As I posted last time, receptors on the surface of cells are the antennas of the innate immune system. Embedded in membranes, they lie in wait for a substance to which they can bind. Employing complementary, they recognize their quarry by its shape and chemical nature. And when they detect a suitable prey, they stick to it and communicate their successful capture to other players so that the cell can respond appropriately.
There's an additional group of soluble receptors that hang out in the cytoplasm of cells where they can detect viral invaders that have breached the cell membrane. In all, as mentioned previously, there are upwards of 100 different receptors, each one fine tuned to bind to an appropriate target.
These receptors react to signals from two different sources. The first, as mentioned, comes from microbial invaders, like bacteria, fungi, parasites, and viruses. The second derives from the internal contents of cells that spill out when an injury occurs. In both cases the response is fine tuned such that each of the many kinds of receptors stimulates a different reaction and thus a different response.
Which cells bear these receptors? While most cells are equipped with a subset of receptors, it is the macrophage that often signals the initiation of the innate response. Macrophages, meaning "big eaters", are widely distributed in healthy tissues throughout the body. Their principal function, befitting their name, is to seek out, engulf, and digest invaders. In addition, they secrete small proteins into their surroundings whose function is to communicate information to other cells. In particular, they often announce to other cells that something is amiss. Such proteins bear the generic name "cytokines". (I promised to keep jargon down to a minimum. But "cytokine" is another term that you'll need to know).
All the general references that I've used to learn about macrophages cover them in considerable depth. However, I wanted to learn more so I tried perusing some review articles for a more definitive take on the subject.
My dip into the review article lake quickly found me lost in the weeds. As I should have expected, complications abounded. Nevertheless, I managed to capture some prize trophies as I made my way though a morass of technical details. Here they are:
First, macrophages were discovered in the nineteenth century by a Russian biologist named Metchnikoff. After piercing a transparent starfish embryo with a thorn, he found that the embryo responded by dispatching a host of large cells to the site of injury. He called these cells "macrophages" and speculated that they played a role in defense against invaders. He was awarded a Noble Prize for his discovery.
Second, it was thought for several decades that mammalian macrophages were derived from a white blood cell called a "monocyte". The theory was that all the monocytes left blood vessels and moved into tissues where they became macrophages. It turns out that this is at least partially incorrect. It appears that a considerable fraction of macrophages take up residence in tissues early in embryonic development and remain there, dividing as needed to replenish their numbers, until and through adulthood. There remains considerable controversy concerning the different roles that the resident macrophages play versus the ones that derive from monocytes.
Third, macrophages can be found in many different tissues. In each one, they play a different role and even have different names. These roles often have little to do with the defense against microbes. That makes things unnecessarily complicated for this narrative. To simplify, I'll focus almost solely on the role of the macrophage in immunity.
In brief, macrophages serve the following functions:
1. They ingest microbes by phagocytosis.
2. They ingest cells that have been killed by microbes and injury.
3. They secrete cytokines to alert other cells to come to the site of microbial entry.
4. They secrete cytokines to induce an inflammatory response.
5. They interact with the adaptive immune system.
I'll discuss these points in more detail in the next post.