The inflammatory response is crucial to protecting our body from injury and infection. The collaborative coordination of immune cells to specifically target and eliminate infection while also working to heal lacerations is essential to our survival. To understand the mechanisms behind inflammatory signaling, we must first address the clinical signs of an inflammatory response as well as how an inflammatory response is initiated.

Everyone has gotten an infection or cut at some point in their life. Having this experience means that you will already be familiar with some of the clinical manifestations of inflammation. These include: pain, redness, heat, and swelling. What many aren’t familiar with is that these clinical manifestations all serve to enable inflammatory cells to reach the infected and injured area. In other words, these uncomfortable symptoms are actually good! The feelings of pain you feel are from your body increasing your vascular diameter. This expansion of blood vessels increases the blood flow to the infected area, which results in pain. The redness and heat you experience are due to increased blood flow across the body, but especially near the major infection sites. The symptom of swelling is due to increased vascular permeability. This means that things, mainly fluid, from the blood can leave the blood supply contained in blood vessels and enter the surrounding tissue. Remember that all of these symptoms are due to your body modifying its current architecture to better enable inflammatory cells to reach the infected area. White blood cells (WBCs) are in the blood stream, so by increasing the blood supply to an area, you can increase the number of WBC reaching there faster. You also want WBCs to leave the capillaries to enter the tissues where the infection is. If the capillaries are sealed and not permeable, then this is not possible. Instead, you need to increase the permeability of the capillary wall to enable the WBCs to migrate out of the vessel. The most common clinical example of inflammation attenuation is with an infected nail. After biting your nail off, the subsequent infection goes away quickly because the innate immune system is really good at controlling and heightening the immune response to eliminate any infection. This is why you’ll commonly notice the area around the nail to be quite red and swollen after biting the nail off.

Now that we’ve discussed the clinical signs of ann activated inflammatory response, let’s address what exactly signals an inflammatory response to occur? The answer is bacterial replication and tissue damage. After getting a cut, bacteria from the surrounding environment can enter the wound, and then start replicating to grow. What’s important to understand is that when bacteria replicate, they tend to damage the surrounding tissue. Therefore, specifically bacterial replication that causes tissue destruction stimulates the immune response.

In contrast, if there are bacteria in the body that are not damaging tissue, the immune system makes a deal with those bacteria – if you don’t injure the body, then we won’t attack you. This concept is present in the gut, with the existence of the gut microbiome. The gut is filled with bacteria, but we don’t mount an immune response against this good bacteria because they do not cause tissue damage. In fact, researchers have determined that the gut microbiome is crucial to our extent of digestion as well as overall health.

This example of the gut microbiome reveals that it’s not bacterial replication but instead tissue damage that signals an inflammatory response to occur. As such, tissue damage all by itself, without associated bacteria, can stimulate an immune response because there needs to be an inflammatory response activated to repair the injured tissue. The major effector cells in this tissue repair process are macrophages. Macrophages release mediators to allow for recruitment of immune cells to the local area of the infection. Macrophages are also involved in efferocytosis, the process of consuming and removing apoptotic (dead) cells.

Having discussed the clinical manifestations and triggers of the inflammatory response, what is the basic of the inflammatory? These goals are:

1. Prevent the initial establishment of infection
2. Prevent the spread of infection from the invasion site to other non-infected body tissue
3. Recruit effector cells for assistance when the local innate cells (macrophages) are not sufficient to eliminate the infection
4. Macrophages will alert and mobilize B & T cells

In our next Immunology blog, we will dive into discussing the different phases of the immune response! Until next time!