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Food Allergies – The Battle Between Self vs. Nonself

Updated: Dec 2, 2023


Food allergies are defined as adverse immune responses to food proteins that result in typical clinical symptoms involving the dermatologic, respiratory, gastrointestinal, cardiovascular, and/or neurologic systems.


The concept of "self vs. nonself" is a fundamental principle in immunology. It refers to the immune system's ability to distinguish between the body's own cells and foreign entities. In the context of food allergies, this concept plays a crucial role in understanding why the immune system may react to certain foods as if they were harmful invaders. Here's how "self vs. nonself" relates to food allergies:


1. Recognition of Self vs. Nonself: The immune system has mechanisms to recognize self (the body's own cells and proteins) from nonself (foreign substances, such as pathogens and allergens). This recognition is critical for maintaining immune tolerance and preventing the immune system from attacking the body's own tissues.


2. Immune Tolerance: Immune tolerance is the state in which the immune system does not react to self-antigens, preventing autoimmune reactions. It allows the immune system to distinguish between harmless self-antigens and potentially harmful nonself-antigens.


3. Food Allergy Development: In food allergies, a breakdown in immune tolerance occurs. The immune system mistakenly recognizes specific proteins in certain foods (allergens) as nonself and harmful, triggering an allergic response. This recognition is due to the production of allergen-specific IgE antibodies, which are normally reserved for responding to true threats, such as pathogens.


4. IgE-Mediated Response: When a person with a food allergy is exposed to an allergenic food, their immune system produces IgE antibodies against specific allergen proteins. These IgE antibodies sensitize mast cells and basophils, which are effector cells. Upon reexposure to the allergen, the immune system reacts as if it is defending against a foreign invader, resulting in an allergic reaction.


5. Loss of Immune Tolerance: The loss of immune tolerance to food allergens means that the body's immune system incorrectly identifies certain food proteins as nonself, leading to the production of IgE antibodies and allergic reactions.


Food allergies result from a breakdown in the immune system's ability to distinguish between self and nonself. The immune system erroneously identifies certain food proteins as nonself and triggers an allergic response, leading to symptoms. This loss of tolerance is central to the development and expression of food allergies.


IgE-mediated food allergies, also known as type I hypersensitivity reactions, are immune responses triggered by the presence of specific proteins in certain foods such as milk, egg, wheat or nuts. These immune responses involve the activation of immunoglobulin E (IgE) antibodies, which recognize and bind to the allergenic proteins. This binding, in turn, leads to the release of various inflammatory mediators, causing allergic symptoms that can range from mild to severe.


IgE-mediated food-allergic disease differs from non-IgE-mediated disease because the pathophysiology results from activation of the immune system, causing a T helper 2 response which results in IgE binding to Fcε receptors on effector cells like mast cells and basophils. The activation of these cells causes release of histamine and other preformed mediators, and rapid symptom onset, in contrast with non-IgE-mediated food allergy which is more delayed in onset.


Here's an overview of IgE-mediated food allergies:


Key Points:


IgE Antibodies: Immunoglobulin E (IgE) is a class of antibodies produced by the immune system in response to allergens. In the context of food allergies, IgE antibodies are specific to particular proteins found in certain foods.


Allergenic Proteins: Food allergies are triggered by specific proteins in foods. Common allergenic foods include peanuts, tree nuts, milk, eggs, soy, wheat, fish, and shellfish. These proteins are recognized by the immune system as foreign invaders, leading to an immune response.


Allergic Reaction: When an individual with IgE-mediated food allergies consumes a food containing allergenic proteins, the IgE antibodies bind to the proteins. This binding signals immune cells, such as mast cells and basophils, to release inflammatory mediators, including histamine.


Symptoms: The release of inflammatory mediators causes a range of allergic symptoms, which can affect different parts of the body. Common symptoms include hives, itching, swelling, digestive issues, respiratory problems, and, in severe cases, anaphylaxis.


Anaphylaxis: Anaphylaxis is a severe and potentially life-threatening allergic reaction that can occur rapidly after allergen exposure. It involves a systemic response, causing difficulty breathing, a drop in blood pressure, and other severe symptoms.


The Role of Mast Cells in Food Allergies


Mast cells play a central and pivotal role in the development and expression of food allergies. They are key effector cells in the allergic response to food allergens. Here's an overview of the role of mast cells in food allergies:


1. Allergen Recognition: Mast cells express high-affinity IgE receptors (FcεRI) on their surface. When an individual with a food allergy is exposed to a specific allergen, the immune system produces allergen-specific IgE antibodies. These IgE antibodies bind to FcεRI on mast cells and sensitize them to that particular allergen.


2. Degranulation: Upon re-exposure to the same allergen, the allergen binds to IgE antibodies on the mast cell surface. This binding triggers a rapid and massive release of inflammatory mediators from the mast cell's granules. Histamine is one of the primary mediators released, and it plays a major role in the immediate allergic response.


3. Inflammatory Mediators: In addition to histamine, mast cells release other pro-inflammatory mediators, including leukotrienes, prostaglandins, and cytokines. These mediators are responsible for the hallmark symptoms of an allergic reaction, such as itching, swelling, hives, and gastrointestinal symptoms.


4. Eosinophil Activation: Mast cell-derived mediators also promote the activation and recruitment of eosinophils, another type of white blood cell. Eosinophils are commonly found in allergic inflammation and play a role in the prolonged allergic response seen in food allergies.


5. Gastrointestinal and Skin Symptoms: In food allergies, mast cell degranulation can lead to gastrointestinal symptoms, such as abdominal pain, diarrhea, and vomiting. Skin symptoms, such as itching and hives, are also common in food allergies.


6. Anaphylaxis: In severe cases of food allergies, mast cell degranulation can lead to anaphylaxis, a life-threatening allergic reaction characterized by a rapid drop in blood pressure, difficulty breathing, and systemic symptoms.


7. Chronic Inflammation: Repeated exposure to food allergens can result in chronic inflammation in the gastrointestinal tract, leading to conditions like eosinophilic esophagitis and eosinophilic gastritis.


8. Target for Allergy Therapies: Due to their central role in allergic reactions, mast cells are the target of various allergy therapies. Anti-allergy medications, such as antihistamines and epinephrine, work to counteract the effects of mast cell degranulation.


Understanding the role of mast cells in food allergies is essential for the development of allergy management and treatment strategies.


The Role of KIT Proto-Oncogene in Mast Cells and Food Allergies


The KIT proto-oncogene, also known as CD117, is a receptor tyrosine kinase (RTK) that is predominantly expressed on the surface of mast cells. It plays a crucial role in mast cell development, activation, and survival. While the KIT proto-oncogene is primarily associated with mast cell biology, its role in the context of food allergies is not as well-documented as its role in other mast cell-related conditions, such as mastocytosis. However, research has shed light on its potential relevance in food allergies. Here's an overview of the role of the KIT proto-oncogene in mast cells and food allergies:


1. Mast Cell Development: KIT is essential for the development and differentiation of mast cells from their progenitor cells in the bone marrow. KIT activation by its ligand, stem cell factor (SCF), is crucial for mast cell maturation.


2. Mast Cell Activation: KIT activation is involved in mast cell activation and degranulation. Crosslinking of KIT by SCF or other ligands triggers intracellular signaling pathways that lead to the release of histamine and other mediators from mast cell granules.


3. Influence on Allergic Responses: Mast cells are central to allergic responses, including food allergies. KIT activation and signaling can potentiate the allergic response by promoting mast cell activation and mediator release in the presence of allergenic food proteins.


4. Mast Cell Proliferation: In conditions like mastocytosis, a disorder characterized by an abnormal proliferation of mast cells, malfunctions in the KIT gene are common. These malfunctions lead to constitutive activation of KIT and uncontrolled mast cell growth.


5. Potential Relevance in Food Allergies: While research specific to KIT in food allergies is limited, understanding its role in mast cell biology is crucial, as mast cells are key effector cells in food allergic reactions. Dysregulation of KIT activation in mast cells may contribute to the severity of allergic responses to food allergens.


6. Treatment Implications: In cases of mastocytosis or systemic mast cell disorders, targeted therapies aimed at inhibiting KIT activation and signaling are used to manage symptoms and prevent mast cell degranulation. The potential therapeutic targeting of KIT in the context of food allergies remains an area of ongoing research.


Here are some natural options that may influence KIT & KITLG (Mast Cell Growth Factor): [R, R]


· ATP (D-Ribose)

· Adenosine (Cordyceps)

· Vitamin A (Liver Extract)

· Thymidine (Cordyceps sinensis, Aloe vera) [R]

· Agarose (Red Marine Algae)

· Inositol

· Genistein (Glycine max)

· Creatine

· Butyrate (Inulin FOS)

· Polysaccharides

· Uridine/Uracil/ Pyrimidine (Panax ginseng, Cordyceps, Aloe vera, Triticum aestivum (wheat) [R]


The Role of Histamine in Food Allergies


Histamine is a biologically active compound that plays a central role in the development and expression of food allergies. It is released by mast cells and basophils during an allergic response and is responsible for many of the hallmark symptoms associated with food allergies. Here's an overview of the role of histamine in food allergies:


1. Mast Cell and Basophil Activation: In food allergies, the initial exposure to an allergenic protein results in the activation of sensitized mast cells and basophils. These cells contain granules filled with histamine.


2. Degranulation: Upon re-exposure to the same allergen, allergen-specific IgE antibodies on mast cells and basophils bind to the allergen. This binding triggers a rapid degranulation of these cells, releasing histamine and other inflammatory mediators.


3. Immediate Allergic Response: Histamine is a primary mediator of the immediate allergic response. It is responsible for the sudden onset of symptoms such as itching, hives, swelling (angioedema), and redness of the skin.


4. Vasodilation: Histamine causes blood vessels to dilate (expand), leading to increased blood flow to the affected area. This contributes to the redness and warmth observed during an allergic reaction.


5. Increased Vascular Permeability: Histamine increases the permeability of blood vessel walls, allowing fluid and immune cells to escape into the surrounding tissue. This results in swelling and the formation of hives.


6. Bronchoconstriction: In some food allergies, particularly those involving respiratory symptoms, histamine can cause bronchoconstriction (narrowing of the airways). This can lead to breathing difficulties, wheezing, and coughing.


7. Gastrointestinal Symptoms: Histamine also plays a role in gastrointestinal symptoms associated with food allergies, including abdominal pain, diarrhea, and vomiting.


8. Target for Allergy Medications: Antihistamines are commonly used to mitigate the effects of histamine during allergic reactions. They work by blocking histamine receptors (H1 receptors) on target cells, reducing the severity of symptoms.


9. Delayed Allergic Response: While histamine is primarily associated with the immediate allergic response, it can also contribute to prolonged allergic inflammation when it leads to the recruitment of other immune cells, such as eosinophils.


Understanding the role of histamine in food allergies is essential for both the diagnosis and management of these conditions. Antihistamines are frequently used to alleviate the symptoms of food allergies, particularly in cases where histamine release is a significant contributor to the allergic response.


Here are some natural options that may influence Histamine Receptor H1, Histamine Receptor H2, Histamine Receptor H3, Histamine Receptor H4, and Histamine N-Methyltransferase [R, R, R, R, R]


· Inositol

· Thymidine (Cordyceps sinensis, Aloe vera) [R]

· Creatine

· ATP (D-Ribose)

· Acetylcholine (Sunflower Lecithin)

· Guanidine/Guanine (Panax ginseng, Glycine max) [R]

· NADPH/CoQ10 (Liver Extract, Beets)

· Sodium Bicarbonate

· Calcium


Other Histamine Compounds:


· Quercetin (Sophora japonica) [R]

· Vitamin C [R]

· Astragalus [R]

· Kaempferol [R]

· Fisetin (Strawberry) [R]

· Rutin (Sophora japonica) [R]

· Black tea [R]

· Curcumin [R]

· Chinese Skullcap [R]


The Role of Leukotrienes in Food Allergies


Leukotrienes are lipid mediators that play a significant role in the development and expression of food allergies. They are produced by various immune cells, particularly mast cells and eosinophils, and are involved in the allergic response to food allergens. Here's an overview of the role of leukotrienes in food allergies:


1. Mast Cell Activation: When an individual with a food allergy is exposed to a specific allergen, allergen-specific IgE antibodies bind to FcεRI receptors on mast cells. This binding triggers mast cell degranulation, leading to the release of histamine and other mediators, including leukotrienes.


2. Leukotriene Production: Mast cells and eosinophils, among other immune cells, produce leukotrienes in response to allergen exposure. These lipid mediators are synthesized from arachidonic acid through the action of enzymes, including 5-lipoxygenase (5-LO).


3. Inflammatory Mediators: Leukotrienes are potent inflammatory mediators that contribute to the allergic response. They are involved in several aspects of the allergic reaction, including inflammation, bronchoconstriction, and increased vascular permeability.


4. Bronchoconstriction: Leukotrienes are known for their role in causing bronchoconstriction, which leads to breathing difficulties, wheezing, and coughing, especially in individuals with respiratory symptoms in response to food allergens.


5. Increased Vascular Permeability: Leukotrienes contribute to the increased permeability of blood vessel walls, allowing fluid and immune cells to move into the surrounding tissue. This process results in swelling, redness, and the formation of hives.


6. Protracted Inflammation: Leukotrienes can promote a protracted inflammatory response by recruiting other immune cells, such as eosinophils. Eosinophils release additional pro-inflammatory molecules, leading to chronic inflammation.


7. Target for Allergy Medications: Leukotriene modifiers, including leukotriene receptor antagonists and 5-lipoxygenase inhibitors are used to alleviate the effects of leukotrienes in food allergies. These work by blocking leukotriene receptors or inhibiting the synthesis of leukotrienes.


8. Gastrointestinal Symptoms: Leukotrienes also contribute to gastrointestinal symptoms, such as abdominal pain and diarrhea, which are common in food allergies.


Understanding the role of leukotrienes in food allergies is essential for the diagnosis and management of these conditions. Leukotriene modifiers are part of the treatment strategy for individuals with food allergies, particularly those with symptoms related to respiratory and gastrointestinal systems.


Here are some natural options that may influence Leukotrienes: [R]


· Baicalein (Skullcap)

· Omega-3 fatty acid (Flax)

· Linoleic acid (Flax)

· Silibinin (Milk thistle)

· Resveratrol (Japanese knotweed)

· Soy Bean (Glycine max, Nattokinase)

· Curcumin

· Vitamin C (Acerola)

· Eugenol (Cinnamon)

· Ursolic acid (Prunella vulgaris/Heal all, Apple)

· Quercetin (Sophora japonica)

· Genistein (Glycine max)

Other Arachidonate 5-lipoxygenase (5-LOX) Compounds:


· Sulforaphane (Broccoli sprouts) (R)

· Indole-3-carbinol (Broccoli sprouts) (R)

· Phosphatidylcholine (Sunflower Lecithin) (R)

· Berberine (R)

· Fisetin (Strawberry) (R)

· Ellagic acid – Pomagranite, Raspberry (R)


Other Leukotriene Compounds:


· Panax ginseng [R]

· Withania somnifera (Ashwagandha) [R]

· Propolis [R]

· Aloe vera [R]

· Ginger [R]


The Role of Prostaglandin Cyclooxygenase-2 (COX-2) in Food Allergies


Cyclooxygenase-2 (COX-2) is an enzyme that plays a role in the inflammatory response and is involved in the development and expression of food allergies. COX-2 is responsible for the production of prostaglandins, lipid mediators that contribute to the inflammatory and allergic responses. Here's an overview of the role of COX-2 and prostaglandins in food allergies:


1. Allergen Exposure: When an individual with a food allergy is exposed to a specific allergen, it can trigger an immune response, including the activation of immune cells and the release of inflammatory mediators.


2. Prostaglandin Production: COX-2 is an enzyme that is induced during inflammation. It catalyzes the conversion of arachidonic acid into prostaglandins, particularly prostaglandin E2 (PGE2).


3. Inflammatory Mediators: Prostaglandins, including PGE2, are pro-inflammatory mediators that contribute to the inflammatory response in food allergies. They play a role in promoting inflammation, pain, fever, and vascular changes.


4. Vasodilation: Prostaglandins cause blood vessels to dilate, leading to increased blood flow to the affected area. This contributes to the redness and warmth observed during an allergic reaction.


5. Increased Vascular Permeability: Prostaglandins increase the permeability of blood vessel walls, allowing fluid and immune cells to escape into the surrounding tissue. This results in swelling and the formation of hives.


6. Bronchoconstriction: Prostaglandins, particularly PGE2, can cause bronchoconstriction (narrowing of the airways), which leads to breathing difficulties, wheezing, and coughing, especially in individuals with respiratory symptoms related to food allergies.


7. Gastrointestinal Symptoms: Prostaglandins also contribute to gastrointestinal symptoms, such as abdominal pain and diarrhea, which are common in food allergies.


8. Target for Allergy Medications: Compounds which inhibit COX-2 and prostaglandin production, can sometimes alleviate symptoms of food allergies, particularly those related to pain, fever, and inflammation.


9. Treatment Implications: Understanding the role of COX-2 and prostaglandins in food allergies is essential for the management of these conditions. In some cases, anti-inflammatory compounds that target COX-2 may be considered to manage symptoms.


Here are some natural options that may influence COX-2: [R]


· Curcumin

· Omega-3 fatty acid (Flax)

· Hesperidin (Lemon Citrus Peel)

· Ursolic acid (Prunella vulgaris/Heal all, Apple)

· Rosmarinic acid (Prunella vulgaris/Heal all)

· Resveratrol (Japanese knotweed)

· Panex Ginseng

· 6-Shogaol (Ginger)

· 8-Gingerol (Ginger)

· 8,11,14-Eicosatriynoic Acid (Pomegranate)

· Quercetin (Sophora japonica)

· Wogonin (Skullcap)

· Scutellaria (Skullcap)

· Chenodeoxycholic acid (TUDCA)

· Silibinin (Milk thistle)

· Genistein (Glycine max)

· Sulforaphane (Broccoli sprouts)

· Nobiletin (Lemon Citrus Peel)


Other COX2 Modulators:


· Danshen (R)

· Butyrate (Inulin FOS) (R)

· Cinnamon (R)

· Aloe vera (R)

· Astragalus (R)

· Pycnogenol (R)

· Glucosamine (R, R)

· Spirulina (R)

· Berberine (R)

· Chrysin (Propolis) (R)

· Anthocyanins (from red raspberries) (R)

· Emodin (Japanese knotweed) (R)


The Role of Fc receptors in IgE-mediated Food Allergies


The role of Fc receptors in IgE-mediated food allergies is crucial in understanding how these allergic reactions occur. Fc receptors, or FcRs, are cell surface receptors found on various immune cells, and they play a central role in mediating the immune response to IgE antibodies.


These receptors are essential for various immune responses, including phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), and the regulation of immune cell activity. While the modulation of FcRs typically involves drugs or antibodies, some natural compounds may indirectly influence FcRs by modulating the immune system.


Here are a few natural compounds and substances that may have an impact on FcRs:


Curcumin: Curcumin is a bioactive compound found in turmeric with anti-inflammatory and immunomodulatory properties. It may influence the activity of immune cells, potentially affecting FcRs' function.


Ginseng: Ginseng is an adaptogenic herb with potential immunomodulatory effects. It has been studied for its ability to influence immune cell activity, which could indirectly impact FcRs.


Astragalus: Astragalus is an herb known for its immune-enhancing properties. It may help regulate immune responses, potentially affecting the activation of immune cells through FcRs.


Resveratrol: Resveratrol is a natural polyphenol found in grapes, red wine, and Japanese knotweed. It has antioxidant and anti-inflammatory properties and may influence immune cell activity and immune response, potentially affecting FcRs.


Omega-3 Fatty Acids: Omega-3 fatty acids, found in fish oil and flax, have anti-inflammatory properties and can modulate immune responses. These fatty acids may indirectly influence FcRs by altering the immune system's behavior.


Prebiotics: Prebiotics, which help feed beneficial gut bacteria, can regulate immune responses and influence immune cell activity. This may have an indirect effect on FcRs.


Beta-Glucans: Beta-glucans are polysaccharides found in the cell walls of certain fungi, such as mushrooms. They can stimulate immune responses and modulate the activity of immune cells, potentially affecting FcRs.


Other natural compounds may help modulate the immune response and potentially influence the production of immunoglobulin E (IgE), indirectly affecting allergic responses.


Here are some herbs and natural compounds that have been studied for their potential immunomodulatory effects:


Quercetin: Quercetin is a flavonoid found in Sophora japonica. It has antioxidant and anti-inflammatory properties and may help stabilize mast cells, reducing the release of histamine and other allergic mediators.


Spirulina: Spirulina is a type of blue-green algae known for its potential immune-modulating effects. It may help regulate the immune response, reducing allergy symptoms.


Turmeric (Curcumin): Curcumin is the active compound in turmeric with anti-inflammatory properties. It may help reduce the production of pro-inflammatory cytokines associated with allergic responses.


Ginger: Ginger has anti-inflammatory properties and may help alleviate symptoms of allergies and asthma by reducing inflammation in the airways.


Astragalus: Astragalus is an herb known for its immune-boosting properties. It may help strengthen the immune system and support overall immune health.


The Role Interleukins and JAK/STAT Signaling in Food Allergies


Interleukins (ILs) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway are central components of the immune response and play critical roles in the development and regulation of various allergic conditions, including food allergies. Here is an overview of how interleukins and the JAK/STAT pathway are involved in food allergies:


Interleukins (ILs) in Food Allergies:


IL-4 and IL-13: IL-4 and IL-13 are key cytokines involved in food allergies. They are primarily produced by T-helper type 2 (Th2) cells and promote the production of immunoglobulin E (IgE) antibodies. IgE antibodies are central to the allergic response and are responsible for the immediate hypersensitivity reactions seen in food allergies.


· IL-4 Compounds: [R]


· 3,4-Dihydroxycinnamic Acid/Caffeic acid (Ceylon cinnamon, Star anise)

· Guanidine/Guanine (Panax ginseng, Glycine max) [R]

· Astragalus [R]

· Licorice [R]

· Emodin (Japanese knotweed) [R]

· Skullcap [R]

· Propolis [R]



· IL-13 Compounds: [R]


· Mannose

· Polysaccharide

· Fisetin (Strawberry)

· Acetylcholine (Sunflower Lecithin)

· Hyaluronic acid (Deer Antler Velvet)

· Thymidine (Cordyceps sinensis, Aloe vera) [R]

· Inositol

· Vitamin A

· Emodin (Japanese knotweed) [R]

· Licorice [R]

· Astragalus [R]


IL-5: IL-5 is involved in the activation and recruitment of eosinophils, a type of white blood cell. Elevated levels of IL-5 are associated with eosinophilic conditions such as eosinophilic esophagitis and contribute to allergic inflammation in food allergies.


· IL-5 Compounds: [R]


· Glucosamine (Deer Antler Velvet)

· Genistein (Glycine max)

· Thymidine (Cordyceps sinensis, Aloe vera) [R]

· Agar (Red Marine Algae)

· Butyrate (Inulin FOS)

· Dextran sulfate (Algae)


IL-9: IL-9 can enhance the immune response in food allergies by promoting mast cell activation and histamine release, which leads to allergic symptoms such as itching and swelling.


· IL-9 Compounds: [R]

· Vitamin A

· Genistein (Glycine max)

· Thymidine (Cordyceps sinensis, Aloe vera) [R]


IL-10: IL-10 is an anti-inflammatory cytokine that plays a regulatory role in the immune system. It can help control excessive inflammation seen in allergic reactions.


· IL-9 Compounds: [R]

· Quercetin (Sophora japonica)

· Guanine (Panax ginseng, Glycine max (soybean)) [R]

· Thymidine (Cordyceps sinensis, Aloe vera) [R]


The Role of Th2 Cytokine-Mediated Immunity and Inflammation in Food Allergies


Th2 cytokine-mediated immunity and inflammation play a pivotal role in the development and expression of food allergies. Food allergies are characterized by an inappropriate and hypersensitive immune response to harmless food proteins. Th2 cytokines, a subset of T-helper lymphocytes' immune response, orchestrate the immune response in food allergies. Here's an overview of the role of Th2 cytokine-mediated immunity and inflammation in food allergies:


1. Activation of Th2 Response: In food allergies, the immune system shifts toward a Th2-dominant immune response. This involves the activation of Th2 lymphocytes, which secrete various cytokines, including interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13).


2. IgE Production: IL-4 is a key Th2 cytokine that promotes the production of allergen-specific IgE antibodies. IgE antibodies are responsible for the immediate hypersensitivity response seen in food allergies.


3. Mast Cell Activation: Once allergen-specific IgE antibodies bind to high-affinity IgE receptors (FcεRI) on the surface of mast cells and basophils, they become sensitized. Subsequent exposure to the allergen leads to mast cell activation, degranulation, and the release of histamine and other inflammatory mediators.


4. Eosinophil Recruitment: IL-5 is a Th2 cytokine that plays a central role in the activation and recruitment of eosinophils, a type of white blood cell. Eosinophils are involved in the allergic inflammation seen in food allergies.

5. Gastrointestinal and Cutaneous Symptoms: Th2 cytokines, particularly IL-13, contribute to the development of gastrointestinal symptoms, such as vomiting, diarrhea, and abdominal pain, commonly seen in food allergies. IL-4 and IL-13 can also lead to skin symptoms, including itching and hives.


6. Airway Inflammation: In some cases, food allergies can lead to respiratory symptoms. Th2 cytokines can contribute to airway inflammation and may exacerbate conditions such as asthma in individuals with coexisting food allergies.


7. Chronic Allergic Responses: Prolonged exposure to food allergens can result in chronic inflammation, leading to conditions like eosinophilic esophagitis and eosinophilic gastritis, which are characterized by significant Th2-mediated inflammation.


8. Potential Therapeutic Targets: Understanding the role of Th2 cytokine-mediated inflammation in food allergies has led to the development of targeted therapies, including biologics that block specific Th2 cytokines, such as IL-4 and IL-13. These treatments aim to modulate the immune response and alleviate allergic symptoms.


In summary, Th2 cytokine-mediated immunity and inflammation are central to the pathophysiology of food allergies. Their activation leads to the production of allergen-specific IgE antibodies, mast cell activation, eosinophil recruitment, and the release of pro-inflammatory molecules, all of which contribute to the development of allergic symptoms. Research into the role of Th2 cytokines has opened new avenues for potential therapeutic interventions in food allergies.


The Role of Thymic Stromal Lymphopoietin (TSLP) in Food Allergies


Thymic Stromal Lymphopoietin (TSLP) is a cytokine that plays a significant role in the development and regulation of immune responses, including those involved in food allergies. TSLP is primarily produced by epithelial cells at barrier surfaces, such as the skin and gastrointestinal tract, and it influences the immune system's response to allergens. Here's an overview of the role of TSLP in food allergies:


1. Barrier Function: TSLP is produced by epithelial cells in response to various environmental triggers, including allergens. It serves as a sentinel at the body's barrier surfaces and plays a role in maintaining the integrity of these barriers.


2. Immune Cell Activation: TSLP acts on various immune cells, including dendritic cells, T cells, and B cells. It promotes the activation and differentiation of these immune cells, particularly in a Th2-skewed manner.


3. Th2 Immune Response: TSLP is known for its ability to skew the immune response toward a Th2-dominant profile. This includes the production of Th2 cytokines such as interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13), which are associated with allergic responses.


4. Dendritic Cell Maturation: TSLP influences dendritic cell maturation and function. Dendritic cells exposed to TSLP can promote the activation of naive T cells and facilitate the development of allergic sensitization.


5. IgE Production: TSLP can enhance the production of allergen-specific IgE antibodies, which are central to the allergic response seen in food allergies.


6. Mucosal Inflammation: TSLP can contribute to mucosal inflammation and the development of gastrointestinal symptoms in food allergies. It plays a role in the activation and recruitment of eosinophils and other inflammatory cells.


7. Potential Therapeutic Target: Due to its role in promoting allergic responses, TSLP has been investigated as a potential therapeutic target in allergic diseases, including food allergies. Inhibiting TSLP activity is a strategy aimed at reducing the severity of allergic reactions.


TSLP's role in food allergies is complex and involves the activation of various immune cells and cytokines. Research into the specific mechanisms by which TSLP influences food allergies is ongoing. Understanding TSLP's contribution to the allergic response is essential for the development of targeted therapies and interventions for individuals with food allergies.


Natural Compounds and Herbs for Thymic Stromal Lymphopoietin (TSLP)


Thymic stromal lymphopoietin (TSLP) is an interleukin 7 (IL-7)-like cytokine originally characterized by its ability to promote the activation of B cells and dendritic cells (DCs).


Src Family Kinase Inhibitors & Hsp90 Inhibitors are mentioned to effectively target the expression of IL-7 and TSLP.


Here are some natural options that may influence SRC Kinase: [R]


· Vitamin C

· Kaempherol (Broccoli sprouts, Apple, Raspberries, Aloe vera, Glycine max (soy), Elderberry, Ginger, Goji berry) [R]

· Adenosine (Cordyceps)

· Scutellarein (Skullcap)

· Hesperadin (Lemon Citrus Peel)

· Acetylcholine (Sunflower Lecithin)

· Curcumin

· Inositol

· Guanidine/Guanine (Panax ginseng, Glycine max) [R]

· Genistein (Glycine max)

· Resveratrol (Japanese knotweed)

· Agar (Red Marine Algae)


Here are some natural options that may influence Heat Shock Protein 90: [R]


· Quercetin (Sophora japonica)

· Silibinin (Milk thistle)

· Curcumin

· Vitamin A

· Genistein (Glycine max)

· ATP (D-Ribose)

· Adenosine (Cordyceps)

· Inositol

· Withaferin A (Ashwagandha) [R]


JAK/STAT Signaling in Food Allergies


JAK/STAT Pathway: The JAK/STAT pathway is a signaling cascade that transmits signals from the cell surface, through the cytoplasm, and into the cell nucleus to regulate gene expression. It is crucial for the transmission of signals from various cytokine receptors, including those for IL-4 and IL-13.


JAK Inhibition: In recent years, natural compounds targeting the JAK/STAT pathway have been discovered for the potential mitigation of allergic diseases, including food allergies. In particular, JAK inhibitors can block the signaling of various cytokines, reducing the inflammatory response associated with allergic conditions.


Potential Therapeutic Target: The JAK/STAT pathway is considered a potential therapeutic target in the treatment of allergic diseases, as it can modulate the immune response, reducing the effects of pro-inflammatory cytokines involved in food allergies.


Overall, interleukins and the JAK/STAT pathway are central to the development and regulation of immune responses in food allergies. Understanding the specific roles of these signaling molecules and pathways is crucial for the development of targeted therapies and potential remedies for food allergy management.


Natural Compounds and Herbs for JAK/STAT Inhibition


Here are some natural options that may influence JAK/STAT signaling:


· Betulinic acid (Chaga/Birch bark/Heal all) (R)

· Olive oil (R)

· Resveratrol (Japanese knotweed) (R)

· Emodin (Japanese knotweed) (R)

· Quercetin (R)

· Broccoli sprouts (R)

· Ginger (R)

· Fucoidan (Bladderwrack) (R)

· Mushroom (R)

· Milk Thistle (R)

· Berberine (R)

· Glucosamine (R)

· Butyrate (Inulin FOS) (R)

· Piceatannol (R)

· Curcumin (R)

· Genistein (Glycine max) (R)

· ATP (D-Ribose) (R)

· Lysine (R)

· Ornithine (R)

· Inositol (R)

· CoQ10 (Beets/Liver Extract) (R)


The Role of Mannose Binding Lectin in Food Allergies


Mannose binding lectin (MBL) is a protein involved in the innate immune system and plays a role in recognizing and binding to sugar molecules (mannose) on the surface of pathogens, including bacteria, viruses, and fungi. While its primary function is to initiate immune responses against infectious agents, research has also explored the potential role of MBL in food allergies. Here's an overview of the role of MBL in food allergies:


1. Innate Immunity: MBL is a component of the innate immune system, which provides the first line of defense against pathogens. It recognizes and binds to specific patterns on the surfaces of pathogens, including those found in food.


2. Allergen Recognition: MBL has the ability to bind to certain food allergens. This interaction can facilitate the clearance of allergens from the body and may play a role in the immune response to allergenic proteins in food.


3. Immunomodulatory Effects: MBL can modulate the immune response by influencing the balance between pro-inflammatory and anti-inflammatory responses. Its interactions with allergens in the digestive tract may affect the development of food allergies.


4. Associations with Food Allergies: Some studies have suggested that deficiencies or genetic variations in MBL may be associated with an increased risk of developing food allergies, especially in infants and young children. A deficiency in MBL could potentially impact the body's ability to clear allergens from the gastrointestinal tract and influence the development of allergic reactions.


Natural Compounds and Herbs for MBL


Here are some natural options that may influence MBL: [R]


· Mannose

· Fucose (Bladderwrack)

· Glucosamine (Deer Antler Velvet)

· Beta glucan

· Galactose (White mulberry, Flax, Beets, Sunflower, Licorice, Cherry, Ginger, Fig, Olive) [R]

· Lecithin

· Maltose

· Amylose

· ATP (D-Ribose)

· Agarose (Red Marine Algae)

· Polysaccharides

· Monosaccharides


The Role of Spleen Tyrosine Kinase in Food Allergies


Spleen Tyrosine Kinase (Syk) is an enzyme that plays a significant role in immune cell signaling and allergic responses. Here's an overview of the potential role of Syk in food allergies:


1. Mast Cell and Basophil Activation: Syk is a key mediator in signaling pathways that lead to the activation of mast cells and basophils, two types of immune cells central to allergic responses. When these cells are activated in response to an allergen, they release histamine and other inflammatory mediators, leading to allergic symptoms.


2. IgE-Mediated Allergic Reactions: In IgE-mediated allergic reactions, allergen-specific IgE antibodies bind to high-affinity IgE receptors (FcεRI) on the surface of mast cells and basophils. This binding activates Syk, leading to the release of histamine and other inflammatory molecules.


3. Potential Contribution to Food Allergies: While Syk's role in allergic responses is well-established, its specific role in food allergies is still being elucidated. Research suggests that it may play a role in mediating allergic reactions to food allergens, especially those involving mast cell and basophil activation.


4. Pharmacological Inhibition: Syk inhibitors have been developed for various allergic conditions, such as asthma and allergic rhinitis. While these inhibitors are not yet widely used for food allergies, they may hold promise as potential treatments to mitigate allergic responses to food allergens.


5. Immunomodulatory Potential: Modulating Syk activity may be a strategy to influence the severity of food allergies. This could involve the development of targeted therapies that block Syk activation and reduce the release of inflammatory mediators.


Natural Compounds and Herbs for SYK


Here are some natural options that may influence SYK: [R]


· Piceatannol

· Ellagic acid (Pomegranate, Raspberry)

· Inositol

· Genistein (Glycine max, Soy, Nattokinase)

· Adenosine (Cordyceps)

· Resveratrol (Japanese knotweed)

· ATP (D-Ribose)


The Role of Protein Tyrosine Phosphatase Non-Receptor Type 6 in Food Allergies


Protein Tyrosine Phosphatase Non-Receptor Type 6 (PTPN6), also known as SHP-1 (Src homology region 2 domain-containing phosphatase-1), is an intracellular enzyme that plays a significant role in immune cell signaling and immune system regulation. While it has been more extensively studied in the context of autoimmune diseases and immune responses to infections, its role in food allergies is not as well-documented. However, research is ongoing, and here is an overview of the potential role of PTPN6 in food allergies:


1. Immune Cell Signaling: PTPN6/SHP-1 is an intracellular phosphatase that negatively regulates immune cell signaling. It acts as a feedback mechanism to inhibit the activation of immune cells, including mast cells, basophils, and T cells.


2. Mast Cell and Basophil Regulation: PTPN6/SHP-1 can influence the activation and degranulation of mast cells and basophils, which are key players in allergic responses. Its activity can dampen the release of histamine and other inflammatory mediators, which are responsible for allergic symptoms.


3. Inhibition of Immune Responses: PTPN6/SHP-1 is involved in downregulating the signaling pathways that lead to immune responses. Dysregulation of PTPN6/SHP-1 activity can result in increased immune cell activation and a more robust immune response.


4. Potential Role in Food Allergies: While research on PTPN6/SHP-1 in food allergies is limited, there is interest in understanding how the enzyme may influence the development and regulation of allergic reactions to food allergens. Dysregulation of PTPN6/SHP-1 may contribute to the excessive immune response seen in food allergies.


5. Therapeutic Potential: Modulating PTPN6/SHP-1 activity is a potential strategy for influencing the severity of allergic reactions. This could involve the development of targeted therapies that enhance the enzyme's activity to limit immune cell activation in response to food allergens.


Natural Compounds and Herbs for PTPN6/SHP-1


Here are some natural options that may influence PTPN6/SHP-1: [R]


· Inositol

· Vitamin A

· NADPH/CoQ10 (Liver Extracts/Beets)

· Thymidine (Cordyceps sinensis, Aloe vera) [R]

· Adenosine (Cordyceps)

· Genistein (Glycine max)


The Role of Protein Tyrosine Phosphatase Non-Receptor Type 11 in Food Allergies


Protein Tyrosine Phosphatase Non-Receptor Type 11 (PTPN11), also known as SHP-2 (Src homology 2 domain-containing phosphatase-2), is an intracellular enzyme that is involved in various cellular signaling pathways, including those related to immune responses. While PTPN11 is more extensively studied in the context of cellular growth and development, its precise role in food allergies is not well-documented. However, research is ongoing, and here is an overview of the potential role of PTPN11 in food allergies:


1. Cell Signaling Regulation: PTPN11/SHP-2 is a phosphatase enzyme that plays a role in regulating cell signaling. It can influence the activation of signaling pathways downstream of cell surface receptors, including immune receptors.


2. Immune Cell Activation: PTPN11/SHP-2 is involved in the activation of immune cells, including T cells and B cells. It can influence the development and maintenance of immune responses.


3. Potential Role in Allergic Responses: While research on PTPN11/SHP-2 in the context of food allergies is limited, there is interest in understanding how the enzyme may contribute to the development and regulation of allergic reactions to food allergens.


4. Immunomodulation: Dysregulation of PTPN11/SHP-2 activity may contribute to an imbalance in immune responses, potentially leading to a heightened allergic response to food allergens.


5. Therapeutic Potential: Modulating PTPN11/SHP-2 activity may be explored as a potential strategy for influencing the severity of allergic reactions, although this area of research is in its early stages.


Natural Compounds and Herbs for PTPN11/SHP-2


Here are some natural options that may influence PTPN11/SHP-2: [R]


· Acetylcholine (Sunflower Lecithin)

· Inositol

· Lysine

· NADPH/CoQ10 (Liver Extracts/Beets)

· Thymidine (Cordyceps sinensis, Aloe vera) [R]

· Adenosine (Cordyceps)

· ATP (D-Ribose)

· Agar (Red Marine Algae)


The Role of SRC Kinase in Food Allergies


SRC kinase, also known as proto-oncogene tyrosine-protein kinase Src, is a non-receptor tyrosine kinase involved in various cellular signaling pathways. While SRC kinase is primarily associated with cancer and cell growth, it also has a role in immune cell signaling and has been explored in the context of allergic responses, including food allergies. Here's an overview of the potential role of SRC kinase in food allergies:


1. Immune Cell Signaling: SRC kinase is involved in intracellular signaling pathways in immune cells, including mast cells and basophils. These cells are central to allergic responses, including food allergies.


2. Mast Cell Activation: SRC kinase plays a role in the activation of mast cells. When allergens, such as food proteins, crosslink IgE antibodies on mast cells, SRC kinase is involved in the signaling cascade that leads to degranulation and the release of histamine and other inflammatory mediators.


3. Mediator of Allergic Symptoms: SRC kinase's involvement in the activation of mast cells contributes to the onset of allergic symptoms, including itching, swelling, and gastrointestinal discomfort, which are common in food allergies.


4. Potential Therapeutic Target: Due to its role in allergic reactions, SRC kinase has been explored as a potential therapeutic target in allergic diseases, including food allergies. Inhibiting SRC kinase activity could be a strategy to reduce allergic responses.


Natural Compounds and Herbs for SRC Kinase


Here are some natural options that may influence SRC Kinase: [R]


· Vitamin C

· Kaempherol (Broccoli sprouts, Apple, Raspberries, Aloe vera, Glycine max (soy), Elderberry, Ginger, Goji berry) [R]

· Adenosine (Cordyceps)

· Scutellarein (Skullcap)

· Hesperadin (Lemon Citrus Peel)

· Acetylcholine (Sunflower Lecithin)

· Curcumin

· Inositol

· Guanidine/Guanine (Panax ginseng, Glycine max) [R]

· Genistein (Glycine max)

· Resveratrol (Japanese knotweed)

· Agar (Red Marine Algae)


Summary


Food allergies are complex immune responses to specific food proteins. Various components of the immune system play integral roles in the development and expression of food allergies. Here's a summary of the key players in food allergies:


1. IgE Antibodies: Immunoglobulin E (IgE) antibodies are central to food allergies. They are produced in response to allergenic proteins and bind to immune cells, sensitizing them to the allergen.


2. Fc Receptors: Fc receptors on immune cells, such as mast cells and basophils, bind to IgE antibodies, triggering the release of inflammatory mediators when allergens crosslink IgE.


3. Mannose Binding Lectin (MBL): MBL is involved in the innate immune response. It can recognize allergenic proteins and contribute to their clearance.


4. Spleen Tyrosine Kinase (Syk): Syk is a signaling molecule involved in mast cell activation. It plays a critical role in IgE-mediated allergic reactions.


5. Mast Cells: Mast cells are effector cells in food allergies. They release histamine and other mediators when activated by allergen-IgE complexes.


6. Histamine: Histamine is a primary mediator of allergic symptoms, causing itching, swelling, and gastrointestinal distress.


7. Leukotrienes and Prostaglandins: These lipid mediators contribute to inflammation and bronchoconstriction, leading to respiratory and skin symptoms in food allergies.


8. Eosinophils: Eosinophils are white blood cells involved in allergic inflammation and are commonly elevated in food allergies.


9. KIT and KITLG: The KIT proto-oncogene is primarily expressed on mast cells and is involved in their development and activation. KITLG (stem cell factor) is its ligand.


10. JAK/STAT Signaling: This intracellular signaling pathway is implicated in the modulation of allergic responses and the expression of Th2 cytokines.


11. Interleukins: Th2 cytokines such as IL-4, IL-5, and IL-13 are pivotal in skewing the immune response toward allergies and influencing the production of IgE antibodies.


12. Th2 Cytokines: These cytokines orchestrate the immune response in food allergies, leading to the production of IgE antibodies and activation of effector cells.


13. SRC Kinase: SRC kinase is involved in immune cell signaling, including mast cells. It contributes to allergic reactions by promoting mast cell activation.


14. Heat Shock Protein 90: This molecular chaperone can influence the immune response and has been explored in the context of food allergies.


15. PTPN6 and PTPN11: Protein Tyrosine Phosphatase Non-Receptor Type 6 and Type 11 are signaling molecules involved in immune responses and are being studied in the context of food allergies.



These components interact in a complex manner, resulting in the development and expression of food allergies. Understanding their roles is crucial for the management and potential future remedy of food allergies.


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