Defining Danger

For many years immunologists generally accepted the model in which the immune system is able to distinguish "self" from "non-self," tolerating the former and attacking the latter. In many ways, this model makes a great deal of sense. For example, simple observation shows that a strong response is mounted against invading microorganisms, but the

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immune system generally does not attack a person's own healthy cells. There are, however, significant flaws in this model, such as the fact that the body does not mount a response against a developing fetus, which is obviously "non-self."

A new hypothesis, proposed in the last decade and the cause of much excitement, suggests that the immune system does not mount a response against "non-self" per se, but instead attacks foreign antigens only if they are associated with tissue damage or other signs of "danger." Foreign materials not linked with such signals are tolerated. This danger model opens the door to exciting new ideas regarding mechanisms regulating— and methods for treatment of—cancers, allergies, and autoimmune diseases. It is also impacting vaccine development and tissue transplantation strategies.

According to the danger model, a cancerous cell will not be recognized by the immune system as a threat, even if it produces abnormal proteins, unless some sort of "danger" signal is also present. This raises the possibility that scientists may be able to introduce such a danger signal. Coupled with a vaccine against an abnormal protein that characterizes the cancerous cell, this may provide an effective treatment for cancer. An opposite strategy might help in allergy treatment. Allergens are relatively innocuous substances such as mites, fungi, and plant pollens that often have some proteolytic activity. This activity can cause some local damage, triggering an unwarranted immune response. Hiding or minimizing the "danger" signals might help promote tolerance to these compounds. Tolerance is an important aspect in the prevention of transplant rejection as well. The surgical procedures themselves cause tissue damage, eliciting an immune response against the MHC molecules of the donor tissues. Perhaps employing drugs that dampen damaging immune responses while also stimulating tolerance could minimize rejection of transplants. Similar strategies might be useful for treating autoimmune diseases.

51 Ways to Reduce Allergies

51 Ways to Reduce Allergies

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