Can an overactive immune system also be dangerous?

An overactive immune system is genuinely dangerous, and this is not a theoretical possibility. In several conditions, the immune response itself causes more harm than the original threat. The principle applies in infections, metabolic diseases, and even after a heart attack.

After a heart attack, a temporary inflammatory response clears away the damaged tissue. That is useful. But if that response lasts too long or becomes too strong, the heart chamber stretches and heart failure can develop. Animal studies and observations in patients show this consistently.

In a rare genetic condition called CHAPLE, a brake on the so-called complement system, a part of the immune system, is missing. Without that brake, the immune system attacks the body's own blood vessels. Children with this disease develop dangerous blood clots at an early age, lose proteins through their intestines, and fail to grow properly. This is one of the most direct pieces of evidence that an unrestrained immune response can be life-threatening.

Overactivity of so-called inflammasomes (components of the immune system that detect bacteria and damaged cells) also plays a role in common diseases. Genetic errors in these inflammasomes cause severe chronic inflammatory diseases. In addition, a link has been found in type 2 diabetes and atherosclerosis with excessive activation of this same system, presumably driven by overnutrition and metabolic problems.

In tuberculous meningitis, a study of 281 patients found that overactive neutrophils (a type of aggressive white blood cell) in the blood were associated with higher mortality. Here it is not the bacterium alone that kills, but also the body's own inflammatory response that damages the brain. This is an association, not a proven causal relationship. Finally, a zinc deficiency appears to disrupt the balance of the immune system, making the body more vulnerable to harmful overreactions. That evidence is limited and largely indirect.