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Current time:0:00Total duration:9:09

Video transcript

so we've learned the pertussis is caused by a contagious bacterial infection that causes damage to the upper respiratory tract so in this picture the infection would be here in the main airway leading to the lungs and this airway is called the trachea the bacteria that damages this airway during an infection is called Bordetella pertussis and would sort of look like this if we were to look at under a microscope it gets its name Bordetella from the man who first isolated the bacteria and pertussis is Latin for a thorough cough so the Specht area is appropriately named because the main clinical symptom of pertussis infection are horribly violent coughing fits and these fits are frequently followed by a whooping noise when breathing in which is how the disease gets its second name whooping cough but to explain how pertussis infects the body and causes the symptoms associated with the infection we should take a closer look at this section of the lung and start with talking about what a normal healthy immune response to bacterial infection would look like normally bacteria will be kept from entering the body by a barrier of cells between the airway and the rest of the body that would be underneath these cells and there are different types of barrier cells which perform lots of different functions but I'm going to highlight only two in particular because they're really important in their role of the pathophysiology of pertussis one are these cells with these really long hairs that project into the airway the long hairs are actually called cilia and their purpose is to sweep out mucus there anything foreign to the body that we might breathe in the mucus which I'm drawing here in pink is made by these neighboring cells and the mucus is secreted into the airway to keep the airways moist and help trap foreign material making it easier to remove but no matter what special functions these barrier cells might have they all have the ability to sense bacteria in the airways either by binding to the bacteria directly or binding to something the bacteria secreting and when the cells detect that there's bacteria they send out chemical signals almost like an SOS signal to recruit immune cells to the site of infection to help fight it if it helps I like to think of this as the cells giving off a signal similar to how a police officer seeing a criminal would send out a call for backup to help catch the criminal and then in this lung tissue here are immune cells called macrophages necro phage macrophages are often the first to detect an infection after the barrier cells and they detect the bacteria in a similar way as the barrier cells and they send out an SOS signal but they also do something special they swallow the bacteria so let me draw some bacteria here and the macrophage actually wraps itself around the bacteria until it's completely surrounded and inside the macrophage in this little sac once it's in the cell a few other sacs containing chemicals and proteins showing the bacteria sac and kill the bacteria and this is how a body kills and clears and infection but this can be a big job so the immune system has additional cells that can help the macrophage when the SOS signal goes out another cell called a neutrophil follows the signals and it comes to help swallow up the bacteria neutrophils are usually circulating in the blood so let me draw a blood vessel here in the lung tissue and here's a neutrophil circulating through it but when an SOS signal goes out the blood vessels and the infected tissue become leaky so I mean the blood vessels had now have these tiny little gaps in them that the neutrophil can squeeze through and into this issue also responding to the SOS signal is another immune cell in the tissue here called a dendritic cell dendritic cell it responds by swallowing a sample of the bacteria or proteins it's secreting it leaves the tissue and travels through the vessels to lymph nodes which I'm going to draw here in green now lymph nodes are very small oval shaped organs - located all over the body and the purpose of the lymph node is to actually allow dendritic cells with their sample foreign material to interact with other immune cells that are important in producing antibodies against this foreign material anybodies are like tags that flow through the blood through the gaps in the blood vessels that we just talked about and to the site of an infection there they very specifically stick onto the invading material and market for destruction by calling over the swallowing cells antibodies are so important because they make the process of finding and swallowing material more efficient so pertussis bacteria makes lots of proteins which allow it to efficiently infect the body and then avoid being detected and killed by interrupting the normal immune response as much as possible first the bacteria avoids being removed from the airway by the ciliated cells by anchoring onto them and that's what I'm showing here with this yellow protein on the surface of the bacteria anchoring into the ciliated cell it's an important step because without efficiently anchoring to the airway pertussis would be swept out of the lungs and it would not have a chance to infect the body at all in fact this step is so important that two different proteins on the surface of the bacteria are used to secure it to the ciliated cells and these proteins are called pertactin and filamentous heme agglutinin once it's anchored it can begin to multiply and release proteins that are called toxins a toxin is poisonous to the cells it infects and it can cause cellular dysfunction and death here tracheal saito toxin kills the ciliated cells and as several ciliated cells die the mucus in the airway begins to build because the cilia isn't there to sweep it out of the airways and as the mucus builds it triggers a coffee flecks resulting in the forceful coughing fits that pertussis is known for now why pertussis kills the very cells that it needs to stay anchored in the airway is definitely confusing but it's a way for pertussis to get into the underlying tissue and also a way to directly deliver additional toxins to the body so yes pertussis is going to release even more toxins and they are pertussis toxin which I'll abbreviate PT and adenylate cyclase toxin and I'll abbreviate this AC T these toxins cause impressive dysfunction to the immune system and they have a way to interfere with the normal immune response at nearly every step of the process and while they have similar effects on the immune system they work at different distances so I mean a CT has an effect mostly on the cells in the tissue immediately nearby the pertussis bacteria but PT can travel further away from the bacteria and still be active and when PT or a CT reaches L they travel inside and they disrupt the normal functions of the cell so for the barrier cells and the macrophages PT and AC T prevent them from sending out this SOS signal to notify the rest of the immune system that the infections occurred and if there's no SOS signal you can imagine that neutrophils aren't going to be able to follow the signal to travel out of the blood and into the tissue where the infection is happening and over here the gender it excels won't be able to head to the lymph nodes this is particularly bad because remember that this is the initial step that will eventually lead to the production of antibodies when the antibodies are key for removing this infection quickly and effectively but even though the macrophages and the neutrophils do succeed in swallowing up some of the infectious material the toxins actually prevent the fusion of the bacterial sac with the chemical of protein sex inside the cell so the bacteria actually is never killed but that's not all the toxins do remember back to when I was talking about the neutrophils and antibodies coming from the blood into the lung tissue through these gaps in the blood vessels these holes are important in allowing a full immune response but having too many holes is also a problem and this is something that happens with PT and AC T it's a problem because fluid from blood vessels leak out from these holes into the tissue and start to fill up the tissue so the tissue swells think of this almost like a sponge swelling when it takes up water swelling the tissue can make it difficult to breathe because the tissue pushes into the airway and causes them to narrow this narrowing causes air resistance when rapidly trying to draw in air after a coughing fit and contributes to the classical whooping noise that the disease is known for and since PT can work at long distances from the bacteria it has an interesting effect on the body system-wide particularly on the lymphocytes now the Linda sites are the immune cells that I was talking about that were responsible for the production of antibodies and PT acts as a growth factor and that is that when it's sensed by the lymphocytes it causes them to divide rapidly and multiply to unusually high levels this is called lymphocytosis and it's most noticeable clinically in infants with pertussis where high levels can increase to almost three times the normal levels of lymphocytes found in the blood the reason this happens isn't really clear but the increase in the level does reflect the extent and the severity of the infection so now the proteins and the toxins that I just mentioned aren't the only ones that the pertussis bacteria mix but have decided to focus on them specifically because they're commonly used as important components of the vaccine against pertussis