Inflammation

So, we turn, now, to our first actual process. Being part of the innate immune response, inflammation is not a response to a specific pathogen, but to pathogens in general. It may also result as a response to tissue damage (e.g. as caused by a cut, or a burn) and tissue death; a chemical agent; or, in some cases, one's own cells which are wrongly identified as a threat. Inflammation is characterised by the presence of pain, heat, redness, swelling and, ultimately, dysfunction of the affected area. It has important purposes - even if it can be quite uncomfortable for an individual. The role of inflammation is, ultimately, to destroy any pathogens or other potentially harmful foreign bodies. It does this by containing whatever initiated the response and "recruiting" resources and immunocompetent cells to destroy it. It also serves to remove any tissue which may have been damaged - this allows the affected area to heal effectively.

We will see how this is achieved presently; but it is important to point out that chronic or excessive inflammation can result in very serious problems; this is because the inflammatory response - while helpful - initiates events which can be harmful to health if they are prolonged, or excessive. This can result in, for example, tissue damage and can result from a failure of the regulatory mechanisms of the inflammatory response, or an inability to remove the initiator of the response. Other problems which can result from inflammation include allergic reactions and anaphylaxis. Allergic reactions occur when a harmless agent, such as dust, pollen, or rubber, is misidentified as a threat. An excessive response can result which, if uncontained and systemic - anaphylaxis - can cause serious harm. Even without anaphylaxis, allergies can still be disruptive, for obvious reasons. An individual may need to avoid certain foods, or materials, which can be difficult and affect everyday life. The inflammatory response is also involved in autoimmune disorders - where normal cells of the body are perceived as pathogens and are attacked. Apart from the damage to the cells themselves, this can result in chronic inflammation (for the inflammatory response cannot effectively destroy all of these cells - a good thing) and this is the case with a number of debilitating diseases, such as rheumatoid arthritis. Inflammation caused by substances which can't be removed, such as wood, metal and asbestos fibres, can also progress to chronic inflammation, as we've already seen. Since the foreign body cannot be removed, the inflammatory response is not halted.

How, then, does the inflammatory response work and what, in fact, does it do? Vasodilation (enlarging of the blood vessels) in the local area is one of the first responses. This increases blood flow through the region and is the cause of the redness and the heat. The blood flow increases because the same amount of blood is being pushed (by the heart) through a wider blood vessel, so there is less resistance to the flow of blood. If you pour water out of a bottle and into a cup, you will notice that if you then pour that water out of the cup, the cup will empty much faster. This is because the opening at the top of the cup is much wider than the opening at the top of the bottle. It's the same principle. The increased blood flow increases the presence of cells involved in the immune response, for these are carried in the blood. The walls of the blood vessels (the endothelium) in the affected area also increase in permeability. The cells reorientate to allow important substances such as clotting factors (which impede the spread of the infection) and proteins which can destroy the pathogens (antibodies) to move from the blood vessels into the interstitial fluid - a fluid which surrounds all cells. These substances are transferred through a fluid called exudate and its loss from the blood flow results in a decreased level of blood plasma. As a result, the cells in the blood become more concentrated and the blood more viscous. This then causes a drop in the speed of the blood flow, which causes leukocytes (or white blood cells, which are involved in destroying the pathogen) to drop out of the axial flow. These cells adhere to the endothelium and can pass through it to the site of the infection. This is how the inflammatory response "recruits" the leukocytes. Ordinarily, leukocytes would be retained in the blood flow as shear prevents them from marginating (the name given to this process) along the endothelium. Thus, important proteins are now present in the liquid around damaged cells, wherein also are the pathogens. This allows the process of clearing the infection to begin.

This accumulation of fluid, referred to as oedema, is the cause of swelling often associated with inflammation, and the distortion of tissue caused by the swelling is one of the principle causes of pain. Certain chemicals involved in mediating inflammation - such as bradykinin, which causes vasodilation - also cause the body to experience pain. Serotonin and prostaglandins are other examples. The swellings are also involved in the loss of function which can, in extreme cases, result from the inflammatory response. Function may be lost either due to the pain caused by these swellings, or - simply - due to the swelling inhibiting movement.

Another common aspect of the inflammatory response is fever, which it has been argued may help the activity of the immune system and hinder some pathogens, by increasing body temperature. Fever is brought about by cytokines, which we will look at in more detail shortly, and is another cause of the experience of heat.

Alongside vasodilation and other vascular changes brought about by the inflammatory response, cellular changes are the other key component of the inflammatory response. The response results in the release of chemical signals (chemotactic factors) which can draw cells that attack pathogens to the site of the infection. These chemotactic factors are cytokines - proteins (or peptides, or glycoproteins) which are involved in the regulation of the immune response. Where there is significant tissue damage, vast stores of neutrophils, which are involved in the destruction of cells, are released from bone marrow and drawn to the site of the infection by chemotactic factors. This process is known as chemotaxis and it is not at all simple to understand. Should inflammation persist (usually after 24-28 hours), monocytes will also be drawn to the area of infection. These are cells which develop into macrophages, which destroy pathogens (and, also, dead cells) by digesting them (see Innate immunity). And so it is (partly) that the required cells come to be in the required place and they can then set about dealing with the cause of the inflammation and, ideally, removing it.

Here is where I stop briefly. I will pick up the discussion of inflammation in the post after next (feel free to skip the next post and move straight on to that one). The next post, meanwhile, will be a discussion of chemotaxis. Chemotaxis is very important and it makes sense to talk about it now. It is, though, a separate issue - hence the separate post - and can be read about later.