Sarah Mikesell, editor with The Pig Site, spoke to Greg Page, global swine research manager with Trouw Nutrition, about immunity and the factors affecting the immune system development in piglets. Greg has spent the first 17 years of his career in poultry and fish nutrition and in the last three years has made the switch to leading Trouw’s global swine research team, which includes six researchers and 5 technicians who focus on executing the swine research portfolio at Trouw’s Swine Research Center in The Netherlands.
The global pandemic has made the whole world acutely aware of the importance of immunity and what a significant role it plays in maintaining human and animal health. But what do we really mean when we talk about immunity?
“Immunology is its own scientific discipline with its own language and terminology,” said Page. “When we talk about immunity, we're really talking about two things: the innate immune system and the adaptive immune system.”
Innate immune system
The innate immune system is the most basic system of protection that animals and humans have, and it includes things that are physical barriers to infection - skin, mucous membranes, saliva and tears. In the digestive tract, it also involves less specific approaches to disease prevention, like digestive enzymes and acids that are secreted during the digestive process. It also has physical responses such as peristalsis, which is the movement of gut tissue that moves food throughout the digestive tract. This is not unlike what humans experience when they have the flu – diarrhea is the body’s reaction to flush out the pathogens.
Inflammation is another well-established mechanism that is an example of a non-specific innate response. White blood cells are cells within the immune system that monitor tissue damage and secrete inflammatory mediators that signal other cells to aggregate to the site of infection. They then cause a cascade of reactions, which result in the swelling and the redness that’s often associated with inflammation. Signal molecules, like histamines are produced when people have allergies and can trigger a local inflammatory reaction, where they attract other cells that release compounds called cytokines that are signaling molecules that help regulate the development of other immune cells (examples include tumor necrosis factor alpha, interleukins and interferons).
Adaptive immune system
“We're really just scratching the surface of some of the compounds that have an impact on the immune system,” he said. “So far we’ve talked about the initial phase of the reaction of the innate system, but when we're talking about immunity, most people think of the adaptive immune system or acquired immunity, which is the process involving the production of antibodies.”
The adaptive immune response includes developing antibodies against an antigen, which is the protein molecule or compound in viruses or bacteria that white blood cells recognize and begin to form specific proteins against (antibodies). Those antibodies, at the right levels, help prevent further damage from the pathogen.
“When we're talking about adaptive immunity, we're talking about vaccines,” he said. “A naive host which is the pig in this case, is not protected against any particular pathogen until it's been exposed multiple times. There's a key reason why it's difficult to protect against the invading pathogens is that there is limited defense to avoid some of these diseases on the first exposure without a well-functioning innate immune system. It’s only when the innate immune system fails that the adaptive immunity becomes much more important and relevant. The challenge with the adaptive immune system is that it’s very highly specific, targeting very specific proteins from a single strain of virus or bacteria, which is when the pig can develop memory B cells and T cells that can mount a rapid reaction to prevent severe disease from recurring.”
However, the full response only occurs with the B and T cells after the host has been exposed more than one time. The first time they can't mount a memory response because they've never seen it before. This is one of the reasons why there are such challenges with the adaptive system or using vaccines is that the adaptive system takes time to build a response. It can take at least four to seven days in humans and similar timeframe in pigs, which is time lost from a production point of view for the animals. In some instances, boosters are also needed to mount an effective immune response.
The adaptive immune response is very relevant for piglets, as one of the components is the production of immunoglobulins, which are the antibodies that the sow can transfer to the piglets during the farrowing process via colostrum intake post-farrowing.
“It’s why colostrum intake is so critically important in newborn piglets. Through research, we have established that piglets need at least 250 grams of colostrum as a minimum threshold to ensure good performance,” he said. “It’s one of the key reasons why the adaptive system is important, not just for the piglets themselves and developing that response, but also for passive immunity which is transferred from the sow. It's a complex challenge and it’s why these two systems interact in very complex ways to help suppress and/or enhance each other. It’s a very active area of research currently in both human and veterinary research, particularly in swine.”
Four factors affecting the immune system development in pigs
Age of the animal
Age influences the development of the acquired immune system versus the passive immune system or what the piglet gets from the sow via colostrum and milk. Passive immunity can protect somewhat but only so far as to the pathogens to which the sow has been exposed and provided antibodies and immunoglobulins to the piglet. This benefit is transient, which means that the benefit subsides with time.
“The piglet receives very good early protection, but as the piglet develops, the protection level actually declines, and the passive immunity provided from the sow almost completely disappears by four to six weeks after birth,” Page explained. “It creates a window of opportunity where the adaptive system takes time to become active. The development of the adaptive system only starts developing after about three to four weeks of age. This is what we call the immunity gap between three to eight weeks of age, where the piglet is immune compromised and highly susceptible to disease pressure.”
Nutrition can play an important role in supporting a pig’s natural defenses through a variety of approaches. One example is the use of probiotics. These are bacteria that can modify the beneficial microflora that populate the intestinal tract and prevent pathogenic bacteria from colonizing in the digestive tract. Basically, they displace the negative bacteria with the positive bacteria. One of the challenges is that there are about 600 species of different bacteria that are known and can be cultured from the digestive tract. So, it’s difficult to define what a good microflora profile looks like.
“This is an active area of research where we are learning more as we go, and there are a number of probiotics on the market with varying degrees of efficacy that highlight the need for more research to improve the consistency of the effects of some of these technologies,” he noted. “Inconsistency can be due to a variety of reasons - some probiotics are more thermal stable than others through the pelleting process or a higher dose may be needed to colonize. Or the prebiotic components that we provide naturally through the diet are insufficient to ensure the growth of the probiotics. Inconsistency might also occur because the natural conditions are not right for the probiotics to produce the enzymes and antimicrobial peptides that help us to control pathogenic bacteria.”
Nutritionally, organic acids and essential oils and bioactive peptides can help control bacteria through antimicrobial properties, and some have also been documented to stimulate the immune system response beyond having beneficial effects on the structure of the intestinal tract.
“Creating tight junctions are another area where nutrition can help. We sometimes think of it as brick and mortar in the gut lining and if you don’t have mortar between the bricks, you have leaky cells,” he described. “This leads to translocation, where bacteria can go from the gut right into the bloodstream to cause systemic issues. We want to enhance those tight junctions and some of these nutritional products have properties that enhance those, but they also have another effect, which is increasing villa height or crypt depth which helps to improve nutrient absorption. They effectively increase the surface area for nutrient absorption. Those are a few examples, but there’s a whole host of bioactive products that are currently being researched that can strengthen not only the physical digestive tract but also enhance immunity and prevent a disease outbreak.”
Stress is a critical factor that researchers are just beginning to understand. As humans, we have experienced high levels of stress and understand that during this time we are more prone to disease. The same is true for piglets. The weaning process – when the piglets are separated from the sow to become an independent pig can cause emotional stress. At the same time, they are experiencing moving and handling stress as they are moved from the nursery into a completely different environment, including a new size pen and different climate. There will be new pen mates from perhaps different litters with different disease exposure.
“Plus, they will need to re-establish a new dominance hierarchy,” he noted. “The last piece, as if that weren't enough already, we're actually changing them from a liquid sow milk diet to a dry, complete feed, which will have a completely different nutritional profile.”
Pigs also experience the “fight or flight response” which is a stress response that can be manifested in the piglet through a number of different physiological responses, including increased heart rate, bronchodilation (rapid breathing), glycogenolysis, lipolysis, panting, decreased motility of the digestive system and increased adrenaline secretion and cortisol, which are stress hormones. These reactions have an overall impact on the physiology of the piglet. The ultimate consequence of these reactions is that the piglet is trying to overcome this stress and in doing so they divert energy or resources, whether that's energy, amino acids, minerals, etc., away from growing to maintenance in order to maintain homeostasis - body temperature, heart rate, etc. - and to mount an immune response.
“These end up having an impact which can manifest in many ways, but a key impact is reduced feed intake, which is why we see the growth check,” he said. “As an industry, particularly in post-weaning piglets, we are trying to find ways to mitigate the negative effects of this growth check, by looking at how to increase feed intake through palatability enhancers, mitigating stress, mitigating pathogens, etc. This is being done to try and enhance the piglet’s growth performance because we know the that heavier the piglet is at the end of the nursery phase, the better they grow in the grow-finish phase which means reduced days to market and better feed conversion. We want to set up the overall performance of the piglets for their entire growth cycle, by homing in on the first two or three weeks of life, which we call the LifeStart concept.”
Pathogen load is directly linked to the risk of specific diseases, which impacts of predisposition to disease. These are the indirect opportunistic diseases. Relating back to the immunity gap, a pig’s ability to respond to different pathogens is decreased right around the time when they're highly stressed. Thus, they have a limited amount of resources to mount a strong immune response. There may be a high level of pathogens in the nursery due to a farm’s specific issues in terms of sub-optimal hygiene processes like proper cleaning and disinfection, poor biosecurity, cross contamination, poor feed quality or using contaminated grains. All these issues can have a depressive effect on the immune system, creating a higher risk for disease exposure to piglets.
“We encourage very strong biosecurity and cleaning processes to ensure that we have a successful start post-weaning,” he said. “Producers need to look closely at what we call the interaction between feed-farm-health. Health is the immune response and what we can do nutritionally to enhance it, whether through the right balance of nutrients or gut health enhancing feed additives. Feed is about the nuts and bolts - ensuring you have high quality feed with a highly digestible balance of nutrients. Lastly is the health or the farm management aspect, which includes biosecurity, cleaning and disinfection procedures and environmental controls. Those three interactions combine to make a successful start for the piglets.”