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Jorge is allergic to peanuts. Explain how the immune system will react when Jorge eats a peanut.

Question

Jorge is allergic to peanuts. Explain how the immune system will react when Jorge eats a peanut.

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Solution

  1. Ingestion: When Jorge eats a peanut, the proteins in the peanut are broken down during digestion into smaller components, including allergens.

  2. Recognition: Jorge's immune system recognizes these allergens as harmful substances, even though they are not. This is due to a mistake in the immune system's recognition process.

  3. Activation: The immune system responds by producing antibodies called Immunoglobulin E (IgE). These antibodies are specific to the peanut allergen.

  4. Release of Histamines: The IgE antibodies bind to immune cells called mast cells and basophils. When the peanut allergen enters the body again, it binds to the IgE antibodies on these cells, triggering them to release chemicals like histamine.

  5. Allergic Reaction: The release of these chemicals causes an allergic reaction. This can result in various symptoms such as itching, hives, swelling, difficulty breathing, and in severe cases, anaphylaxis.

  6. Memory: The immune system remembers this allergen. So, the next time Jorge eats a peanut, his immune system will react in the same way, often more quickly and severely.

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The first investigation of anti-IgE therapy for the management of FA was performed in a double-blind, randomized, dose-ranging (150, 300, or 450 mg of anti-IgE antibodies (TNX-901)) trial in 84 patients, 12 to 60 years of age, with a positive history of peanut allergy. Although the highest TNX-901 dose significantly improved clinical symptoms and increased the threshold dose for peanuts, 25% failed to develop a tolerance to peanuts, suggesting a wide treatment response variability [36]. A subsequent double-blinded, placebo-controlled study was started in children 6 years of age, but discontinued because of safety issues related to pre-omalizumab challenges [37]. An open-label study in 14 adults between 18 and 50 years of age showed a significant increase in the mean tolerated dose of peanut protein (from 80 mg to 5080 mg) after 6 months of omalizumab; however, the administration of antihistamines and epinephrine was required in 10 of the 14 enrolled subjects [38]. To increase the safety of immunotherapy and possibly enhance tolerance development, a combination of anti-IgE therapy and FA-AIT was investigated. Two small double-blind, placebo-controlled food challenge trials in patients (age, 7–25 years) with a peanut [39] or cow’s milk [40] allergy were conducted by using omalizumab in combination with rapid oral food desensitization. During a washout period, participants were generally treated with omalizumab for 2 to 5 months and subsequently continued on treatment until a maintenance dose of OIT was achieved. In the first study, 92% of patients tolerated the challenge, but 46% of children experienced moderate to severe adverse events [39]. In the second trial, 9 out of 11 patients were able to complete dose escalation and only 1.8% of subjects still showed reactions requiring epinephrine [40]. Subsequently, a phase one clinical trial was designed in 25 participants (median age 7 years) with multiple FA. Participants were receiving OIT for up to 5 allergens simultaneously with omalizumab. Anti-IgE therapy was administered for 8 weeks prior to and 8 weeks following the initiation of the OIT protocol. Adverse reactions were reported in 5.3% of subjects. Additionally, 94% of reactions were mild and only one subject experienced a severe reaction requiring epinephrine [23]. Following this, a phase one double-blind, placebo-controlled food challenges study, enrolling patients aged 4–15 years with multiple FA, confirmed that adjunctive omalizumab with OIT provided a safe and rapid desensitization with a lower median rate of adverse events (27% vs. 68%). Interestingly, no serious or severe adverse events were recorded [41].

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