The next component of the innate immune system that I learned about was the complement system. To get a good grasp of how it works, you'll need to study the picture on the right. What you're looking at is a cartoon of a self-operating napkin, a "Rube Goldberg Machine". Goldberg was a prominent cartoonist in the early to middle part of the twentieth century. He "invented" and displayed the schematics for a series of complicated and impractical machines that worked by one component triggering the next, one after another, in a long series of reactions. It turns out that the immune system (and many other biochemical and physiological processes) work in a similar manner, but are even more complicated. That's because most of Goldberg's machines utilize a linear sequence (A -> B -> C -> D and so on), while biological processes may require multiple inputs at B, C, or D in order to proceed to the next step. The complement system in particular not only utilizes multiple inputs, but it also includes steps that feedback upon itself. It also makes use of amplification, where a small input results in a larger result. I expand upon these concepts below.
While trying to master the intricacies of the complement system, I began to think more upon an issue that I'd faced in the past and will undoubtedly have to address in the future. It is: How much detail should I dive into in discussing this subject, or for that matter, any subject? It seems like a teacher has to answer a host of questions in coming to a decision about this problem. How much time (or space) should be devoted to this matter? What's the attention span of the students? How much material can a student retain? Isn't it more important to leave students with an understanding of the major principles, rather than muddy the waters with details? But aren't the details interesting in themselves? For what purpose are the students learning this material?
I'm not sure that I have any good answers to any of these questions. In what follows, I'll first try to elucidate the major take home lessons. For some this may be sufficient. Then I'll discuss the subject in more detail. It may be that you might want to just skim this material.
In contrast to the cell-based innate reactions that I've covered previously, the complement system consists of 30 or so proteins that are manufactured largely in the liver and that circulate in the blood. Credit for discovering complement is widely attributed to the Belgian-born microbiologist, Jules Jean Baptiste Vincent Bordet, who spent most of his research career working at the Pasteur Institute. In the very last part of the nineteenth century he found that he could separate the immune response into two parts, one of which was due to the action of antibodies. The other, easily destroyed by heat, "complemented" the first, aiding in its ability to attack invading microbes. This work, the beginning of a distinguished career, resulting in his being awarded the Nobel Prize in 1919.
The complement system is complex, but here are the major principles. In the next post, I'll delve into the details.
Living things of all sorts commonly make use of proteolytic cascades to perform many functions. For example, blood clotting and programmed cell death (also called apotposis) are two other processes that utilize this mechanism to accomplish their tasks.
What is it? Some enzymes are synthesized in a form in which they are inactive. In particular, proteolytic enzymes (enzymes that cleave proteins) are often synthesized in this way because otherwise they may cause injury to innocent cell bystanders. In a proteolytic cascade, a signal to inactive enzymes may cause them to become activated, often by another proteolytic enzyme, thereby acquiring enzyme activity themselves, and thus starting a chain reaction. In turn, these newly activated enzymes may cleave another set of inactive proteolytic enzymes thus continuing the chain reaction, and amplifying the original signal. I'll describe the actual players in the proteolytic cascade that characterizes the complement system in the next post.
I've discussed the inflammatory response previously without specifically defining it. It occurs when macrophages detect a foreign attack an injury occurs. They and surrounding cells respond by secreting cytokines. In turn, these recruit neutrophils to the site of infection, cause an increase in blood flow, and increase the permeability of small blood vessels. Inflammation is marked by redness, swelling, an increase in temperature at the site, and pain.
In the next post, I'll expand upon these fundamental principles.