Submitted to: Flemish Veterinary Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 9, 2000
Publication Date: April 9, 2000
Citation: Paape, M.J., Shafer-Weaver, K., Capuco, A.V., Oostveldt, K.V., Burvenich, C. 2000. Immune surveillance of mammary tissue of lymphocytes and phagocytic cells. Flemish Veterinary Journal. 480:257-277.
Interpretive Summary: Bacterial invasion and growth within the mammary gland is the main cause of mastitis. Invading bacteria settle next to the epithelial cells lining the mammary ducts, absorbing nutrients from milk while expelling harmful toxins that attack and destroy the epithelium. White blood cells called macrophages soon release chemical messengers called cytokines that signal the body for help. Soon PMN, a specialized form of white blood cells, migrate directly from blood into the bacterial hoard. The PMN combats the bacteria directly by ingestion or phagocytosis, aided by antibodies that attach to the bacteria and allow the PMN to recognize them as foreign. For the PMN it is a dead end mission. After ingestion and release of their chemicals most of the PMN perish. Next macrophages migrate in through the pores of the capillaries. Damage to the epithelium is limited by induction of programmed cell death (apoptosis) in PMN and their engulfment by macrophages. Through this process damaging chemicals are walled off withi dying PMN that are then ingested by macrophages to minimize damage to the epithelium of the udder. Within several hours lymphocytes arrive at the site of the infection and take the battle to another level of immunological defense, as they recognize antigens through membrane receptors that are specific for invading pathogens. Soon the balance of the struggle is tipped away from the invading bacteria. However, vast areas of the epithelium have been destroyed. Extensive scarring will result in a loss of secretory epithelium and milk production will never again reach normal levels. If all of the bacteria are not completely destroyed, the cellular drama becomes chronic and a subclinical form of the disease may continue for the remainder of lactation.
The cells in milk consist of lymphocytes, neutrophil polymorphonuclear leukocytes (PMN), macrophages and epithelial cells. In mammary quarters free from bacterial infection macrophages are the predominate cell type (35 - 79%), followed by PMN (3 - 26%), lymphocytes (10 - 24%) and epithelial cells (2 - 15%). In infected mammary glands the percentage of neutrophils can approach 100%. Lymphocytes together with antigen-presenting cells function in the generation of an effective immune response. Lymphocytes are the only cells of the immune system that have specificity as they recognize antigens through membrane receptors that are specific for invading pathogens. The professional phagocytic cells of the bovine mammary gland are PMN and macrophages. In the normal mammary gland macrophages are the predominate cells which act as sentinels to invading mastitis causing pathogens. Migration of neutrophils into mammary tissue provides the first immunological line of defense against bacteria that penetrate the physical barrier of the teat canal. Specific ligands on the PMN surface are required for directed migration and phagocytosis. In response to infection, freshly migrated leukocytes express greater numbers of cell surface receptors for immunoglobulins and complement and are more phagocytic than their counterparts in blood. Phagocytic activity rapidly decreases with continued exposure to inhibitory factors such as milk fat globules and casein in mammary secretions. Advances in molecular biology are making available techniques, and products to study and modulate host-parasite interactions. The successful formation of bifunctional monoclonal antibodies for the targeted lysis of mastitis causing bacteria represents a new line of therapeutics for the control of mastitis in dairy cows.