【正文】 he importance of immunological sensitization and tolerance ? Recognition that tolerance not sensitization is the critical step in allergy prevention ? Finding that exposure to the allergenic food at an optimum stage is probably a critical step in allergy prevention ? Recognition that tolerance can be induced after allergy has been established – leading to important measures for allergy management 8 Allergy is a Response of the Immune System ? Our immune systems are designed to protect the body from invasion by foreign materials ? All foods contain proteins – derived from plants and animals – all of which are foreign to the human body ? In order for food to be absorbed, metabolized, and utilized by the body, the immune system needs to be “educated” that the foreign material is safe ________ Herz 2022 9 Education of the Immune System ? Involves a plex series of immunological reactions controlled by T cell lymphocytes (T cells) ? T helper (Th) cells detect foreign proteins (antigens) in any form ? T cells then trigger a series of immunological reactions, mediated by cytokines (the “control chemicals” of the immune system) _________ Joneja 2022 10 Thelper Cell Subclasses ? There are two subclasses of Thelper cells ? Th1 ? Th2 ? Each Th cell type produces its own specific set of cytokines ? The types of cytokines generated determine the resulting immune response ? Th1 principally INF? ? Th2 principally IL4 11 Role of Thelper Cell Subtypes ? Th1 triggers the protective response to a pathogen such as a virus or bacterium ? IgM, IgG, IgA antibodies are produced ? Th2 is responsible for the allergic (hypersensitivity) reaction ? IgE antibodies are produced 12 T cells involved in Oral Tolerance ? T cell response depends on the type of T helper cell that is activated ? Latest research indicates that T cells that produce a cytokine called TGF? are important in inducing oral tolerance ? Sometimes called Th3 cells ? T cells that produce IL10 and IL13 may also be involved in tolerance ? These also regulate immune response to resident microflora, preventing the usual immune inflammatory response to microanisms ___________________ Strobel and Mowat 2022 13 Oral Tolerance ? “Education” of the T cells to not respond to that food protein when it enters via the oral route – called oral tolerance ? Contrasts with the active immune responses needed to protect the gut against continual bombardment by invading pathogens and their products (toxins, etc) ? Also contrasts with the reduced responsiveness to the millions of microanisms that are permanent residents of the large bowel ? T cells involved in these processes are called regulator T cells (Treg) 14 Prevention of Food Allergy in Clinical Practice Significant change in directives within the past 5 years: ? Previously: Avoidance of allergen to prevent sensitization (allergenspecific IgE) ? Current: Active stimulation of the immature immune system to induce tolerance of the antigens in food ________________ Rautava et al 2022 15 Factors Predictive of Allergy: High and Low risk Groups ? Many factors investigated as possible predictive markers for allergy ? Only significant variable in studies: Family history of allergy (all types) ? High risk for allergy: ? One first degree relative with diagnosed allergy (IgEmediated) of any type ? Firstdegree relative: parent or sibling 16 Does Atopic Disease Start in Fetal Life? ? Fetal cytokines are skewed to the Th2 type of response ? Suggested that this may guard against rejection of the “foreign” fetus by the mother’s immune system ? IgE occurs from as early as 11 weeks gestation and can be detected in cord blood _____________ Jones et al 2022 17 Does Atopic Disease Start in Fetal Life? (continued) ? At birth neonates have low INF? and tend to produce the cytokines associated with Th2 response, especially IL4 ? So why do all neonates not have allergy? 18 Does Atopic Disease Start in Fetal Life? (continued) ? New research indicates that the immune system of the mother may play a very important role in expression of allergy in the neonate and infant ? IgG crosses the placenta。 IgG3) can inhibit IgE response 19 Significance in Practice