Another important aspect of the effectiveness of both reactions is that all elements of the immune system react in a coordinated manner and at the correct intensity. A weak reaction will lead to rapid spread of the pathogen. And at the opposite extreme, excessive intensity also causes serious problems by creating a hyperinflammatory environment, as occurs in the response to Covid-19.
Genetic or environmental factors?
We know that not all of us react the same way to infection. But why? What factors determine the reaction? Are they genetic or environmental?
In an attempt to answer these questions, French researchers many years ago launched the Milieu Intérieur project, for which they recruited a group of 1,000 people who were deliberately genetically homogeneous. They analyzed whether variable immune responses were due to genetic or environmental factors such as age, gender, body mass index, previous infections, etc.
The answer is that innate immunity is largely determined by genetic factors, while they and other researchers have found that environmental factors, especially age and gender, alter specific immunity.
Confirmed: Tobacco alters immune response
Tobacco is an environmental factor that contributes to the development of many lung pathologies, including aggravating pneumonia and complicating the response to bacteria. But in addition, tobacco is also associated with many other diseases, such as vascular pathologies or the appearance of certain tumors.
For all these reasons, researchers from the Milieu Intérieur consortium included this parameter in their search for new environmental factors that could explain variability in the immune response. After obtaining immune cells from 1,000 people belonging to this cohort, they exposed them to various agents that stimulate a nonspecific response (microbes, fungi or viruses), as well as other agents that cause a specific response. The response caused by stimulation with each agent was measured by the release of soluble substances that immune cells produce when activated (cytokines), which play an important role from a clinical point of view.
The researchers grouped responses based on 136 environmental factors and found that previous cytomegalovirus infections (a very common infection), body mass index, and smoking were the factors most associated with altered responses. But among them, tobacco was the most powerful environmental factor and the only one that equaled the influence of those others that we can do nothing about, such as age and genetics. Thus, tobacco significantly modified both specific and nonspecific immune responses.
Big surprise
But the big surprise was that former smokers and other people who remained active were studied separately. Thus, they saw that changes associated with the nonspecific response normalized soon after quitting smoking, while changes caused by the specific response persisted for many years after quitting tobacco.
That is, being a former smoker will compromise the effectiveness of the immune response for a long time. Bad memory, no doubt.
How does damage to the immune response occur?
But how does tobacco cause such a profound change in the immune response? In search of answers, researchers analyzed the mechanisms of gene regulation, that is, those processes that determine whether a gene will be expressed more or less. Among these mechanisms is one known as DNA methylation.
Typically, although not always, excessive addition of methyl groups to DNA (hypermethylation) results in suppression of that gene, while the opposite process (hypomethylation) is usually associated with vigorous expression of that gene.
Well, French researchers found that some genes important for the specific response of active smokers were hypomethylated compared to non-smokers. Former smokers, in turn, showed an intermediate state of methylation that depended on the amount and length of time they smoked.
The conclusion is that smokers create a generalized inflammatory environment that makes the immune response ineffective when we experience an infection. Moreover, it may contribute to the development of autoimmunity, similar to what we are beginning to see in chronic obstructive pulmonary disease, a very common disease clearly associated with tobacco smoking.
And in tumors?
But that’s not all: this mechanism may explain, at least in part, why tobacco is a very potent risk factor for many tumors other than lung cancer. An ineffective antitumor immune response may allow tumor cells to multiply uncontrollably.
It may also be that hypomethylation affects genes that control the cell cycle and ultimately leads to cell transformation and cancer.
Without a doubt, these are good reasons to quit smoking as soon as possible.