Lymphatic Health

Dry brushing for lymphatic drainage and support

Med Establishment STUNNED By Brain Discovery THAT CHANGES EVERYTHING
Shalin Bhatt, a med student, discovered that there is a lymphatic connection with the brain (it was previously believed that there was no connection between the CNS and the lymphatic system).  This discovery shows us that NOT everything has been discovered by western medicine.  It also has implications for the function of the immune system and the gut-brain connection and much more.  

He calls his discovery the "Cerebrolymph Hypothesis" which he describes as an "anatomical framework for where CSF is produced".  CSF (cerebrospinal fluid) is produced in the deep brain region called the Choroid Plexus in the Ventricular System then it travels through the Subarachnoid Space (recently dubbed the Glymphatic System), then through the Meningeal Lymphatic Vessels into the last step (which is what he discovered) which is the Nerve-Adjacent Lymphatic Vessels Exiting Foramina.  This is where the fluid then enters the Peripheral Lymphatic System, the connection was not previously known.  This is essentially the "cleaning system" of the brain.  

This has implications for Alzheimer's research which has thus far focused on the proteins that build up in the brain, the Amyloid Plaques and and Tau Protein, but has not included the aspect of the dynamics of the cleaning process that would normally keep these proteins from building up in the first place.  This may lead to treatments that focus on repairing or maintaining the flow of lymph in the neck to treat or avoid Alzheimer's.  Shalin remarks that a lot of medical research is studying and validating traditional therapies (in this case acupuncture).  He mentions research showing benefits of acupuncture for Long COVID patients as well as Lymphedema and the associated brain fog.  Eastern medicine often considers the importance of flow in the body- could this be a concrete example?

This same researcher also published a theory recently called Glymphovasomotor Field Theory (GVF) which takes the idea that when a fluid moves (or circulates) that has ions in it, it creates an electromagnetic current, and applies it to the brain- if the CSF has ions in it and it moves through a structured flow pattern, maybe it creates an electromagnetic field- and maybe those fields effect neurons (which operate via electrical impulses).  This may have implications for consciousness.  

FOXP3 and Autoimmunity

 

The 2025 Nobel Prize in Medicine has been awarded for one of the most important discoveries in immunology: the biological system that keeps your immune system from turning on you.

Your immune cells are trained to destroy viruses, bacteria, and other foreign invaders. But that power has to be kept in check – or it can misfire, attacking your own organs. The process that prevents this is called peripheral immune tolerance, and it’s largely controlled by a type of cell called the regulatory T cell.

This year’s Nobel went to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for uncovering the genetic and cellular systems that make this immune self-regulation possible.

Back in 1995, Sakaguchi identified a previously unknown class of T cells that seemed to hold back the immune system from attacking the body. A few years later, Brunkow and Ramsdell discovered the gene that controlled them – FOXP3 – after studying a rare, fatal autoimmune disease in children. They found that when this gene is mutated, the immune system becomes unregulated and begins destroying healthy tissue.

Two years after that, Sakaguchi made the connection: FOXP3 was the master switch for the same immune-regulating cells he had identified earlier.

These discoveries launched a new field of research. Regulatory T cells are now being investigated in therapies to suppress autoimmunity, improve transplant success, and even enhance cancer treatment by modulating immune suppression around tumors.

Mast Cells Function as Sensors of Food Quality

IgE-Mast cell mediated allergy: a sensor of food quality
“allergic sensitization triggers the formation of avoidance behavior”, food can contain toxic noxious substances in different amounts and our bodies have ways of directly sensing it and responding to protect itself, including extra mucous production, nausea, vomiting, diarrhea, malabsorption, increased peristalsis.  These protective responses can be in response to our bodies sensing the toxicity via smell, taste, chemosensors in the gut.  This is a system that senses food quality and is more general and doesn’t adapt over time.

“Type 1 allergic reactions can induce similar symptoms as already known sensors of food quality. This similarity suggested that type 1 allergic reactions may also act as a ‘food quality control system” that allows learning and behaviour adaptation.³ The great advantage of involving the immune system would be its ability to recognize a nearly infinite number of distinct substances in a very specific manner, which is an original property of the adaptive immune system.” , “early type 1 allergic reactions trigger persistent allergen-specific avoidance behavior” , mice that were deficient in IgE and/or mast cells didn’t develop avoidance behavior.  “Type 1 allergic reactions promote protective antigen avoidance behaviour via IgE armed mast cells.”

“In response to allergic stimulation, cytokines from Tfh cells promote antibody class switch and antibody secretion by B cells, which yield antibodies of various isotypes, including IgE and IgG. IgE arms mast cells with an antigen-specific receptor.”, “during the early preclinical allergic response, mast cells are sufficiently activated to release leukotrienes, which triggers long-lasting allergen-specific avoidance behavior.”  If the exposure to the allergen persists IgE levels may increase and it increases its affinity to the allergen and “trigger strong mast cell activation and allergic disease.”

“In the absence of IgE or mast cells, allergen ingestion is increased, eventually leading to severe immunopathology.”

“IgE production is dependent on IL-4 from T follicular helper (Tfh) cells. This cytokine is sufficient to induce low affinity IgE, which however does not induce severe allergic symptoms, while additional cytokines from Tfh13 cells, including IL-13 and IL-21, are required for the development of high affinity IgE and anaphylaxis”

“High affinity IgE-mediated mast cell activation is the major mechanism for the induction of severe type-1 allergic reactions.” “murine IgG1 (human IgG4) antibodies which are also induced by IL-4, can trigger anaphylaxis too, though only in the presence of higher amounts of antigen” 

“Antibodies of the subclasses IgG2 and IgG3 are not IL-4 dependent, may not contribute to the pathology of type 1 allergic reactions, but can mediate severe inflammation via the activation of the complement system and various innate effector cells.”

“most allergic symptoms are absent in IgE deficient mice, even after forced uptake of high amounts of allergen, they still develop severe anaphylaxis, probably involving antibodies of other subclasses.”

“This work reveals a protective role of IgE-mediated mast cell activation, acting via modification of behavior.”

“even early allergic symptoms are associated with the activation of areas of the brain involved in the response to aversive stimuli.” 

“the induction of allergen avoidance behavior required only mild allergic reactions mediated by IgE, which precede the development of gut allergic inflammation. Evidence was provided, that activated mast cells affect behavior through the release of cysteinyl leukotrienes and the induction of growth and differentiation factor 15 by colonic epithelial cells, eventually sensed by the nervous system.”

“early IgE-mediated allergic reaction triggers avoidance behaviour while chronic allergen ingestion results in IgE-mediated disease.”

“The ratios between the levels of allergen specific IgE and the levels of allergen specific antibodies of other subclasses, correlate better with the development of severe allergic symptoms than the levels of IgE alone.”

“This reflects the fact that antibodies of other subclasses such as IgG1 or IgA can inhibit the severe allergic reactions induced by high-affinity IgE.”

“this mechanism may also be relevant in non-allergic individuals, who nevertheless produce subclinical quantities of IgE, potentially sufficient to cause mild mast cell activation and behavioural change, but without triggering allergic pathology.”

Immune sensing of food allergens promotes avoidance behaviour
https://www.nature.com/articles/s41586-023-06362-4

Mast cells link immune sensing to antigen-avoidance behaviour
https://www.nature.com/articles/s41586-023-06188-0

Food allergy as a biological food quality control system
https://www.cell.com/cell/fulltext/S0092-8674(20)31677-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867420316779%3Fshowall%3Dtrue

Identification of a T follicular helper cell subset that drives anaphylactic IgE
https://www.science.org/doi/10.1126/science.aaw6433

B-cell receptor physical properties affect relative IgG1 and IgE responses in mouse egg allergy
https://www.mucosalimmunology.org/article/S1933-0219(22)01761-5/fulltext

T follicular helper cells
https://www.immunology.org/public-information/bitesized-immunology/cells/t-follicular-helper-cells

Neuroinflammation

Neuroinflammation is inflammation of the brain, and is a basic finding in autism, ME/CFS, mast cell disease, and many other neurological disorders (or disorders with neurological symptoms).  Neuroinflammation can be difficult to recognize, test for, and treat.  Inflammation in general is a response of the immune system to try to protect and heal the body from threats (or perceived threats) such as infection or injury.  In the short term, inflammation is important as part of the healing process.  However, problems occur when the inflammation doesn't get turned off for some reason and becomes chronic.  Chronic inflammation is very hard on the body and is at the root of many diseases.  This article from the New Yorker called Inflamed provides a good place to start in learning more about inflammation in general.

What is neuroinflammation?  This is a short video by Dr Younger who is the director of The Pain and Fatigue Laboratory at UAB.  He says that neuroinflammation is essentially the same as inflammation elsewhere in the body, but because the immune system is different in the brain inflammation is expressed differently there.  Inflammation occurs when an injury or illness damages our tissues in some way- it is our body's way of alerting itself to an injury, illness, or threat and then coordinating the immune response to protect and heal itself.  Similarly, inflammation in the brain (from an illness or head injury for example) is also meant to heal the damaged tissues in the brain.  While inflamed tissues in the body tend to hurt, turn red, feel hot to the touch, and be visibly swollen, none of this is directly evident when the brain gets inflamed.  

We are not able to feel directly if our brains are inflamed, because there aren't the kind of pain receptors in the brain that we have elsewhere.  However, inflammation interferes with the functioning of the inflamed body part so there will be neurological symptoms from the neuroinflammation.  When we are very sick, with a bad flu for example, the way that we struggle to think clearly and function cognitively is one example of what neuroinflammation can look and feel like.

Neuroinflammation appears to be one of the central features in many neurological disorders, such as:

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis
" Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments."

Brain Inflammation A Hallmark Of Autism, Large-Scale Analysis Shows
"Previous studies had identified autism-associated abnormalities in cells that support neurons in the brain and spinal cord. In this study, Arking says, the research team was able to narrow in on a specific type of support cell known as a microglial cell, which polices the brain for pathogens and other threats. In the autism brains, the microglia appeared to be perpetually activated, with their genes for inflammation responses turned on. “This type of inflammation is not well understood, but it highlights the lack of current understanding about how innate immunity controls neural circuits,” says Andrew West, Ph.D., an associate professor of neurology at the University of Alabama at Birmingham who was involved in the study."

Neuroinflammation in Fibromyalgia and ME/CFS

Histamine regulation of microglia: Gene-environment interaction in the regulation of central nervous system inflammation.

Neuroinflammation, microglia and mast cells in the pathophysiology of neurocognitive disorders: a review
"Cells of the immune system and the central nervous system are capable of interacting with each other. The former cell populations respond to infection, tissue injury and trauma by releasing substances capable of provoking an inflammatory reaction. Inflammation is now recognized as a key feature in nervous system pathologies such as chronic pain, neurodegenerative diseases, stroke, spinal cord injury, and neuropsychiatric disorders such as anxiety/depression and schizophrenia. Neuroinflammation may also raise the brain's sensitivity to stress, thereby effecting stress-related neuropsychiatric disorders like anxiety or depression. The cytokine network plays a large part in how immune system cells influence the central nervous system. Further, inflammation resulting from activation of innate immune system cells in the periphery can impact on central nervous system behaviors, such as depression and cognitive performance. In this review, we will present the reader with the current state of knowledge which implicates both microglia and mast cells, two of the principle innate immune cell populations, in neuroinflammation. Further, we shall make the case that dysregulation of microglia and mast cells may impact cognitive performance and, even more importantly, how their cell-cell interactions can work to not only promote but also amplify neuroinflammation. Finally, we will use this information to provide a starting point to propose therapeutic approaches based upon naturally-occurring lipid signaling molecules. "

Microglia and mast cells: two tracks on the road to neuroinflammation
"One of the more important recent advances in neuroscience research is the understanding that there is extensive communication between the immune system and the central nervous system (CNS). Proinflammatory cytokines play a key role in this communication. The emerging realization is that glia and microglia, in particular, (which are the brain's resident macrophages), constitute an important source of inflammatory mediators and may have fundamental roles in CNS disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Microglia respond also to proinflammatory signals released from other non-neuronal cells, principally those of immune origin. Mast cells are of particular relevance in this context. These immunity-related cells, while resident in the CNS, are capable of migrating across the blood-spinal cord and blood-brain barriers in situations where the barrier is compromised as a result of CNS pathology. Emerging evidence suggests the possibility of mast cell-glia communications and opens exciting new perspectives for designing therapies to target neuroinflammation by differentially modulating the activation of non-neuronal cells normally controlling neuronal sensitization, both peripherally and centrally. This review aims to provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of microglia, neuroimmune interactions involving mast cells, in particular, and the possibility that mast cell-microglia crosstalk may contribute to the exacerbation of acute symptoms of chronic neurodegenerative disease and accelerate disease progression, as well as promote pain transmission pathways. We conclude by considering the therapeutic potential of treating systemic inflammation or blockade of signaling pathways from the periphery to the brain in such settings."

Mast cells and microglia and neuroinflammation

Allergy and Hypersensitivity Symptoms, Conditions, and DIseases

Allergy, Asthma & Immunology Glossary (from the AAAAI)
Video Library (from the AAAAI)
Allergy is an aspect of hypersensitivity, which is defined in Encyclopedia of Infection and Immunity as "Hypersensitivity as an immunological dysfunction is defined as exaggerated or inappropriate response of the immune system, which is mostly targeted at innocuous antigens with consequent tissue damage."  Hypersensitivity reactions are grouped into 4 categories or types; "type I (Immediate), type II (antibody-mediated), type III (immune complex-mediated), and type IV (cell-mediated or delayed-type) hypersensitivity."  

"Type I hypersensitivity or allergy, the most common immune disorder, is mainly mediated by immunoglobulin (Ig)E and mast cells. It can cause anaphylaxis, food allergy, and asthma. Type II hypersensitivity can lead to tissue damage by three main mechanisms: (1) direct cellular destruction (e.g., autoimmune hemolytic anemia and immune thrombocytopenia), (2) inflammation (e.g., Goodpasture's syndrome and acute rheumatic fever), and (3) disrupting cellular function (e.g., myasthenia gravis and Graves’ disease). Type III hypersensitivity is caused by excess production of immune complexes or impaired clearance of them and includes serum sickness, systemic lupus erythematosus, and post-streptococcal glomerulonephritis. Type IV hypersensitivity is mediated by T cells and macrophages, causing diseases like multiple sclerosis and rheumatoid arthritis."

From xPharm: The Comprehensive Pharmacology Reference "Hypersensitivity reactions can involve immunological or non-immunological mechanisms, with the latter also being known as idiosyncratic reactions or pseudo-allergy. Johansson and colleagues Johansson et al (2001) states that “Hypersensitivity causes objectively reproducible symptoms or signs, initiated by exposure to a defined stimulus at a dose tolerated by normal subjects.” The stimulus could include both exogenous and endogenous antigens and haptens. A broader definition of allergy that includes all immunologically-mediated hypersensitivity reactions is now more widely accepted. Allergy is still commonly used to refer to IgE-mediated hypersensitivity."

Specific Symptoms, Conditions, and Diseases:
Allergic bronchopulmonary aspergillosis (ABPA) "is a common fungal infection in uncontrolled asthmatics, cystic fibrosis patients, and immunocompromised patients."

Anaphylaxis -see this post

Anaphylactoid Reaction - Anaphylactoid reactions are defined as those reactions that produce the same clinical picture as anaphylaxis but are not IgE mediated, occur through a direct non-immune-mediated release of mediators from mast cells and/or basophils or result from direct complement activation.
Surviving Anaphylactoid Reactions: Critical Steps You Must Know 

Anaphylactoid Syndrome of Pregnancy -

Angioedema is the swelling of the deeper layers of the skin, caused by a build-up of fluid. 

Asthma

Burning Mouth Syndrome

DRESS (aka DIHS "Drug Induced Hypersensitivity Syndrome") "is a delayed, life-threatening hypersensitivity reaction that can cause severe organ dysfunction, may involve viral reactivation and result in long-term complications. It occurs from taking one of over 50 medications — anticonvulsants, antibiotics, and Allopurinol being the top offenders.

It can affect anyone who takes or is administered medication and can be difficult to predict. However, we are discovering, more and more, that there is a genetic predisposition to DRESS where certain drugs are concerned. This predisposition can vary depending on the drug and the population. For instance, some Han Chinese carry a genetic risk (HLA-B*5801) for DRESS to the gout drug, allopurinol, and some populations of European ancestry carry a high risk (HLA-A*32:01) for a reaction to the antibiotic, Vancomycin." 

Eczema  

Erythropoietic Protoporphyria (EPP) and X-Linked Protoporphyria (XLP) - certain kinds of light cause a reaction in red blood cells, causing them to release chemicals that build up in the liver and damage it.

Eosinophilic Esophagitis

Familial Tryptesemia

Gastroparesis (from Strong Medicine channel)

HaT (Hereditary alpha-tryptasemia) is a relatively common condition, occurring in around 5% of the population (in America and Western Europe)..  It is caused by the presence of extra copies of the gene TPSAB1 (which encodes the protein α-tryptase) and is the most common cause by far of an elevated serum tryptase level.  HaT can cause a person to have heightened anaphylactic reactions to triggers such as insect stings.  It is generally treated the same as MCAS.

Hereditary angioedema  
Management of Children With Hereditary Angioedema Due to C1 Inhibitor Deficiency

Hypocomplementemic urticarial vasculitis syndrome (HUVS)

Hypocomplementemic Urticarial Vasculitis Syndrome or Systemic Lupus Erythematosus in Evolution?
"Hypocomplementemia urticarial vasculitis syndrome (HUVS) is a rare form of systemic vasculitis which is characterized by the presence of urticaria and hypocomplementemia. The presence of recurrent and chronic urticarial rash is the dominant clinical finding in HUVS. Other manifestations including angioedema, arthritis, gastrointestinal symptoms, ocular inflammation, pulmonary involvement, renal involvement, and central nervous system involvement are also seen. Although the pathophysiology of HUVS is yet to be fully understood, it has been demonstrated that immune complex-mediated injury is the predominant mechanism responsible for severe systemic manifestations; a mechanism of injury similar to systemic lupus erythematosus (SLE)."

Hypersensitivity Pneumonitis (Extrinsic Allergic Alveolitis)
"The term hypersensitivity pneumonitis (also known as extrinsic allergic alveolitis) refers to a group of lung diseases in which your lungs become inflamed as an allergic reaction resulting from exposure to dusts of animal and vegetable origin.  Intense or prolonged exposure to animal or vegetable dusts can result in hypersensitivity pneumonitis. The dust particles must be 5 microns or smaller to get into the alveoli. Animal and vegetable dusts are complex mixtures originating from many different sources such as husks, bark, wood, animal dander, and microorganisms including bacteria and fungi. The microorganisms produce toxic chemicals that form part of the mixture. Insects and insect fragments, bird droppings and dried urine of rats may also be found in the dusts. Moldy hay, straw, grain, and feathers are other sources of dust."

Idiopathic Anaphylaxis

Interstitial cystitis

Kounis Syndrome

Mastocytic Enterocolitis
"As mast cells have been highlighted in the pathogenesis of diarrhea-predominant irritable bowel syndrome, a new term "mastocytic enterocolitis" was suggested by Jakate and colleagues to describe an increase in mucosal mast cells in patients with chronic intractable diarrhea and favorable response to treatment with antihistamines."

Oral Allergy Syndrome (OAS, aka "pollen-food allergy syndrome")
This is a cross-reaction between certain pollen and categories of foods that contain proteins that are similar to those pollens, usually when eaten raw because heat destroys the proteins in question (peeling may also help, also eating canned versions of the food).  "OAS is a form of a contact allergic reaction that occurs upon contact of the mouth and throat with raw fruits or vegetables. The most frequent symptoms of OAS include itchiness or swelling of the mouth, face, lip, tongue and throat. Symptoms usually appear immediately after eating raw fruits or vegetables, although in rare cases, the reaction can occur more than an hour later. OAS is generally considered to be a mild form of food allergy. Rarely, OAS can cause severe throat swelling leading to difficulty swallowing or breathing. In a person who is highly allergic, a systemic reaction, called anaphylaxis"

"In the case of OAS, individuals react to different foods based on what type of seasonal allergies they are affected by. For instance, if you are allergic to birch tree pollen, a primary airborne allergen responsible for symptoms in the springtime, you may have reactions triggered by pitted fruit or carrot. Even peanuts, almond, and hazelnut may cause mouth itching in those with birch pollen allergy. People with allergies to grasses may have a reaction to peaches, celery, tomatoes, melons (cantaloupe, watermelon and honeydew) and oranges. Those with reactions to ragweed might have symptoms when eating foods such as banana, cucumber, melon, and zucchini." 

Scombroid Syndrome or histamine fish poisoning is a histamine toxicity condition resulting from the consumption of spoiled fish [12]. Fish flesh contains the amino acid histidine. When fish is infected by gram-negative bacteria that contain the enzyme histidine decarboxylase, this enzyme converts histidine to histamine, which induces Kounis syndrome.

Anisakiasis is another condition associated with ingesting raw or undercooked fish or seafood. It occurs when seafood is infested with anisakis simplex, a common nematode parasitizing fish, which secretes allergenic substances. Therefore, unlike scrombroid syndrome, anisakiasis is an IgE-mediated food allergy and future abstention from eating raw or undercooked fish or seafood is always required.

Yao Syndrome (formerly called NOD2-associated autoinflammatory disease) "is a disorder involving episodes of fever and abnormal inflammation affecting many parts of the body, particularly the skin, joints, and gastrointestinal system."

Immunological Conditions
CVID (Common Variable Immune Deficiency)

Erythema multiforme is an immune-mediated skin rash that be recurring and be confused with allergic skin conditions such as atypical urticaria and atopic dermatitis.  It is usually caused by a reaction to a medication or by the Herpes Simplex Virus.  Because the rash has a target-like appearance it can be confused with Lyme Disease as well.  

WHIM Syndrome (Warts, Hypogammaglobulinemia, Immunodeficiency, Myelokathexis)