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I am not a biologist, but recently while reading an article on Scholarpedia about self-organization I encountered a fascinating biological observation concerning immune response to infections. To quote the article:

Whether the resulting patterns are stable or oscillating depends on the relation of the time constants. If the antagonistic reaction has a longer time constant than the self-enhancing reaction, oscillations or burst-like activations will occur. An example is the time course of an infection: The infection with few viruses could be sufficient to trigger a sickness since the viruses replicate themselves (self-enhancement). The antagonistic reaction, mediated by the immune system, is much slower. It takes a day to become sick, but a week to become healthy again. (What appears on a first inspection as a disadvantage is in fact a good strategy. If the immune system would be much faster, an equilibrium between virus production and virus removal would be established. After a single infection we would fight for the rest of our life against the virus. However, due to the burst mode, we become sick for a short while but the virus is subsequently completely eliminated).

Since the quote may be hard to parse out of context, I'll recapitulate: The writer is asserting that the immune system's response to infections is slower than might be physically possible because such slowness actually makes the response more effective. By waiting a few days, the patient is sick for longer than they might be happy about, but when the infection goes away, it's gone for good. If the immune system responded immediately to an infection, it might result in a low-level infection that persists indefinitely.

This makes me wonder: For chronic diseases, is the reason they are chronic related to the time scale of the infection vs. that of the immune system's response? Could such diseases possibly be cured by suppressing the immune system for a time so as to get the "burst" effect alluded to in the quote above?

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    $\begingroup$ I fail to follow the logic of that quote. Furthermore, components of the immune system are active as soon as an infection is recognized. $\endgroup$ – canadianer Jun 1 '15 at 3:13
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    $\begingroup$ What should be the benefit of this delay? It raises the chances that our body is overwhelmed by the virus and dies. The delay of the adaptive immune system is simply caused by the fact that it needs some time to launch a highly specific immune response. The innate immune system (you could call this our first line of defense if you like) acts very fast and almost immediately. Additionally viruses get used to our immune system and adapt, see HIV for example. I can make this into a full answer later today. $\endgroup$ – Chris Jun 1 '15 at 6:57
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    $\begingroup$ @canadianer and everybody wondering about the logic behind the q: this type of equilibrium is best known to biologists from the Lotka Volterra rule. Start out with a balanced ecosystem, say 100 rabbits and 10 wolves, and you'll have rabbits and wolves forever, in changing ratios. But if you start with 100 rabbits and 50 wolves, you'll run out of rabbits before the wolf number goes down. The assumption behind the q is that waiting for a large virus population elicits an overproportionally "large" immune response which kills all viruses instead of the supposedly "small" response to few viruses. $\endgroup$ – rumtscho Jun 2 '15 at 19:25
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    $\begingroup$ @rumtscho I understand what the quote is saying, but the immune system does not follow a predator-prey relationship. The quote suggests that a delayed immune response is an adaptive advantage rather than a mechanistic requirement. That is the logic I did not follow, with the implication that it is incorrect. $\endgroup$ – canadianer Jun 2 '15 at 19:30
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    $\begingroup$ @canadianer I see. Then I had misunderstood your first comment - it now seems we agree on what the exact problem is with the quote. I thought it important to write it out explicitly, because when somebody presents with a wrong idea, it is frequently best to hunt down the exact place where a wrong assumption is used, else he is unlikely to understand the correct explanation. And sometimes the experts have the hardest time to spot the problem in understanding, because they know the subject so well, they can't imagine that somebody will make an "obviously" wrong assumption. $\endgroup$ – rumtscho Jun 2 '15 at 19:38
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I think the person who wrote the quote does not really understand how an immune response is happening. There is no real "waiting period" until the immune system starts attacking the virus (or bacteria or whatever), this happens instantaneously when the virus is recognized.

To do so, we have two, independent systems, the innate immune system and the adaptive immune system. The innate imune system reacts immediately and launches a unspecific, but still very effective answer to a virus. The adaptive immune system delivers a highly specific (via antibodies) immune response, which takes a while since the generation of specific antibodies takes some time (the body produces antibodies which are then matched against the virus). It works like shown in the figure (from here):

enter image description here

It is also the adaptive immune system which mediates the long-lived immunity against pathogens which have triggered a immune response. Once you get in contact with such a pathogen again, the adaptive immune system can react immediately and protect you. This is also how vaccinations work.

Both immune answers start immediately upon pathogen recognition, there is not benefit in delaying (or suppressing) this immune response. In contrary, this is highly dangerous for the individual, as you can see in persons, which have received a transplant. These need to suppress their immune system in order to prevent a transplant rejection, but at the price that they get sick a lot easier.

However, there are some diseases, where a partly modulation of the immune system is beneficial. These are autoimmune diseases where the immune system is directed against the own body. Examples would be rheumatoid and reactive athritis.

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No, this wouldn't happen. The logic of your proposition assumes that chronic diseases are caused by the strength of the immune response being insufficient to kill off the virus, resulting in a long-term equilibrium between the amount of virus particles produced and the amount of virus particles killed.

In reality, this is not how chronic diseases work. Only a small amount of chronic diseases are caused by viruses. There are many which have other causes, not all of which can be defended against by the immune system - e.g. chronic depression is not curable by immune response.

But even if we focus on chronic virus infections such as herpes simplex, they are not sustained by the mechanism you describe. They happen due to the fact that our immune system simply does not know how to get them out of their new home within our body, they are just that good at hiding during latency. So even if you could cause a strong immune response all at once, it wouldn't kill all viruses at once.

Even if we have viruses whose serum presence depends on a constant growth vs. destruction dynamic (I don't know if these exist at all), an overly strong immune response won't be that good for the human host. Inflammation is a dangerous state, most of the unpleasant feeling you get when you are sick is not due to the virus itself but due to your own immune response, which causes the fever, muscle pains etc. associated with many acute infectious diseases. If we were to ramp this up, you'd probably get a fever high enough to cook you alive, or some other undesirable effects.


On a side note, I also doubt the author's argument which suggests that long-ish convalescence times evolved because shorter ones would leave the system in an undesirable equilibrium. Sure, an alternative reality is thinkable where the innate and adaptive responses described by Chris occur much stronger at the beginning, leading to steeper curves and shorter healing times. But the simpler explanation for that is that 1) our immune system is not perfect, and it evolved to the highest healing speed it could achieve, and 2) an immune system with higher acceleration would have been way too costly in terms of resources available to the body. An evolutionary advantage in having a low-acceleration immune system is a strong assumption for which I see no support, especially considering that the residual immunity provided by the adaptive immune system would prevent the dynamic equilibrium suggested in your quote.

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