Autoimmune condition as collective punishment? - (Aug/14/2018 )
Hello, my question is rather unusual, even queer:
The immune system is so sophisticated, “byzantine”, and there seem to be no generalizing theory to structure our knowledge about it. However, in most contemporary textbooks and papers, we see one informal and implicit generalization – which is the “personification” of cells, and visualization of complex systems as an organized and motivated “societies” of cells, (not unlike human societies or agencies.)
E.g., tumor cells are imagined as motivated beings, with their purpose to take advantage of other cells and resources of the body, in order to grow and proliferate. They even reveal a sort of “intelligence” – as they seem to invent new strategies to bypass immune responses and even recruit immune cells for their own ends, by certain cytokine signals, etc. (one can hardly believe that this can be explained by random mutations only). On the other hand, the immune system is also imagined as an organized polity, (not unlike police of a state) also inventing strategies, motivated to block those illicit activities .
Can we take all this ‘personified cells’ seriously? Can we formalize this informal analogy and make it rigorous? Can we isolate the working part of it, by some abstraction? (Similar informal approach, involving personification, is quite common in brain science as well as many other fields, in fact psychoanalysis, etc.)
Can this ‘personification theory’ have any predictive power? For instance, in human society we sometimes see the cases of “collective punishment”, or “collective suppression” – when a harmful activity is conducted by unknown persons, hidden among a certain social group, (while the rest of the group is harmless and useful for society) then the state police (or similar agency) may suppress and punish the group as a whole. And under some conditions this is a justifiable strategy, until the guilty individuals were detected. So, we predict a similar phenomenon within human body: if harmful activity cannot be pinned down to individual cells with absolute certainty, then immune system must suppress the whole surrounding area or the whole tissue.
And my question is – could some autoimmune conditions be explained by this scenario? I.e., are there any indications towards immune system attacking a normal tissue because in fact not all of the tissue is normal, but some of the cells hidden among it are doing something illicit, not yet detectable by medical tests? Please refer me to any papers that may deal with this question!
Some simple cases of such “collective suppression” are clearly visible – e.g. basophiles and eosinophiles killing healthy cells around a large parasite or a splinter of wood under the skin, reducing both friend and foe to pus; or gamma interferon suppressing protein synthesis and division in healthy uninfected cells, just on the reason that virus infected cells were detected somewhere in vicinity, in order to reduce the probability of virus proliferation.
Sometimes, indeed, a correlation between autoimmune disorder and malignant transformations of the target tissue is observed. E.g. between SAA and bone marrow cancers, leucosis. In other cases, the causes behind autoimmune condition look too mechanical and simple for any social analogy.
Please advice and refer me to any relevant papers and books!
I would'n go for this in cells.
AFAIk it would be more misleading to attribue to cells human-like motivations or such, immune system may be very complex, but considering known cellular events that are already known would give better prediction value.
As for cancer cells, cancer is just evolution gone wild and without previous binds to a tissue or orgnism itself. Multicellular organisms neede to have a very strict policing, to keep tissues cooperating rather than each of them trying to get the most. The cancer tissue is rather sucessfull in a very short timespan, but as a result the whole organism dies. And possibly can't reproduce. Cells can't reproduce on their own. This shows how not "inteligent" the cancer tissues is, it can't forsee it's own end by growing "selfishly".
And as for autoimmune, immune system is very variable across the population and I thing that is actually desired. Different HLAs, different affinities to pathogens or agressivness of immune system. Each of that combinations may or may not be beneficial in certain situations, but the population itself, if wide enough, will always survive. Some variants protective against HIV or those who didn't die of plague epidemics in the past, those exist, but may pose disadvantages in some other settings. The very same is for bacteria, some of them do carry an antibiotic resistance for example, but those are usually disadvataged when no atb is present, so they thrive worse.
Hypothesis goes, that variants with higer autoimmune risk are actually beneficial against pathogens that were present in the past, or are just beter UNTIL they screw up. HLA-DQ2 is the risk factor for coeliac disease, but 1/3 of European population has it (and only a little fraction of these actually do get coeliac disease). More agressive immune system is better when you have to fight more pathogens, theory goes that when pathogens are not present, they pose higher threat to its own tissues, since they are not occupied otherwise. Also some events do happen by chance all the time, being it a mistaken cross-reactivity that can trigger an autoimmune response, or a DNA lession that may be on the begginng of a cancer growth, cumulatively the older person is, the more of these he gets, and tissues grow older and errors happen... no wonder cancer is like a major reason of death. In my oppinion, if all other diseases were prevented, everyone would just sooner or later died on some form of cancer (or neurodegenerative disiease, which is also a part of aging, "uncleaned garbage" damage the most sensitive neuronal tissue and organism start to fall apart), because the pressure for survival is just the only constant, and have to be policed or someone would escape and overgrow. But cancer is also balanced with increased aging, and if the balance is shifted in any of those directions, organism dies earlier that it could.
Yes , I think I know what you mean – to attach human features is the way to get paranoid, not scientific. One must be careful when imagining cells with tiny pairs of human arms and legs!
But anyhow, serious modern books are literary full of this cell-to-person analogy, (usually implicit), so we must face it and consider it consciously. It is often even hard to express a scientific thought without using such ‘sociological’ words. How would you do without the word ‘policing’ (‘Multicellular organisms need to have a very strict policing’), with what word could you substitute it? And cells are, without any stretching, full-fledged living beings, (human cells no less than any amoeba), supposedly with their strategies and motivations. May be ‘animism’ here would be a more apt term, than ‘personification’. This can be just our restricted way of understanding – to personify every complex object; but then, anyhow, we have to analyze our thinking, to overcome the restriction. Or this can be a consistent analogy, and then we also have to study it to make use of it.
Cellular events that are already known, -- they are amazingly many and they are studied down to molecules! But one have to remember, that this will never allow us to model and simulate these events on a classical computer, no matter how powerful. Modeling of a quantum system of many particles is a hard-computable task, in principle. So we have no hope for computable, ‘mechanical’ models in the future, -- and thus we need some other approaches.
One way is to speculate very accurately, and rigorously define all concepts, like abstract ‘person’ that would suit both a human person and a cell.
But the other way to avoid paranoia is to take all this discussion as a game to play, and do it with some humor ;-) What if I say that societies, like nations and states, are also subject to ‘aging’, similar to that of multicellular bodies? (Some historians even determine their characteristic lifespan). And aging nation/state, analogously, develops ‘immune’ problems – low resistance to intruders, who sometimes form rapidly proliferating, but economically useless and ‘selfish’ (semi-criminal) communities, that draw and drain common resources? And such ‘aged’ states often protect these communities legally, by police, against other, their own citizens, who are discontent with the situation (sometimes looks masochistic). Does this not remind tumor growth, that recruits healthy immune cells?
Yes, I of course agree that some gene alleles may give various advantages, at the cost of increased risk of autoimmune disorders or cancers. But then, nations also have different ‘characters’, e.g. some are more solid in harsh conditions, at the cost of being prone for suppression of their own loyal citizens, etc.
Thank you, please take this with humor, and maybe there is a something under it!
(It is even more exciting to play these analogies in brain science, psychoanalysis, and the like, I will try it some time.)