[SOUND] [MUSIC] So we've spoken so much about infectious disease and it's impact on production systems, and as we consider the pathogen's side, the microbe side of infectious disease would be remiss to not think about the host side. You see, when we adopt certain management practices, and we try and reduce disease, a lot of our practices are aimed at shutting down the pathogen or killing the pathogen. But in some ways a better way is to make the hosts themselves more resistant to disease. So to understand how we do that, we have to know the workings of the immune system. The immune system is that part of the body, that body system which interacts directly with microbes. Whether they be bacteria, viruses, or parasites, endoparasites and ectoparasites. Our immune system is what prevents those microbes becoming established and causing disease. What I want to do is really give you a big overview and relate a little bit to what's taking place inside the animal and what kind of signs you might see at different stages of the immune response or particularly the inflammatory response, the first response that a host will have against an invader. Because if you understand that, then you can institute early detection systems that the immune system, the inflammatory response is in place. And that animal is in the midst of fighting an invader. So the first thing the immune system does is recognize danger. Really a pathogen becoming established or the presence of a toxic component from a pathogen that enters the host. For the host to produce any response to it, it has to recognize that it's dangerous. On cell surfaces around the body at strategic sites there a specific receptors on the cell surfaces called pathogen recognition receptors or PRRs. Those PRRs are designed to recognize specific signals from the pathogens called PAMPs or pathogen associated molecular patterns. So as soon as those PAMPs engage the PRRs or those receptors that is the signal for danger, that then starts a whole series of processes, in fact a cascade of processes by which the immune system is up regulated to defend against the organism that danger signal has alerted the immune system to. And the immune system also responds to other foreign, or threatening events such as trauma, such as a damage to a cell, and they, when a cell is damaged, they release certain elements called DAMPs, and that is another, it's a danger signal which the immune system can recognize. So the first stage in the immune response, is recognition of a danger signal. So after that danger signal has been recognized, the first response of the body is to try and neutralize that danger signal or the organism that is expressing that danger signal. So that can occur by a whole set of different mediators. There can be cells, or there can be chemicals that are secreted at the site which the pathogen exists. Some of these are called a proteins, they're called antimicrobial peptides. So as soon as the danger signal's been recognized, for instance, in the nasal cavity or at a mucosal surface, that part of the body, those lining cells will produce an anti-microbial peptide. A peptide which has the ability to eat and neutralize that agent or even destroy it. So after recognition of the danger, the second stage is to try neutralized the danger. So, the third stage of the inflammatory response is a signalling activity. So, with most immune responses, most inflammatory responses, those first two events will have neutralized the infection to a certain site. But, the body is also signaling to a broader immune response that actually the danger is there. So this signaling response occurs by the expression of surface molecules at the inflamed site. So, by recognition of the danger signal, the cells that carry those recognition receptors will then start to express molecules, which tell other immune cells that that is the site in which infection is taking place. Now, the body at this stage is trying to localize the infection. What the body doesn't want is for those infections to become established systemically to reach other parts of the body. So the recognition, and the neutralization, and the signaling in an attempt to bring other active elements of the immune system to that site in the anticipation, in the hope of localizing because a localized infection is much less damaging and has much less ramifications than a systemic infection. The fourth element of this immune response or inflammatory response is actually recruitment. This is really an amplification stage, this is saying that all of those local factors aren't enough to protect the body against this invading organism. Either the organism is particularly strong and has certain virulent factors, factors which make it a very dangerous organism or the number of infectious agents are too great for those local mechanisms to neutralize it. So this is a stage of amplification. And this occurs by recruiting other parts of the immune system. The immune system isn't just localized but all the time there are immune elements circulating around the body in the blood system, at mucosal surfaces, there's constant passage of sensitized immune factors moving around the body. And they are, at any one time, able to exit that circulation system and accumulate at a site of infection or inflammation. So, these will recognize the signalling process. The cells that are close to that damaged area, or the area in which is being infected, they will express certain receptors. The cells that are scanning that area will recognize those receptors, and they will exit the bloodstream at that site, and accumulate there. There are also, the release of a number of soluble mediators at that site as well. And the net result of that is to increase the blood supply. And this is now giving us some of the clinical signs that we'll be able to recognize. If you think about it now the immune system, instead of being neutralized at one site, is beginning to signal that it's damaged and recruit other cells. To do that it needs more blood cells, more blood, and more blood cells. So what would that look like? That might look like, imagine if an animal or you had cut your skin or had an infected skin, you'll start to see swelling of that site, or redness of that site. Two of the main signs and early signs of the inflammation. That's telling at what stage is taking place. Neutralization hasn't been affected. We're now amplifying recruiting other soluble and cellular agents to that site to try and combat that infection. So the next stage of the inflammatory response will be destruction of those bacterial agents, or those viral agents, or those invading organisms. So that takes place because now we've recruited all kinds of cell types and all kinds of soluble mediators. Some of those cells are called neutrophils, so they particularly have an activity in which they can engulf invaders. They can eat them. They're called phagocytes. They can take them into their cell cytoplasm and engulf and ingest them. So, they're some of the first cells that are at those sites. And there might be other soluble mediators, certain proteins. That's also effective at destroying bacteria, rupturing their cell wall, neutralizing viruses, aggregating them together so that the phagocytes can eat more vermining, engulf them more easily. So now, the blood system and the immune system is looking at destroying, and not just destroying, but removing those agents as well, because there's also a circulatory system which collects all of that debris and removes them from the body. So the immune system isn't just aimed at killing pathogens. It's also aimed at removing them as well, and the body has all different sites which are able to processed damaged cells and cells which have collected microbial or pathogenic agents. That occurs at the lymph nodes, that occurs in the liver, that occurs in the spleen. So, all of these are sites in which those bacteria can be finally dealt with and digested and taken away so they cause no more damage to the body. But the last stage of this inflammatory process that deals with most infectious agents is healing. So the immune system is really a homeostatic process. The point of the immune system isn't to kill microbes, it's actually to restore health, it restores normality. So once that foreign agent has been recognized, once the neutralization process has taken place the amplification steps and the recruitment of other cells, the destructive processes, and the removal of those agents has taken place. The cells that are left, or the damage that's been incurred needs to be healed, and so the last part of this inflammatory response is to recruit cells and to recruit soluble mediators. That'll restore health to that damaged part of the body. So healing is part of the inflammatory response. And what we're looking about when we have an animal with a robust immune system, we expect when it's exposed to an infectious agent that it will heal within a certain period of time. Within that period of time, if its immune system is working and the infection hasn't won the battle, then you'll see healing. That redness, that swelling will go away. The pain associated with it will disappear. And that should occur within 48 to 72 hours. If you have an inflammatory response that goes beyond that, that shows you that the immune system is now recruiting additional defenders, as it were, the adaptive immune response. And that's when other interventions are needed. But by far, most infections are dealt by those seven stages of the inflammatory response, and that's what you'll be looking for you in your animals. [MUSIC]
