IgE and Allergy
IgE is according to Wikipedia:
It’s Role in Disease:
Atopic individuals can have up to 10 times the normal level of IgE in their blood (as do sufferers of hyper-IgE syndrome). However, this may not be a requirement for symptoms to occur as has been seen in asthmatics with normal IgE levels in their blood – recent research has shown that IgE production can occur locally in the nasal mucosa, without the involvement of lymphoid tissue.
IgE that can specifically recognise an “allergen” (typically this is a protein, such as dust mite DerP1, cat FelD1, grass or ragweed pollen, etc.) has a unique long-lived interaction with its high affinity receptor, FcεRI, so that basophils and mast cells, capable of mediating inflammatory reactions, become “primed”, ready to release chemicals like histamine, leukotrienes and certain interleukins, which cause many of the symptoms we associate with allergy, such as airway constriction in asthma, local inflammation in eczema, increased mucus secretion in allergic rhinitis and increased vascular permeability, ostensibly to allow other immune cells to gain access to tissues, but which can lead to a potentially fatal drop in blood pressure as in anaphylaxis. Although the mechanisms of each response are fairly well understood, why some allergics develop such drastic sensitivities when others merely get a runny nose is still one of science’s hot topics. Regulation of IgE levels through control of B cell differentiation to antibody-secreting plasma cells is thought to involve the “low affinity” receptor, FcεRII or CD23. CD23 may also allow facilitated antigen presentation, an IgE-dependent mechanism whereby B cells expressing CD23 are able to present allergen to (and stimulate) specific T helper cells, causing the perpetuation of a Th2 response, one of the hallmarks of which is the production of more antibodies.
“A major unsolved challenge in adjuvant development is how to achieve a potent adjuvant effect while avoiding reactogenicity or toxicity.3 Most newer human adjuvants including MF59,4 ISCOMS,5 QS21,6 AS02,7 and AS048 have substantially higher local reactogenicity and systemic toxicity than alum. Even alum, despite being FDA-approved, has significant adverse effects including injection site pain, inflammation, and lymphadenopathy, and less commonly injection-site necrosis, granulomas, or sterile abscess.9 Although many adjuvant-caused vaccine reactions are not life-threatening and do resolve over time, they remain one of the most important barriers to better community acceptance of routine prophylactic vaccination. This particularly applies to pediatric vaccination where prolonged distress in the child due to increased reactogenicity may lead directly to parental and community resistance to vaccination.10 Hence, particularly in the context of childhood prophylactic vaccines, it is critical that suitable adjuvants be developed with lower reactogenicity and greater safety. Ideally, in addition to being safe and well tolerated, adjuvants should promote an appropriate (humoral and/or cellular) immune response, have a long shelf-life, and should be stable, biodegradable, cheap to produce, and not induce immune responses against themselves…”
Aluminum Salts (Alum) Aluminum, once ingested, is toxic to cells13 and by the time they reach the draining lymph node most of the macrophages that have ingested aluminum particles will be dead or dying. Once necrotic, the macrophages release their cytoplasmic contents, including alum-absorbed antigen and inflammatory mediators such as IL-1 and TNF, into the lymph. This provides a source of macrophage cell debris, antigen, and co-stimulatory cytokines flowing into the draining lymph node, a potent mix to stimulate antigen-specific plasma cells and antibody production. Interestingly, a similar mechanism was proposed many years ago to explain the adjuvant action of beryllium, a compound which is even more toxic to macrophages than aluminum, and has potent adjuvant activity.
Limitations of alum. Although aluminum salts remain the most commonly used adjuvants and the only ones currently approved for use in humans by the FDA, they suffer from a number of downsides, including inability to induce cytotoxic T-lymphocyte (CTL) responses critical in many cases for viral protection and clearance.15 Well-recognized problems of aluminum adjuvants include local injection site reactions, stimulation of eosinophilia, augmentation of IgE antibody responses, ineffectiveness for some antigens, and failure to enhance CTL responses. Alum is reasonably well tolerated when injected intramuscularly, with only mild to moderate injection pain and occasional granulomas. Risk of granulomas becomes particularly high when alum-based vaccines are injected subcutaneously or intradermally. Consequently, alum-containing vaccines are generally given by intramuscular injection.
The mechanism for alum’s tendency to stimulate eosinophilia and enhance IgE production is unknown, but its consequence is an increased risk of vaccine allergy and anaphylaxis.9,16,18,19 This potential has been demonstrated in animal models of ovalbumin-induced asthma or anaphlylaxis, which are dependent on alum in the initial priming. In humans, there have been reports of a chronic inflammation syndrome called macrophagic myofascitis (MMF) being induced by alum-based vaccines.
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In an online paper in the journal Nature, Yale University researchers funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, explain how a common ingredient in many vaccines stimulates and interacts with the immune system to help provide protection against infectious diseases.
Vaccines must possess not only the bacterial or viral components that serve as targets of protective immune responses, but also ingredients to kick start those immune responses. In many vaccines, the bacterial or viral components themselves have this capability. For other vaccines, the immune system requires an added boost. Adjuvants are those substances added to a vaccine to help stimulate the immune system and make the vaccine more effective.
Currently the only vaccine adjuvants licensed for general use in the United States are aluminum hydroxide/phosphate formulations, known as alum. Although alum has been used to boost the immune responses to vaccines for decades, no one has known how it worked.
In this paper, the Yale team, led by Richard Flavell, M.D., Ph.D., and Stephanie Eisenbarth, M.D., Ph.D., examined the immune system pathway and cell receptors used by alum. Many microbial compounds function as adjuvants by stimulating Toll-like receptors. These receptors identify microbial invaders and alert the body to the presence of a disease-causing agent, or pathogen. Alum, however, does not stimulate Toll-like receptors. The Yale team found that alum stimulates clusters of proteins called inflammasomes, found inside certain cells. Inflammasomes respond to stresses such as infection or injury by releasing immune cell signaling proteins called cytokines. Inflammasomes are a component of the innate immune system that operates in parallel with, but separate from, Toll-like receptors, also part of the innate immune system.
To make this determination, Dr. Eisenbarth and her coworkers used mice that had been genetically engineered to be deficient in various components of a specific type of inflammasome, characterized by the presence of the protein termed Nalp3. The team demonstrated that an immune response did not occur in those animals with the deficient Nalp3 inflammasomes, despite the inclusion of alum, while it did occur in normal mice. The team’s findings provide the first convincing evidence that the Nalp3 inflammasome forms the basis for alum’s adjuvant action.
According to the study authors, several unanswered questions remain regarding how activation of this pathway controls a highly specific and long-lasting immune response generated by a vaccine. But this new information on the molecules that alum uses to activate the innate immune system should provide the keys to better understanding adjuvant function and should facilitate the design of new vaccine adjuvants.
…In 1996, the American Academy of Pediatrics issued a position paper on Aluminum Toxicity in Infants and Children which stated in the first paragraph, “Aluminum is now being implicated as interfering with a variety of cellular and metabolic processes in the nervous system and in other tissues.
A review of the medical literature on aluminum reveals a surprising lack of scientific evidence that injected aluminum is safe. There is limited understanding of what happens to children when aluminum is injected into their bodies, including whether or not it accumulates in tissues and organs or is properly eliminated from the body. It is also unknown if genetic factors affect long term adverse health outcomes for those injected with aluminum containing vaccines.
…Ten percent of all children have asthma. Growing numbers of children are living with different types of allergies. That means they have impairment, or even irreversible damage to their nervous and immune systems. Isn’t it possible that injected aluminum plays a role in affecting the health of our children’s nervous and immune systems, as the science we do have seems to suggest?
What is even more concerning is the lack of accepted scientific data explaining whether injected aluminum interacts with other vaccine ingredients to cause harm to our children. Boyd Haley, PhD, Professor Emeritus of Chemistry at the University of Kentucky completed lab experiments showing the damaging effects on nerve cells when he exposed them to aluminum, especially in the presence of other vaccine ingredients like mercury, formaldehyde, and the antibiotic neomycin.  His data, however, have been ignored by the scientific, medical and governmental institutions making vaccine policies. The scientific community needs to be doing these experiments in the lab before shooting kids with these ingredients and declaring unequivocal vaccine safety for all children.
…Aluminum is placed in the vaccines to selectively target the up-regulation of the humoral arm (TH2 cells) of children’s immune systems, to drive the production of antibodies. The medical community leads us to believe that this production of antibodies is what imparts for children a protective nature against vaccine-preventable illnesses. Yet, this outcome may come at a cost.
There are multiple articles in the medical literature demonstrating how chronic illnesses like allergies,  asthma,    eczema, lupus,  inflammatory bowel disease,  ADD/ADHD and autism all exhibit a skewed production and over-activity of the TH2 arm of the immune system.
Similarly, chronic illnesses like juvenile diabetes mellitus  and rheumatoid arthritis, multiple sclerosis, uveits, inflammatory bowel disease, and autism  all exhibit skewed production and over-activity of the TH1 arm of the immune system.
…What is clear is aluminum pushes the TH2 immune system to over perform, and multiple chronic illnesses in children show immune systems where the TH2 immune response over performs, while TH1 and TH3 responses are also impaired. Is there a connection? By having this type of effect on the TH2 system, is aluminum in any way contributing to the development of these chronic illnesses in children; especially in those children from families with a genetic history of the above mentioned chronic illnesses?
…Under these circumstances, the activity of aluminum appears to play a vital role in disrupting the maturation of the immune system in infants and children through its effects on TH2 and therefore, on TH1 and TH3.
…We have no scientific studies in infants, children or adults to help us understand the nature of the progression of TH1, TH2 and TH3 immune responses to any of the injected materials in vaccines.
After about 70 years two new adjuvants have been approved for human vaccines. The first is MF59 developed by the ex-Chiron now Novartis Vaccines and it consists in an oil-in-water emulsion, comprising a low content of biodegradable squalene oil (4.3%) as the dispersed phase, which is stabilized by two non-ionic surfactants (Tween 80 and Span 85), and a low ionic strength citrate buffer as the continuous phase. The second one, defined as AS04, has been developed by GSK Biologics and consists in 3-0-desacyl- 4′-monophosphoryl lipid A (MPL) that comes from the cell wall LPS of Gram-negative Salmonella minnesota R595 and is detoxified by mild hydrolytic treatment and purification. It is absorbed on aluminum hydroxide or aluminum phosphate. Thus, new molecules are available to improve the immune response to vaccines also in humans: this is the beginning of a new era in vaccinology.
MRL means “minimum risk level”. At that point you might start seeing toxic effects such as psychosis. At the two, four, and 6 month shots, it’s clearly exceeded. Only the aluminum amounts from DTaP and HepB were used. However, babies often get in addition to that, HIB and Prevnar.
Workshop on Aluminum in Vaccines, San Juan , Puerto Rico. May 11, 2000. Pg. 170+
Edited to add:
A team of scientists have investigated a case of vaccine-associated chronic fatigue syndrome (CFS) and macrophagic myofasciitis in an individual demonstrating aluminium overload.
This is the first report linking aluminium overload with either of the two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in a patient.
The team, led by Dr Chris Exley, of the Birchall Centre at Keele University in Staffordshire, UK, has found a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events that are associated with autoimmune conditions, including chronic fatigue syndrome and macrophagic myofasciitis.
The CFS in a 43-year-old man, with no history of previous illness, followed a course of five vaccinations, each of which included an aluminium-based adjuvant. The latter are extremely effective immunogens in their own right and so improve the immune response to whichever antigen is administered in their presence. While the course of vaccinations was cited by an industrial injuries tribunal as the cause of the CFS in the individual, it was not likely to be a cause of the elevated body burden of aluminium. The latter was probably ongoing at the time when the vaccinations were administered and it is proposed that the cause of the CFS in this individual was a heightened immune response, initially to the aluminium in each of the adjuvants and thereafter spreading to other significant body stores of aluminium.
The result was a severe and ongoing immune response to elevated body stores of aluminium, which was initiated by a course of five aluminium adjuvant-based vaccinations within a short period of time. There are strong precedents for delayed hypersensitivity to aluminium in children receiving vaccinations which include aluminium-based adjuvants, with as many as 1% of recipients showing such a response.
While the use of aluminium-based adjuvants may be safe, it is also possible that for a significant number of individuals they may represent a significant health risk, such as was found in this case. With this in mind the ongoing programme of mass vaccination of young women in the UK against the human papilloma virus (HPV) with a vaccine which uses an aluminium based adjuvant may not be without similar risks.
Recent press coverage of myalgic encephalomyelitis (ME) or chronic fatigue syndrome has highlighted the potentially debilitating nature of this disease and related conditions. The cause of CFS is unknown.