(Selected Tables and Figures referenced, but not present in this blog
can be found in their corresponding Science Version blogs)
Back in Blog #5, we closed with a segue from innate immunity to adaptive immunity, or the more natural immunity to the acquired, more aggressive adaptive form of immunity. We talked about a “regulated” system in innate immunity and now we will “progress” (not exactly the perfect descriptor) into a “dysregulated” immune system. This adverse change in the immune systems is caused by adverse factors we mentioned towards the end of Blog #5 which you may want to review.
But first, let’s also consider 4 possible mechanisms that can reverse this negative response. First, if the removal of the bad guys, the antigen, occurs for any reason, a process called “feedback inhibition,” it reduces negative immune influences and effectively reduces and reverses dysregulation. Second, complex systems in the brain that control the immune response can regulate and reduce the problem. We’ll be talking a lot more about these neurological in Blog #17. The third mechanism is when one of the T cell types, T regulatory (Treg), reduces T helper cells which, as you may recall stimulate the B cells. So this reduction in Th cells reduces B-cell activity which could be causing the dysregulation. And finally, the fourth mechanism is a very complex genetic mechanism that we are going to postpone discussion until Blog #33 regarding cancer treatment in which complex (B cell idiotype circuit) mechanism plays a role. I think you’ll find the mechanism and its association to cancer very interesting. But let’s deal with this adaptive immunity progression here and now.
Failure to remove an offending antigen in a timely manner or a malfunction of any one of the four mechanisms described above, can lead to a negative response resulting in a clinical effect you have heard about and undoubtedly have experienced yourself somewhere along the line. It’s called “acute inflammation.” What’s developing now as adaptive immunity begins to develop is an antigen overcoming the innate system, a race to eliminate the bad guys (antigens) ensues, a race in most cases, given an otherwise healthy person, the innate immune systems will win. If, however, the underlying health of the patient is not adequate enough to sustain the aggressive activity of the adaptive immune response, things could begin to deteriorate further. All those T’s and B’s and immune chemicals now begin to initiate four types of overreactions we mentioned in the later part of the innate immune system discussion (Blog #5).
These four overreactions develop as a product of different types of antigen categories, 4 types which produce 4 specific immune cellular responses. We won’t describe each reaction yet (later in Blog #14), but simply indicate that one or more of these reactions will produce the acute inflammation I mentioned above, and something called the “inflammatory cascade” (Figure 2.1) which is a flow of chemicals, cells and proteins that will ultimately produce clinical effects we all have encountered somewhere in our lives. They include redness or vasodilation which is caused by dilated blood vessels; swelling or edema and infiltration, both caused by accumulation or diffuse discharge; and finally, ulceration or the breakdown of tissue (Figure 2.2). Interestingly, notwithstanding its negative signs and symptoms, acute inflammation can be considered a healing or protective adaptive immune process which is trying to fight off a foreign antigenic invasion. Nonetheless, because of its negative effects, the fundamental treatment for acute inflammation is the removal of the offending antigen in a timely manner and treating the clinical signs and symptoms. We use cold to reduce the redness and swelling by reducing the vasodilation and, when necessary, steroids to interrupt the chemistry of the inflammatory cascade (Figure 2.3 and 2.4). Failure to do these treatment steps can lead to the more destructive, often irreversible ulceration with associated tissue loss and even the potential for DNA disturbance. Once again, the stress creating this “dysregulated” state in tissues or organ systems from the inflammatory cascade creates the potential for a self-sustaining cycle (Figure 5.1). But the most serious consequence of acute inflammation, if not treated promptly and effectively within days or weeks, is the risk of the adaptive immune response lapsing into a chronic condition called “chronic inflammation.” While acute inflammation is only one route to chronic inflammation, there are other causes, some understood and some unknown. And as we discussed in Blog #2 (and again later in Blog #14), albeit similar in name, chronic inflammation, beyond its “chronic” duration, introduces an entirely distinct and far more dangerous path towards unremitting clinical disease.
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