelial cells was moderately stained with RCA-I, RCA-II, and WGA.(ABSTRACT TRUNCATED AT 250 WORDS)