From the Archives
Added online October 2016
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Case 5: Dr. Wright made a night call to a household with diphtheria. Arriving home, he stabled his horse and, to prevent contagion, changed his clothes in the barn. Before going to bed, he paused to look through the doorway at his only son, baby George. The baby sickened and died of diphtheria the following week.
Tetanus and diphtheria were dreaded killers in preantibiotic times. By the 1890s, physicians had learned how to protect people after they'd been exposed – by giving passive immunity, the kind that a baby gets from its mother. Horses were injected with the deadly toxins and those that survived became immune – with lots of protective immune globulins circulating in their blood. This immune horse serum was injected and it protected the recipient.41,42 A century later, we have better methods, but we must honor the innovative scientists of the Gaslight Era!43
They also knew that injections should not be contaminated with bacteria. To prove the horse serum sterile, they injected rabbits with some of each batch – and watched to see if an abscess would develop. These frugal scientists found they couldn't use the same rabbits repeatedly: Previously injected rabbits often died immediately after the shot.44 Nicolas Arthus noted that the surviving rabbits developed slow-healing lumps or nasty ulcers at the test site over a few days.45 Humans had similar problems after repeated injections of horse serum – not with the first but on repeated injections.46
The fledgling science of immunology couldn't explain all this, but it tried. In 1921, Otto Prausnitz and Heinz Küstner demonstrated quite clearly that the immediate hypersensitivity of severe food allergy – and of hay-fever and fatal horse serum injections – is caused by a reactive substance in the serum.47 They called it reagin, but we now know it as immunoglobulin E (IgE).48,49 The allergists of the world reportedly took heart at the demonstration of reagin in the "P-K reaction": Now their skin tests and allergy shots had a solid experimental basis, affording their treatments greater validity, if not gravitas.
What of the rabbits' ulcers, the astute critic might ask? Because they weren't fatal, they were largely ignored. Scientists later showed that these lesions were caused by rabbit immunoglobulin binding to horse proteins, causing inflammation of blood vessels – "vasculitis."50
Immunology Becomes Politicized
Following Prausnitz and Küstner's epochal report, leading immunologists – first in Europe and then in the US – agreed from thence forward that they would define allergy solely in conformity with the P-K reaction. Arthur Coca, who coined the term atopy and developed the solution still used to make allergy extracts, protested this decision.51,52 He stated that many types of food reactions did not fit the P-K model (being "nonreagenic/nonatopic"), but he and his supporters were voted down.53
The argument was not resolved, though; it got worse. As the world's allergists embraced the creed and catechism of reagin (IgE), groups of members found (as did Coca) that it did not encompass their clinical experience. They left to form their own, less-dogmatic societies. First to go were the ear, nose, and throat specialists in 1941, then general practitioners in 1956, and finally dissenting internists and pediatricians in 1965.54-56
The dispute over defining allergy became so acrimonious that there could be no reconciliation even after 1963, when Gell and Coombs showed that there are at least 4 major types of acquired immune responses.57 Their four "classical" pathways are:
- type 1 reactions, caused by IgE (hay fever); they occur within minutes and give us protection against parasites;
- type 2 reactions, caused when immunoglobulin types G (IgG) or M (IgM) attach themselves to a foreign protein and provoke the complement cascade; these develop over hours to a day and protect against bacteria and viruses;
- type 3 reactions (Arthus reactions), occurring when IgG binds to a dissolved foreign substance and precipitates as an irritating, inflammatory complex; they occur in hours to a day and offer protection against toxins;
- type 4 reactions, caused by sensitized T-cells; these reactions peak at 48–72 hours (e.g., Tb skin-tests) and protect against bacteria.
In the opening paragraph, it was stated: "There is a third way fungi (mold, yeast, etc.) can make us sick. This is generally neglected because of scientific orthodoxy and institutional dogma." The important fact that hay fever allergy, the IgE-mediated, type 1 pathway called "allergy" does not activate the complement cascade.58
Are the majority of allergists correct, those who believe that mold can stimulate the immune system only through type 1, IgE-mediated reactions? If so, Shoemaker's observations that mold activates complement must be explained only as a direct effect of mold toxins, without acquired immunity.59
But antigen-antibody complexes (types 2 and 3 reactions) trigger the complement cascade (and type 4 may also be involved with complement).60 What if the dissenting allergists are right; what if molds do indeed stimulate these late and delayed immune reactions? That would mean that nontoxic molds can trigger complement – and that we are dealing with a broader problem than mold toxins alone. Treatments for these two conditions are very different.
Seeking the Truth
Think for yourself and question authority.
– Timothy Leary, PhD
Allergists in the US agree that type 2–4 immune reactions – call them "late and delayed" reactions (L/D) – can be clinically important, causing asthma and other stubborn problems. However, for most, orthodoxy requires them to believe that type 1 reactions must trigger significant L/D hypersensitivity.
So, when skin tests show no immediate reaction but only later develop large red bumps lasting days to weeks, these lesions are dismissed. An academy expert describes these as "a delayed, IgE dependent reaction, without sufficient IgE to result in an immediate reaction" (does this sound strained?). 61 In a personal communication, a past-president of an allergy academy said his opinion was that such mold test results are "meaningless Arthus reactions" and the patient's symptoms were called "nonallergic."
Delayed type hypersensitivity to fungi was identified and described long ago.62 However, in keeping with the IgE-orthodoxy, delayed type reactions on skin tests were attributed to "pathogenic fungi" and the immediate type (IgE)-sensitivity was associated with non-pathogenic, or allergenic, fungi. In this author's experience of recording late and delayed reactions after intradermal tests, the distinction is questionable.63,64 It is plausible that Arthus reactions are not "meaningless" – and that the type of sensitivity is what renders the fungus pathogenic, rather than the implied converse.
How would allergists learn any differently? Commonly, protocols for provocation challenges require first, determining which allergens should be tested by positive skin tests.65 While sensible and efficient if IgE were indeed required to precede all significant hypersensitivity reactions, this protocol clearly excludes all of what Coca (in 1943) called "nonreagenic" reactions.
Fortunately, some researchers have used a different approach, challenging common allergens regardless of their skin test responses. This is far from inefficient: they've found that a significant number of allergens provoking airway reactions were negative on skin tests – up to 45% (and only 14% IgE-RAST-positive!).66,67 Indeed, antigens can provoke late or delayed reactions with no preceding immediate response – the "isolated late type" in 35% and "isolated delayed type" in 10%.68 This is "key" information: Antigens that do not provoke immediate hypersensitivity ("non-IgE") can cause clinically significant immunological reactions.
Human–Fungus Interfaces and Hypersensitivity
Before science described the fungus kingdom, humanity had given its members common names: mold, mildew, yeast, rusts, smuts, and blights – they are all fungi and are rather similar.69 Fungi are always present in the human environment. They live in our homes and the great outdoors and we breathe them. They populate our food, often intentionally: With fungus, bread is raised and wine fermented.70 Blue cheese is made with Penicillium and soy sauce uses Aspergillus (black mold!).71,72
Fungus also lives on and inside humans: Aspergillus and Candida normally live in the external ear canal.73 Fungus can (and does) live in anyone's gut – the frequency and dominant species are related to diet; knowledge about these populations is advancing with new analytic methods.74 The healthy human has up to 10,000 fungi per gram of stool; Candida species are most common.75,76 Informal polling at medical meetings indicates that Geotrichum (Camembert cheese), Rhodotorula, and other fungi are also seen (less frequently) on stool cultures.77
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