Allergic individuals produce IgE because their allergen-specific helper T cells are biased toward the Th2 type, so how does this tendency develop? There is no definitive answer to this, but many immunologists believe that the Th1/Th2 bias usually develops during early childhood and, in some individuals, even before birth. The fetus derives approximately half of its genetic material from the mother and half from the father, so the fetus is effectively a “graft” – its body expresses many paternal antigens that the maternal immune system is intolerant to. Th1 helper T cells secrete TNF and IL-2, which help to activate NK cells, and IL-2 stimulates NK and CTL value-added, thus diverting maternal helper T cells away from Th1 cells. Cytokine profile differentiation is beneficial for fetal survival. And it is true that placental cells produce relatively large amounts of IL-4 and IL-10, which in turn go to the mother’s helper T cells to differentiate into Th2 cells. But these same placental cytokines can also strongly influence the fetal helper T cells, resulting in a significant tendency for the helper T cells in humans to produce Th2 cytokines at birth. Obviously, the differentiation bias of helper T cells does not persist throughout life, and eventually the Th1/Th2 cell population in most people will become balanced. Microbial infections (e.g., viral or bacterial) during early life may help to establish a balanced Th1/Th2 cell population, as these microbial infections usually trigger a Th1 response. However, there is no conclusive evidence that early microbial infections play an important role in “reordering” the immune response so that the body produces a Th1 response to allergens. Immunologists speculate that while young children are infected with microbes that strongly bias their immune response toward the Th1 class, if they are exposed to an allergen (e.g., dust mite proteins), helper T-cell guidance against that allergen will also be biased toward the Th1 class. Once the bias occurs, the feedback mechanism will tend to target the Th1 response and the resulting memory T cells will remember not only the allergen but also the Th1-type response against that class of allergen. Once a large number of biased memory cells are formed, they will be difficult to correct, and thus early exposure to infectious disease may be critical in establishing a normal immune response to environmental allergens. ”The concept of “immune bias” is consistent with an increase in allergies and a decrease in microbial infections (e.g., tuberculosis) in developed countries, and is therefore sometimes referred to as the “hygiene hypothesis. The presence of immune bias susceptibility factors in children could also explain the greater susceptibility of children born in certain months of the year to seasonal allergic reactions. In addition to environmental factors (such as early exposure to infectious diseases), genetic factors apparently also play an important role in the development of allergic susceptibility. For example, if one identical twin has allergies, the other has a 50% chance of developing allergies. Immunologists have suggested that people who are allergic to certain allergens are more likely to inherit specific MHC class II genes than those who are not, suggesting that these MHC molecules may be particularly effective in the presentation of allergens. In addition, some allergic individuals produce mutants in the IgE receptor, and it is speculated that these mutant receptors cross-link with an unusually strong signal, leading to abnormally high levels of IL-4 secretion by mast cells, which in turn stimulates IgE production. mutations in the promoter region of the IL-4 gene have been detected in some allergic individuals, and this may lead to elevated IL-4 levels. Unfortunately, allergy susceptibility genes are difficult to identify because they appear to be numerous and also vary between allergic individuals. The best current explanation for this is that the immunological basis of allergy lies in an immunomodulatory defect that strongly biases allergen-specific helper T cells toward expression of the Th2 class cytokine profile and leads to production of allergen-specific IgE. Individuals can be genetically predisposed to be more or less susceptible to allergens, and exposure to environmental factors such as microbial infections may influence whether a susceptible individual becomes atopic.