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Article from www.ProgressiveDairy.com Ask a student about colostrum, and the response will be passive immunity. That’s correct, but it is only part of the story with respect to the biological activity of colostrum. Colostrum is the first milk produced by the mammary gland prior to parturition. This first milk is rich in immunoglobulins (proteins) as well as other chemical constituents and cells that impact the health of the newborn calf. At birth the calf is very susceptible to disease because in cattle there is little, if any, placental transfer of antibodies, in contrast to humans where placental transfer of antibodies from mother to fetus is high. The calf evolved with the ability to absorb intact immunoglobulins (protein antibodies) in the small intestine by a passive mechanism that allows the colostral antibodies to enter the blood and protect the calf from diseases prevalent within the herd. This mechanism is called passive transfer. These passively absorbed immunoglobulins (Ig) protect the calf as its own immune system matures and produces antibodies. Cornerstones for colostrum management include colostrum quality, colostrum volume, age of the calf and bacterial contamination. Everything we do with calf management is based on science, even though we might not think of it this way. Research in the mid-1990s estimated that 30 percent of the mortality events that occurred during the first three weeks of a calf’s life were attributed to failure of passive transfer of immunoglobulins. Most reports indicate that 40 percent to 60 percent of the calves that are allowed to suckle their dams to obtain colostrum fail to obtain passive transfer (adequate amount of Ig intake). Hand-feeding colostrum is the better method to ensure that passive transfer occurs, and the following comments are based on colostrum programs where colostrum is hand-fed. Immunoglobulin (Ig) concentration of colostrum is one indicator of colostrum quality. Immunoglobulin concentration in milk decreases dramatically by the second milking, and by the fourth milking, Ig concentration is at a concentration for typical milk. Colostrum quality can be measured by using a colostrometer that relates density to the higher Ig content of the first milk. There are also commercial kits available that will measure colostrum quality, for example providing an estimate of the concentration of immunoglobulin G (IgG); IgG is the Ig found in highest concentration in colostrum. Article from www.ProgressiveDairy.com Phoca PDF Article from www.ProgressiveDairy.com Visual appraisal including color, consistency or thickness is not a good measure of colostrum quality (Ig concentration). An on-farm program involving a colostrometer or commercial test kit is a good management program, even if these are used only occasionally to monitor colostrum quality. Large dairy farms often pool colostrum from cows with the goal that “on average” the colostrum quality will be acceptable for feeding. Pooling of colostrum from multiple animals will likely be an issue in the future, as transmissions of cells or pathogens affect the transmission of bovine leukemia virus (BLV), Johne’s and possibly other diseases. Colostrum volume, the amount fed, comes into play because most management programs on dairy farms involve feeding a set amount of colostrum (2 to 4 quarts per calf). Recommendations vary, but in general the goal is for the calf to consume 100 grams of immunoglobulins within six hours of birth. The issue of feeding 2 or 4 quarts should be based on science. If colostrum is tested and contains 60 mg Ig/mL, then 2 quarts provides an adequate amount of Ig in the first feeding based on the current state of the science. 2 quarts = 1.893 liters or 1,893 mL So (60 mg Ig/mL) * (1,893 mL) = 113,562 mg or 113 g Ig intake – which is adequate. Then why 4 quarts? This comes from an article in Hoard’s Dairyman, March 25, 1994. The authors of the article discussed the IgG1 concentration in colostrum across 919 cows. If colostrum for all cows was used, the average IgG1 concentration was 35 mg/mL. To provide 100 g IgG1 to the calf, it was necessary under that scenario to feed 3 quarts of colostrum. So does it make a difference if you feed 2 or 4 quarts? Probably not, as long as you are feeding very good to excellent quality colostrum. It is likely that 2 quarts within the first few hours after birth are adequate based on the research to date. If your colostrum quality is not tested frequently, then maybe 4 quarts is the better choice to ensure adequate Ig intake. But we cannot forget the science side. The calf did not evolve to consume large volumes of colostrum immediately after birth. The abomasum was designed as the gastric (acidic) compartment of the ruminant stomach. The pH is between 1 to 2 – very acidic. This acidic environment is bactericidal, which kills many harmful pathogens that enter the gastro-intestinal tract that might potentially colonize the small intestine and cause scours. Article from www.ProgressiveDairy.com Phoca PDF Article from www.ProgressiveDairy.com We may not want to overwhelm the ability of the abomasum to acidify digesta. Right now we do not know the impact of a volume of colostrum fed on the ability of the abomasum to control harmful pathogens. For age of the calf when colostrum is first fed, the sooner colostrum is fed, the better. Ideally, colostrum should be fed within six hours of birth. Research has shown there is a decrease in absorption rate of Ig with time after birth. There is a narrow window of time when the small intestine of the calf will absorb whole proteins (Ig). Eventually, the intestine goes through a process referred to as gut closure, a process where the cells lining the small intestine and their tight junctions no longer have the ability to absorb whole proteins. Gut closure occurs spontaneously sometime between 12 to 24 hours after birth. Gut closure is a natural protection mechanism because the gastro-intestinal tract is one of the most accessible routes for pathogens to enter the body. If whole proteins can pass the gut barrier and enter the bloodstream of the newborn calf, so can pathogens including E. coli and salmonella. Feeding colostrum within six hours of birth enhances gut closure. Research showed that feeding colostrum at four hours after birth resulted in gut closure for IgG occurring at 25-hours-old. In contrast, if the first feeding of colostrum occurred at 12 hours after birth, gut closure occurred later at 30-hours-old. We still do not understand the processes involved with gut closure, but once this event occurs the absorption of Ig stops. Once gut closure is complete, Ig are digested to their component parts, amino acids, that are absorbed from the small intestine. So the sooner colostrum is fed, the better for calf health. Bacterial quality of colostrum is a cornerstone that has only recently been considered. Colostrum stored at room temperature for any period of time can result in bacterial growth. Research at UC Davis by Jim Cullor showed that bacterial numbers in colostrum can exceed 10 million colony forming units/mL of colostrum. A study in 2002 that surveyed commercial dairy farms reported that 82 percent of the colostrum samples exceeded 100,000 colony forming units/mL of colostrum. Feeding colostrum with a high concentration of pathogens is setting the calf up for scours. If whole proteins (Ig) can be absorbed into the blood during the first few hours after birth, so can pathogenic bacteria. There are producers who are pasteurizing colostrum to minimize the bacteria in Article from www.ProgressiveDairy.com Phoca PDF Article from www.ProgressiveDairy.com colostrum. The pros and cons of pasteurization when it comes to colostrum are still under investigation. It might sound simple, but it is not. Heat denatures proteins. There are reports suggesting that temperatures above 60ºC might denature whey proteins (the Ig fraction of colostrum). Temperatures above 65ºC also cause gel formation problems in the pasteurizer with colostrum, which plugs the system. What are we doing with high temperature and Ig? This is where science will step in and help to provide answers. So why is colostrum more than just passive transfer? Thus far, we have discussed passive immunity associated with the intake of Ig by the newborn calf. These Ig are absorbed intact from the intestinal tract, where they then enter the systemic circulation to provide antibodies against pathogens that can cause disease until the calf’s own immune system develops. In addition to the colostral Ig that are absorbed, there are also colostral leukocytes than can be absorbed. Plus, colostrum also provides a local effect; an effect related to impacts within the intestinal tract. It was recently discovered that colostrum contains maternal leukocytes, although we do not know the importance to the calf. These leukocytes consist of macrophages, lymphocytes (B cells, T cells, and natural killer cells) and neutrophils. Research in 2005 demonstrated that ingestion of these maternal leukocytes in colostrum by the calf stimulated the calf’s immune system. The response is complicated in that these leukocytes from the cow were potentially involved in the development of the antigen-presenting capacity in the calf. Calves fed whole colostrum developed these antigen-presenting cells (APC) more quickly than calves fed cell-free colostrum (no leukocytes). These APC cells have receptors that stimulate T cells. Basically, these receptors on the APC cells serve as an alarm component of the immune system to let other immune cells (for example, the T cells) know that there is an invader present. The T cells are lymphocytes, and there are a number of different T cells (helper T cells, killer T cells) that assist the immune system to attack an invader to the calf’s systemic circulation. The question is: What are we doing to these maternal leukocytes when we freeze or pasteurize colostrum? Do these practices of freezing or pasteurizing colostrum affect calf health? There are numerous compounds in colostrum, for example peptides and oligosaccharides, that in addition to Ig may play a role in preventing pathogenic bacteria from colonizing the small intestine surface either through competition for Article from www.ProgressiveDairy.com Phoca PDF Article from www.ProgressiveDairy.com receptors on the intestinal villi of the small intestine or direct antimicrobial properties. There are many bacteria that enter the gastro-intestinal tract via the mouth. Most of these bacteria are non-pathogenic; they are swept out of the intestine and into the feces by the normal contractions (peristaltic waves) of the intestines. However, the pathogenic bacteria have unique characteristics that allow them to attach to the intestine cells. For example, some bacteria (for example enterotoxigenic E. coli) have pili or frimbria that allow them to attach to the intestinal cells and overcome the natural cleansing action of the peristaltic waves. These enterotoxigenic E. coli can cause scours. Research demonstrated that when newborn calves were not fed colostrum and were fed a solution containing E. coli, the E. coli were observed adhering to the intestinal epithelium. However, when colostrum was fed either prior to or after the feeding of the E. coli solution, bacteria were not observed to adhere to the intestinal lining. In addition, various compounds that have antimicrobial properties are found in colostrums, including lactoferrin, defensins and lysozyme. Colostrum has a local effect within the intestine. The local effect of colostrum can be enhanced. There are commercial products used to vaccinate dry cows, with the goal of increasing the Ig (antibodies) in colostrum to protect the calf. For example, dry cows are vaccinated for the K-99 E. coli pilus antigen, with the goal of increasing the minor components in colostrum that bind this bacterial pilus and prevent the bacteria from adhering to the intestinal lining. Oligosaccharides are sugars found in milk. Oligosaccharides are 3 to 10 sugar (monosaccharide units), in contrast to milk sugar, lactose, which is a disaccharide consisting of two monosaccharides – glucose and galactose. Oligosaccharides are low in cow’s milk, but oligosaccharides are the third-highest component in human milk behind fat and lactose. These sugar residues in human breast milk are reported to be one reason why breast-fed babies are healthier than formula-fed babies. These oligosaccharides in human breast milk bind pathogenic bacteria and prevent them from colonizing the intestinal tract of the newborn infant while consuming breast milk. The cow’s colostrum is higher in oligosaccharides compared with normal milk. Do oligosaccharides act the same way in calves? We do not know. One thing we do Article from www.ProgressiveDairy.com Phoca PDF Article from www.ProgressiveDairy.com know is that there are minor chemical components in milk that have local effects in the intestine – prevent pathogenic bacteria from binding the intestinal tract or have direct antimicrobial properties. That is why feeding colostrum two, three or more days following birth has a beneficial effect. The calf can no longer absorb the Ig, so it is not passive immunity. It is the local effect of these compounds, many still unknown, that prevent the pathogenic bacteria from colonizing the intestinal tract and maintain the health of the calf. Research continues in this area to advance our basic understanding. The future will be to enhance these natural protective mechanisms to maintain calf health and reduce the need for antibiotics. There is much more to learn about the biological role of components in colostrum. Feeding high-quality colostrum within six hours of birth is the most critical management practice conducted on a dairy to support calf health, but feeding colostrum a few days even after gut closure likely improves enteric health through local effects. So when you think about colostrum, remember it is more than just “4 quarts and done.” PD Ed DePeters Department of Animal Science University of California – Davis [email protected] Article from www.ProgressiveDairy.com Phoca PDF