Coordinating your defences

So you’re trekking through the rainforest in the Danum Valley trying to find the elusive orang utans and you slip twisting your ankle. As you fall you reach out and grab a vine which leaves you with several deep splinters from the thorns. Your friend, who has been feeling unwell ever since the flight to Malaysia, rushes over to help you up and in the process coughs in your face spreading the influenza virus that she has to you.

Your body is now dealing with three different injuries/diseases and I shall discuss the role of the specific and non-specific immune system as it fights to get you healthy again.

I’ll start with the injury to the ankle. Your ankle is injured and is not responding to a pathogen therefore all responses to this injury come from your non-specific defences. What you have done is stretch and stress the ligaments that connect the bones in your foot. In response to tissue damage and damage to blood vessels mast cells and platelets release histamine. The platelets work to repair any damaged blood vessels however the histamine has caused these vessels to dilate and become permeable. More blood is transported to the area and fluid moves into the interstitial fluid around the injury bringing many of the body’s white blood cells with it. These leukocytes run around looking for pathogens, often releasing more histamine as a result. At the same time the damaged capillaries are leaking blood into the interstitial fluid that will result in a bruise. The damage to the blood vessels causes a class of hormones, endothelins, to be released that act as vascular constrictors narrowing the damaged vessels to limit blood flow. These hormones work in antagonism to histamine, histamine causing the dilation in non-damaged vessels. The blood that has leaked into the interstitial fluid is gradually broken down by phagocytosis and this causes the changes in bruise colour over days.

So you are left with a sore, swollen, hot, bruised ankle as your body begins to repair the damaged tissues.

The splinters in your hand have allowed foreign particles to enter your body. Some of the splinters unfortunately had some dodgy bacteria on them. As the thorns pierced your skin they breach the skin barrier. In response, platelets begin the blood clotting around the site of the wound and release histamine. Mast cells, also present, release histamine and now the inflammatory response is triggered, the capillaries dilate, become permeable and neutrophils arrive on the scene. These neutrophils begin the phagocytosis and chemical attack of both the splinter (relatively unsuccessfully) and the bacterial pathogens that were also introduced to the wound. Responding a little slower than the neutrophils, macrophages arrive and continue the digestion of the bad guys while releasing cytokines that attract more leukocytes to the area of infection.

After destroying around 100 bacterium each the macrophages die and become the wonderful stuff we refer to as pus.  But before they die the macrophages have done something else. They have taken MHC markers from the surface of the pathogens and placed them on their own cell membrane. This allows T helper cells, that have now arrived on the scene, to recognise the antigen and kick start a clonal response and release of specific antibodies in B cells. It takes a bit of time but the specific and non-specific defences have defeated the nasty bacteria, however, the splinter, now surrounded by interstitial fluid and pus, is sore. The pressure of the fluid around it, combined with a little squeezing from you, force the splinter from the wound site. Platelets respond to repair the wound again and hopefully, no further pathogens got in this time. If they did, the process starts again.

Now you’re sitting on your veranda with a sore foot and hand but you are starting to get better, however, by now your body is responding to the flu virus you inhaled. When your friend coughed at you many of the virus particles landed on your skin and face. As they didn’t reach the host tissues they didn’t infect you. It was the particles you breathed in that have caused the problem. Influenza virus, or the flu as I’m going to call it from now on, infects the epithelial cells of the respiratory tract (the surface cells). The mucus lining of the respiratory tract provides some form of protection as a barrier both physical and chemical. And in this mucus will lurk IgA B cells, ready to respond to known pathogens. Unfortunately for us, the flu mutates rapidly and regularly changing its external surface markers so it is not immediately recognised by our lymphocytes and further, the flu virus diffuses rapidly through this mucus to the epithelial cells beneath. Once it has reached the target cells, the flu, an RNA virus, injects its genetic instruction into the cell. Here it is integrated into the cell’s genetic instructions, hijacking the cells organelles causing them to make many, many copies of this virus. Eventually the cell will lyse spreading the virus to neighbouring cells and, via coughing and sneezing, to people around us. In response to the invading virus, the cells produce interferon and cytokines. This works to interrupt viral replication, ‘warn’ neighbouring cells and attract NK cells to the area. I’ve explained the role of NK cells earlier but in a nutshell they use a one-two chemical combo to force the infected cells to undergo apoptosis. While you get a fever when battling the flu, this is not a non-specific response, rather, fever as well as muscle aches, tiredness and general feelings of crappiness result from the effects of interferon.

The infected cell also fights back by placing viral antigens on its surface. Cytotoxic T cells recognise these foreign non-self antigens on the surface of a self cell and respond by producing proteins that punch holes in the infected cells membrane. While this doesn’t necessarily kill the virus, it interrupts its life cycle preventing further spread. By now, your body has begun to defeat the flu and is rapidly producing antibodies and creating memory cells for future infections. Your antibody defences are relatively limited in response to a new virus, however, it is very effective in response to future infection by the same virus.

So, your ankle, hand and respiratory system have healed themselves. Your body has responded with generic and specific defences, some chemical, some cellular, and it has added these new pathogens to its biological database for quick and efficient response next time. After a couple of days in bed, feeling a fair bit better you limp to the restaurant to finally get something to eat and hear everybody else’s tales of jungle encounters . Unfortunately, the cook didn’t wash his hands properly and the bacteria Salmonella sp has now entered your system and is starting to multiply in your gut...

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Disclaimer: The Danum Valley is a magical place and your chances of getting sick there are probably significantly less than in Melbourne. I have never been to a place before that has filled me with such awe. Pygmy elephants, orang utans, hornbills, so many types of primate and reptile... And the food is amazing and the cooks DO wash their hands! If you ever get the chance, visit. But bring leech socks.