I was reading an article recently debunking the idea of 'boosting' your immune system. It occurred to me that - presuming it's right - our immune systems are all pretty much the same (with the exception of the immunocompromised). Given this, I wondered why there is such a disparity in how people respond to pathogens or carcinogens.

Most people would be quite happy, for example, to say that poor food hygiene causes food poisoning or that smoking causes cancer, but in actual fact, most of the time they don't. People who have poor food hygiene standards have them every day, but they're not sick every day, they're sick once in a while. Only 25% of heavy smokers actually get lung cancer, even with something like Asbestos, only 1 in 10 former Asbestos workers actually get Mesothelioma.

What is it that protects most people from these diseases despite definitely encountering the pathogen/carcinogen concerned?

I realise the most obvious answer is the immune system, but that just shifts the question to why this doesn't protect everyone all the time. Presumably the immune system doesn't just have a day off every now and again

  • $\begingroup$ It is indeed our immune system. And for cancer it catches most (probably more than 99.9%) of the cells going wild. But still, once in every while one of these cells escapes and causes problems. The same with the stuff in the environment you live in. You are used to it, your immune system is trained on it. Only new pathogens will cause problems. Or you, getting into a new environment. $\endgroup$
    – Chris
    Commented Sep 15, 2016 at 13:12
  • $\begingroup$ @Chris. As I said in the question, I'm aware of the role of the immune system. What I'm asking is by what mechanism exactly does it fail from time to time? $\endgroup$
    – Isaacson
    Commented Sep 15, 2016 at 15:45

2 Answers 2


This answer will address only cancer.

There is no such thing as standardized exposure to carcinogens in humans; while it would go a long way to answering your question, it would be unethical.

Also, it is unlikely that two people who do consume identical amounts of a carcinogen have identical environments or identical genetics.

Cancer used to be thought of as a carcinogen-host interaction; expose a (rodent, in my studies) to adequate levels of a carcinogen and cancer will occur. We tried to figure out exactly why. Then it was thought of as a host + environment (This was decades ago.) The immune system was found to play a role; another level of complexity was added.

Mapping the entire human genome has made us aware of how simplistic these (and most) models were. There are tumor-suppressor genes. There are genes that matabolize carcinogens differently from other genes. There are genes that direct repair of DNA better than other genes. The possibilities are just beginning to surface.

To answer your question more directly,

Although many studies have focused on carcinogen metabolism and cancer risk, more recent studies are considering DNA repair.

I would not go so far as to label DNA repair as Immunology.

I don't know why my father, who had a 120 pack year history of smoking, had absolutely no ill effects (not a trace of COPD, and certainly not cancer, no heart disease, CVD or other) and why my mother had COPD at a 40 pack-year history, but I'm sure it was genetic.

Sporadic cancers are caused by genen-environmentn interactions rather than a dominant effect by a specific gene, environmental exposure, or gene-environment interaction. New paradigms, where we categorize genes as caretaker or gatekeeper genes, will allow for new hypotheses to be tested and will require advanced methods of analysis.

And, in another study,

Three meta-analyses report 35% to 50% increases in breast cancer risk for long-term smokers with N-acetyltransferase 2 gene (NAT2) slow acetylation genotypes.

Cancer Risk and Low-Penetrance Susceptibility Genes in Gene-Environment Interactions
Integrative Epidemiology: From Risk Assessment to Outcome Prediction
Active smoking and secondhand smoke increase breast cancer risk: the report of the Canadian Expert Panel on Tobacco Smoke and Breast Cancer Risk (2009)

  • $\begingroup$ Thanks for the thorough answer, if I could just ask for clarification on one point. If I understand correctly, you're saying that response to a given dose of carcinogen is a result of - host environment, host immune response and host genetics (discovered in that order). If that's the case, to take lung cancer and smoking for example. Heavy smoking only produces cancer in about 25% of smokers. The genes you've pointed to in your last study give a 35-50% increased risk, that still leaves a huge amount of resistance to cancer unaccounted for, is that correct? $\endgroup$
    – Isaacson
    Commented Nov 15, 2016 at 8:19
  • $\begingroup$ Also, as may be clear from my comments to the last answer, I'm interested in the research into the host response in terms of factors that a host could control. Is the move to genetic studies a result of the general trend in research since the human genome project, or have there been studies actually eliminating other non-genetic host factors? $\endgroup$
    – Isaacson
    Commented Nov 15, 2016 at 8:26
  • $\begingroup$ @Isaacson - Yes, you're correct. There is also the possibility, though, that a cancer-causing mutation will not occur in 100% of the population exposed to a carcinogen. No, none of the other factors have been eliminated, but they have been, say, relatively dwarfed by genetic factors, for example, in breast cancer, the presence of estrogen and progesterone receptors, multiple copies of the HER2 gene, microRNA, DNA methylation, presence of the BRCA1 gene, and mutations in several other important genes. See, e.g. nature.com/nature/journal/v490/n7418/full/nature11412.html $\endgroup$ Commented Nov 15, 2016 at 13:13

Intro courses on pathogens often show a triangle representing interactions between host, environment, and pathogen to help explain why outcomes are so diverse. Each of those parameters is very diverse, so the combination of the three is even more diverse. At a simple level, you could think about one fit, well-rested person exposed to a low concentration of pathogen, in a warm, comfortable environment, and compare to a stressed, malnourished person in a hot, humid environment, exposed to a large bolus of pathogen.

As well as concentration, pathogens individually vary in their virulence. Individuals all have unique immune systems, with tremendous diversity (the immune system contains genes that are by far the most variable in human -- or virtually any vertebrate -- populations). And environmental effects interact with both sides to enhance or reduce susceptibility in many ways.

It's a set of many overlapping complex systems, basically. Sometimes it's possible to point to a specific combination of causes, but more often we just see a few people getting sick while most remain healthy, and never clearly understand why.

  • $\begingroup$ I get most of what you're saying, but your mention of the fit well-rested person seems to suggest that one can, in fact boost your immune system by being fitter, getting rest etc. If that's the case and the figures I mention in the question are accurate, then when people talk about the 'cause' of a disease it would be more correct to say that lack of fitness and stress was the main cause with everything else only secondary. $\endgroup$
    – Isaacson
    Commented Sep 15, 2016 at 16:06
  • $\begingroup$ First, the notion that "lack of fitness and stress was the main cause" is not in my answer; I listed them as among many potential influences, not by any means a main cause; it's telling that you assumed in spite of the phrasing that this is a "main cause", because it ties into a common (misguided) notion that disease has a moral aspect, people get sick because it's their fault, it's a punishment, and recovery is a sign of virtue. $\endgroup$
    – iayork
    Commented Sep 15, 2016 at 17:56
  • $\begingroup$ More importantly, it's not a question of "boosting" immunity. People have a normal default level that can be damaged, not a normal level that can be boosted. You can, to take an obvious example, take immunosuppressive drugs, like catabolic steroids. Among that common causes of mild to moderate immune suppression, lack of sleep is one well-supported cause; morbid obesity another. $\endgroup$
    – iayork
    Commented Sep 15, 2016 at 17:56
  • $\begingroup$ My intention was not to make a moral point, but a statistical one. It's like saying a runner won the race because he turned up. Turning up was certainly a requirement, but it's not why he won because other runners also turned up and they did not win. The thing we ascribe as the cause is what sets that runner apart from the others. I don't see why the same is not true when we ascribe a cause to disease. $\endgroup$
    – Isaacson
    Commented Sep 15, 2016 at 21:44
  • 1
    $\begingroup$ I'm not sure what your issue is. I tried to indicate that the interactions between host, pathogen, and environment are extremely complicated. You promptly claimed that "lack of fitness and stress was the main cause", which is exactly the opposite of what I said, and then you're accusing me of oversimplifying and focusing on a generic cause. As far as looking for why most survive, that is an intense field of research, but I'm not particularly interested in trying to explain it to someone who is trying to hard to force my answers into their own personal agenda. $\endgroup$
    – iayork
    Commented Sep 16, 2016 at 12:28

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