Science behind immunopathology

Immunopathology is an increase in one's present symptoms of Th1 inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue., or a return of previous Th1 inflammatory symptoms, that is caused largely by cytokinesAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. generated by the immune response and endotoxins released from dying bacteria. Occasionally, immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed. will consist of a new symptom or abnormal lab value (e.g., elevated creatinine, elevated liver enzymes, low white blood count, etc.) due to the occurrence of subclinical bacterial inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. that has been revealed by the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis.. Immunopathology is a necessary part of recovery. The amount of immunopathology a patient experiences on the Marshall Protocol (MP) is correlated with disease severity and bacterial load. Patients who are less sick will have comparatively less strong immunopathology.

Immunopathology is sometimes used synonymously with the “Jarisch-Herxheimer reaction” or “herx.”

That many MP patients who have experienced prolonged periods of immunopathology have reached stages of significant improvement or remission helps validate the conclusion that the reaction is a result of chronic bacterial death. The MP is not unique in this regard. A number of other diseases and/or therapies generate immunopathological or immunopathological-like reactions.^{1) 2) 3)}

Lab work and patient reports can be used to track clinical signs of immunopathology.

In patients sick with any of the Th1 diseases, pulsed low-dose antibiotics and frequent administration of olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. kill intraphagocytic and other pathogenic forms of bacteria. When bacteria die, endotoxins and inflammatory cytokines (signaling molecules) are released at the site of infection.

Example of immunopathology – Members of the observational cohort tend to experience temporary increase in several antibody titers, and a decline in latter stages of treatment.⁴⁾

During immunopathology, cytokines, are elevated. Although cytokines are usually associated with an inflammatory process, it has been demonstrated in two studies that tumour-necrosis factor (TNF), interleukin-6 (IL-6) and IL-8 are involved with the Herxheimer reaction, each peaking at different times throughout the reaction; TNF elevates first, shortly after antibiotic administration, followed by IL-6 at the onset of symptoms and finally IL-8.⁵⁾⁶⁾

The release of cytokines appears to be essential for recovery after an infection. One study found that the cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. TNF-alpha was essential for the proper expression of acquired specific resistance following infection with Mycobacterium tuberculosis.^{7) 8) 9)} For this reason among others, TNF-alpha inhibitors, drugs which suppress the cytokine, are contraindicated for MP patients.

Endotoxins are proteins associated with the outer membranes of bacteria, especially gram-negative bacteria. When these bacteria are destroyed as will happen during the MP, endotoxins are released causing a spike in symptoms known as the immunopathological reactionA temporary increase in disease symptoms experiences by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed..

There is clear experimental evidence that antibiotics [can] increase the bioavailability of endotoxin from Gram-negative bacteria.

J. C. Hurley¹⁰⁾

The presence of endotoxins is a commonly used indication for the presence of gram-negative bacteria. For example, studies examining the quality of ultrapure dialysis water use endotoxin levels – in one case, >5 IU/ml¹¹⁾ – as an indication that the water has been infected by bacteria.

Symptom levels on the MP wax and wane over time due to immunopathology. In practice, the variation in symptoms tends to be more random than this illustration suggests, but there is a distinct downward trend.

The increase in endotoxin and cytokines causes a corresponding increase in symptoms. Sometimes the symptoms are generalized and may include pain and fatigue. Other times symptoms occur at the site of infection. Patients with the lung disease sarcoidosis may notice that their coughing spells get worse. Those with psoriasis may notice a flare in their skin symptoms.

Cardiac, neurological, and respiratory immunopathology should be of particular concern to healthcare providers as they can be life-threatening.

Occasionally, patients may notice new symptoms occurring in organs not known to be infected. The MP does not and cannot create new inflammation.

The strength of an immunopathological or herx reaction is associated with the severity of disease.¹²⁾¹³⁾

The Jarisch-Herxheimer reaction, which is similar if not identical to immunopathology, is accepted as an indication of progress and, according to the literature, has been observed in at least ten different diseases and conditions:

• syphillis including neurosyphillis¹⁴⁾ and syphillitic alopecia¹⁵⁾
• Lyme disease¹⁶⁾
• Borrelia infection¹⁷⁾
• multiple sclerosis^{18) 19)}
• tuberculosis²⁰⁾
• leptospirosis²¹⁾
• Whipple disease²²⁾
• sarcoidosis²³⁾
• relapsing fever²⁴⁾

Recovery from other infections and diseases also entails an immunopathological-like response.

Fever, a natural increase in one's body temperature, has been conserved during evolution through millennia, because of its advantage for host defense.²⁵⁾ Important immunological reactions are sped up by temperature, and some pathogens with strict temperature preferences are hindered.²⁶⁾

Immune reconstitution inflammatory syndrome or IRIS is a condition seen in some cases of AIDS often following the use of antiretroviral drugs, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.²⁷⁾

Another example of immunopathology can be observed in the body's response to the rhinovirus. The symptoms of the common cold, which is caused by the rhinovirus, are an indication that the human host is in the midst of an activated immune response. Researchers have shown that during the common cold, the expression of many genes associated with the immune response, including chemokines and antivirals, are altered.²⁸⁾ It's important to note that the rhinovirus doesn't exactly cause the immune response so much as trigger it.

Similarly, olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. and MP antibiotics do not cause the immunopathological reaction so much as trigger it.

Given its pervasiveness across diseases, immunopathology belies the common assumption that feeling well is the same as being healthy.

In observing a set of worsening symptoms, patients and clinicians may be tempted to assume that the disease itself is worsening. Even a small number of researchers are mistakenly convinced that antibiotics cause or exacerbate chronic disease. The best example of this may be so-called “minocyclineBacteriostatic antibiotic used by Marshall Protocol patients.-induced lupus.”²⁹⁾ In fact, there is no reasonable mechanism, proven or theoretical, which explains how minocycline, the primary action of which is to block the 30s ribosome of bacteria, can cause lupus – or any other disease.³⁰⁾

Edward L. Krawitt, M.D. has it right when he suggests the possibility that minocycline, an MP antibiotic, “unmasks” autoimmuneA condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body hepatitis.³¹⁾

In the same vein, a so-called “allergic” reaction to minocycline or any of the other MP antibiotics is invariably due to the immunopathological response generated by taking olmesartan (Benicar) and antibiotics.

Two German papers have noted that the Jarisch-Herxheimer reaction can be suppressed with the administration of different kinds of prednisolone, a powerful corticosteroidA first-line treatment for a number of diseases. Corticosteroids work by slowing the innate immune response. This provides some patients with temporary symptom palliation but exacerbates the disease over the long-term by allowing chronic pathogens to proliferate..³²⁾³³⁾

One of the factors in the incidence and prevalence of chronic disease is that the immunopathological reaction is being systematically inhibited on a population-wide basis. There are a broad range of substances including prescription drugs, supplements, and foods that inactivate the innate immune responseThe body's first line of defense against intracellular and other pathogens. According to the Marshall Pathogenesis the innate immune system becomes disabled as patients develop chronic disease.. These include, among many others:

• corticosteroids
• vitamin D
• soy
• TNF-alpha inhibitors