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Skip to 0 minutes and 13 seconds In this short video, we’ll take a look at what happens to your body when you catch the flu. It’s winter. The weather is terrible. Christmas is just a memory and you’re on a crowded bus. Then somebody sneezes. From the nose and mouth comes a fine spray of mucus-laden droplets. So fine, in fact, that it may be invisible to the naked eye. That person is suffering from flu. Not so badly as to prevent them getting on the bus, but suffering nevertheless. The flu virus infected respiratory passages are secreting millions of newly produced influenza particles. The irritation caused by the breakdown of the surface mucous membranes in their nose, throat, and lungs induces a sneeze reflex.

Skip to 0 minutes and 56 seconds For the viruses this person is carrying, this is the first step on their way to a new host. But this is also a very dangerous time for the virus particles. Viruses prefer to be inside hosts where it’s warm and moist and their needs are provided for, not in the harsh outside world. But flu viruses are hardier than most. As the spray of droplets in the sneeze emerges from the nose of the sufferer, it aerosolises, meaning that the droplets are so small that they dry almost instantaneously on contact with the air. That would kill many viruses. But flu virus is resistant to this drying process.

Skip to 1 minute and 33 seconds The aerosol particles can be caught up in air currents and then travel across the bus, where they can be inhaled directly by other passengers. Or they can fall on to surfaces, for instance, seat rails and door handles. The next person touching that surface will have dried virus particles on their hands. Those hands only need go into a mouth, a nose, or an eye for the virus to enter its next host. The phrase “fomite transmission” is used to describe virus transmission via surfaces and objects in this way.

Skip to 2 minutes and 5 seconds The mechanics of virus attachment are a thriving research area in flu virology because of the realisation that one of the reasons why bird flu is not readily transmissible to humans is because it attaches poorly to ourselves. For instance, the most feared strain of bird flu, H5N1, which has caused some very severe cases in poultry farmers in poorer countries, can bind to the human lower respiratory tract to the lungs, but not the upper respiratory tract. The reason for this is the preferred binding site of H5N1, which is a cell surface sugar based entity called Alpha-2, 3-sialylglycan, is only found in sufficient abundance in the lungs.

Skip to 2 minutes and 46 seconds If the H5N1 virus can reach the deeper parts of the respiratory tract, it can cause a very severe infection. But crucially, most viruses don’t get that far. And that’s why H5N1 in humans is virtually confined to poultry farmers in poorer countries who have prolonged contact with their birds under conditions of poor hygiene. By contrast, the preferred binding site of human flu strains, a variant called Alpha-2, 6-sialylglycan, is found in the human upper respiratory tract. So any human flu virus entering the body can bind much sooner and with a greater chance of success. We’ve now reached the stage that the virus you inhaled has stuck to the Alpha-2, 6-sialylglycan in your nasal passages and throat.

Skip to 3 minutes and 33 seconds The cell membrane then engulfs the virus in a little pocket called a vesicle using a process called endocytosis. The vesicle is then transported deeper into the cell by the cell’s own structural components, the first of many instances of normal cellular processes being subverted and hijacked for the benefit of the virus. Soon, the virus undergoes uncoating and the protein and genome components are released into the cell. The genome segments, stabilised in complexes with the viral nuclear protein, find their way to the nucleus, where the cell’s genome is located. Again, with the aid of host cell functions. Once inside the nucleus, the virus protein polymerase complex sets to work making copies of the virus genome segments.

Skip to 4 minutes and 18 seconds Some of these will end up in new virus particles. Others will leave the nucleus the way they entered back into the main outer part of the cell, the cytoplasm, where host cell machinery is again subverted to make viral proteins, some of which return to the nucleus to combine with the newly produced copies of the virus genome. It wouldn’t be excessive to suggest that the cell is now effectively working on behalf of the virus rather than for your own benefit. Everything eventually comes together again in the cytoplasm, where the virus particles are reassembled. The neuraminidase protein then coordinates the budding process. This is like a reversal of the previous uncoating.

Skip to 4 minutes and 58 seconds The new viruses are wrapped in parts of the host cell envelope, which then separate off from the host cell with their haemagglutinin and neuraminidase proteins protruding from the surface and all the other viral proteins inside, along with the new viral genome segments. So we’re now back where we started. And one viral life cycle is complete. The difference is that the number of virus particles in your body has now been vastly amplified. And each of these will find a neighbouring cell and start the same process all over again. If your body doesn’t start to do something soon, it will be overwhelmed. The human body fortunately has various defences against viruses and similar invaders.

Skip to 5 minutes and 40 seconds These are generally classified into two groups, innate and adaptive defences. Innate defences, defined in this way, are simply those that don’t involve a host antibody response. For instance, let’s take the example of simple barriers against infection. The airway passages are coated with mucus, which can impede the virus’ access to the host cell. Another aspect of the innate immune response is a familiar thing called inflammation. That redness, the swelling and pain that’s common to so many illnesses and injuries. The inflammatory response recognises signs that not all is well in the body. For instance, the presence of bits of damaged cells which could indicate that viruses have already begun their work. It’s all quite complicated.

Skip to 6 minutes and 25 seconds But the main thing to remember is that the innate immune system is a one size fits all response. Different viruses may trigger the innate response in slightly different ways and to different degrees. But the response does not pay much attention, if any, to what virus is infecting us. On the other hand, the acquired or adaptive immune response is specifically tailored to whatever viral or other infectious disease threat we’re facing. This made to measure response is due to antibodies, proteins which directly recognise and bind to viral proteins, deactivating them and targeting them for destruction by other parts of the immune system. However, this won’t happen instantly. It takes some days for the adaptive immune response to get going.

Skip to 7 minutes and 14 seconds However, once it is underway, the job doesn’t end once you’ve defeated your current virus infection. The antibodies produced will remain circulating in your body and will prevent reinfection with the same virus. By now, you’ll be feeling really unwell. You know that you’ve got the flu. The innate immune response has got inflammatory signalling molecules coursing through your system. Your head is aching, your throat is sore. You’re beginning to shiver and finding it difficult not to keep coughing and sneezing. Much of this, though, is for your own good. The virus is also starting to find life a little more difficult inside the host that has just turned nasty.

Skip to 7 minutes and 52 seconds However, just as we’ve evolved our innate immune response to make life unpleasant for viruses, the viruses have evolved to take advantage of that for their own purposes. The sneezing that’s a product of your inflamed nose and throat is also, as we’ve seen, the virus’ exit route out of you and into another host. What happens next is of crucial importance and determines if you’re one of the vast majority that live or one of the unlucky few that die. The innate response will be at its height, and you may now be aching all over, feverish, devoid of all appetite and barely able to move. But your adaptive immune response, your antibodies, is starting to come through.

Skip to 8 minutes and 34 seconds Flu proteins will be recognised, bound, and destroyed. Gradually, the number of virus particles in your system will start to decline. Antibodies are the real heavy artillery of the immune system. And provided you can generate enough of them with a good enough match to the strain of virus you’re suffering from, you will soon clear the virus and also in the process cease to be infectious to those around you. So well done. You are now better. The speed of your antibody response may be aided by prior vaccination. For instance, the antibodies produced in reaction to your flu jab will be lying in wait for the virus. And your adaptive immune response may be so rapid that you scarcely realise you’re ill.

Skip to 9 minutes and 15 seconds But what if things don’t go so well? Many people have immune systems that are sub optimal. For instance, very young children, very old adults, people with immune dysfunction, transplant patients on immunosuppressive drugs, or people with AIDS. For these people, a failure to stop flu in time may mean serious damage to the lungs starts to occur. So then pneumonia can set in. And also secondary infections. Bacteria and other viruses can then start colonising the airways. Nevertheless, secondary infections can be the final straw for a body battered by a serious influenza attack. The prolonged nature of the illness can be a problem, too. Since you aren’t feeling like eating and drinking, you may become dehydrated.

Skip to 10 minutes and 0 seconds And after your lungs, the next vulnerable organ system is your kidneys. Under these circumstances, the innate immune system’s inflammatory response can start to become a little desperate and even disorganised. A syndrome called cytokine storm can set in. And this may lead to total organ failure, including internal bleeding. But it was reported extensively in the flu pandemic of 1918. If you have reached that stage, there’s very little that can be done for you.

The Life Cycle of Influenza

Watch this video which traces the course of an influenza infection, from the moment when it enters your body, to your ultimate recovery or death.

Try to recall the experience of an attack of influenza and how you felt at each stage. Think about how those symptoms relate to the events described in this video.

A lot of the symptoms of influenza are not due to the virus itself, but to the response mounted by your immune system. This response has two wings: the innate, which is a general response to infection and which is activated very soon by the early signs of viral infection, and the acquired, which is a specific response involving antibodies and which takes a while to develop.

The acquired immune response is the basis of vaccination. The first exposure to a virus that you receive when you are injected with a vaccine, allows the formation of antibodies against that virus. This first acquired immunity can take a while to develop, just as would happen when you are exposed to any virus you’ve never encountered before. However, once this is established, there will always be a few immune cells circulating in your bloodstream that can produce those antibodies.

On your second encounter, and subsequent encounters, with the virus those cells can rapidly amplify their production of antibody, neutralising the virus perhaps even before any symptoms appear at all.

Links to some further reading are provided below.

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This video is from the free online course:

Influenza: How the Flu Spreads and Evolves

Lancaster University