Monday, February 26, 2007

Intestinal Epithelial Cells Defend Against Invaders

"How the immune system is switched on and off, or how it detects friend or foe, has baffled scientists for years. New research from the University of Pennsylvania School of Veterinary Medicine shows that tiny cells called intestinal epithelial cells play a central role in both turning on anti-microbial immune responses and turning off harmful responses that can cause chronic inflammation in the intestine.

The researchers report their findings in Nature. ..."

[Click the title to read the full article]

Friday, February 23, 2007

Are Modern Foods the Main Underlying Factor In the Molecular Mimicry Of Autoimmune Diseases?

Molecular mimicry caused by similarities between cells in modern foods, infectious agents and human self tissues has been identified as a mechanism for the development of autoimmune disease in the case of celiac disease and is likely involved in other autoimmune diseases. This may be the most crucial aspect of evolutionary nutrition, and the most important area of research in evolutionary medicine.

SUMMARY:
> some modern, agricultural foods (grains, dairy and legumes) contain high concentrations of proteins that are structurally similar (homologous) to proteins in humans, bacteria and certain viruses; these homologous proteins have similar cell structures due to their similar peptide sequences (a.k.a. amino acid sequences)
> bacteria and certain viruses have these homologous protein cells on their surfaces, and they use them for attachment, locomotion and transmission
> the human body has its homologous protein cells on the surfaces of many of its internal and external tissues; they often even look similar to their bacterial and viral counterparts, frequently having a hair-like, bristle-like, filamentous, or whip-like appearance (which is characteristic of many fibrous proteins and filamentous globular protein chains); these homologous protein cells are often the targets of a misdirected immune system in autoimmune illness

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HISTORY

A possible connection between food and autoimmune disease was suggested as early as 1981 (Ronald Williams, MD, "Rheumatoid arthritis and food: a case study." British Medical Journal, 1981; 283:563). In 1996, Dr. Kalle Reichelt proposed that dietary proteins "may be responsible for many autoimmune diseases" through molecular mimicry (Kalle Reichelt, M.D., Food and mental problems, 26 Feb 1996, http://gluten-free.org/reichelt.html). Margo C. Honeyman et al suggested a three-way molecular mimicry link between dietary proteins (in milk, wheat and beans), viruses and human cells (Margo C. Honeyman, Stone NL, Harrison LC, "T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents," Molecular Medicine, 1998 Apr;4(4):231-9:). This three-way link is the current form of the dietary molecular mimicry hypothesis.

Loren Cordain, Ph.D. explained why and how modern food proteins trigger molecular mimicry by using Dr. S. Boyd Eaton's theory of evolutionary dietary discordance* ("The Late Role of Grains and Legumes in the Human Diet, and Biochemical Evidence of their Evolutionary Discordance," by Loren Cordain, Ph.D., copyright 1999, http://www.beyondveg.com/cordain-l/grains-leg/grains-legumes-1b.shtml). Cordain focused on the best understood case of food proteins triggering autoimmune disease--wheat gluten's triggering of celiac disease. He pointed out that "wheat contains peptide sequences which remain undigested and which can enter into systemic circulation" and that "These peptide sequences are homologous to a wide variety of the body's tissue peptide sequences and hence induce autoimmune disease via the process of molecular mimicry." Cordain posited that "All autoimmune diseases develop because of interactions between the genes and one or more environmental factors, such as a viral or bacterial infection or exposure to a certain food." Cordain cited rheumatoid arthritis, multiple sclerosis, and type 1 (juvenile) diabetes as examples of autoimmune diseases. Ray Audette, author of NeanderThin, expanded on the list by mentioning "arthritis, diabetes, allergies, colitis, Crohn's disease, multiple sclerosis, Alzheimer's, endometriosis, many forms of cancer, lupus, and most arterial diseases (heart attacks and strokes)" (Ray Audette, NeanderThin, 1999, p. 17).

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The full story involves more than just gluten and celiac disease. There appears to be a general mimicry link between modern food proteins and surface proteins in the cells of human tissues and infectious agents (bacteria and certain viruses). The surface proteins of mitochondria in humans may also be involved. The common factor shared by these food and human cell proteins is that they are similar to the surface proteins of bacteria and viruses that the human immune system has evolved defenses against. Interestingly, many of these surface proteins appear to share a hair-like (filamentous or bristly) structure in these three sources (modern foods, human tissues, and infectious agents). If these proteins are investigated, further amino acid sequence similarities may be found beyond those which have been identified.

Types of bacteria surface proteins and the structure(s) they are found in:
> hair-like fibrous glycoproteins - fimbriae (pili), and possibly the fibrous sheath of the flagellum
> filamentous globular proteins (tubulins) - core of the flagellum (surrounded by a fibrous sheath)
> transmembrane proteins (composed of beta strands connected into sheets) - porins

Types of virus surface proteins and the structure(s) they are found in:
> hair-like fibrous (external transmembrane) glycoproteins - peplomers (spikes)
> other transmembrane glycoproteins such as hemagglutinin (HA), the fusion protein of influenza viruses

Homologous human proteins and the structure(s) they are found in:
> hair-like fibrous proteins - epithelial cell proteins such as collagens, keratins (found in such human structures as skin, hair, nails, tooth enamel, liver bile ducts, the salivary gland, the bladder, ureters, eyelashes, nose hairs, and external ear hairs), elastins, f-actin, and myosin
> globular proteins - albumins, globulins, histones, protamines, microtuble associated proteins (composed of tau proteins) and tubulins (found in such human structures as axons and dendrites, cilia of the kidney nephrons, oviducts, the uterus, the upper two thirds of the cervix, sinus cavity and mucus membranes, and nose cilia), kinase proteins (enzyme proteins found in such human structures as villi and microvilli of the small intestine, tongue villi, axons and dendrites, breast ducts and mammary gland, salivary gland, bladder, ureters, bronchial tubes of the lungs, certain pancreatic cells, gingival tissues, and skin)
> both fibrous and globular proteins like actin (which has both globular and fibrous forms), myosin (fibrous) and calreticulin (globular) can be found in smooth muscle cells
> transmembrane proteins (composed of beta strands connected into sheets) - porins in mitochondria (mitochondria are descendants of ancient bacteria)

Homologous modern food proteins and the food(s) they are found in:
> hair-like fibrous proteins - glycine-rich cell wall protein (GRP) [though a Wikipedia article claims that "Fibrous proteins are only found in animals"], which is in the cell walls of cereal grains and legumes, shares significant amino acid homology with human keratins, fibrillar collagen and procollagen, and with the Epstein-Barr virus nuclear (EBV) antigen-I (EBNA-I) [source: Claudio Lunardi et al, "Glycine-rich cell wall proteins act as specific antigen targets in autoimmune and food allergic disorders," International Immunology, Vol. 12, No. 5, 647-657, May 2000, http://intimm.oxfordjournals.org/cgi/content/full/12/5/647]
> globular proteins - gliadin, a lectin glycoprotein found in various forms in wheat, rye, barley, and other grains that shares homologous peptide sequences with human calreticulin; gliadin and other cereal grain prolamines (proteins with a high proline content) are homologous to Adenovirus 12E1b; high-molecular weight glutenin, a protein found in wheat, rye, barley and other grains that is homologous to human elastin; hemagglutinin, a lectin found in soy and potato that is homologous to influenza virus proteins hemagglutinin HA1 and HA2

The human immune system is rough, rather than precise, which gives it the ability to develop defenses against ever-changing infectious agents. This unfortunately also makes it more susceptible to mis-identifying food proteins and proteins in the surfaces of self tissues as infectious agents.

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* Dr. Cordain credited Dr. Eaton thusly: "Although a few physicians, scientists, and anthropologists had been aware of this concept, it was Dr. Eaton's writings that brought this idea to center stage" (Loren Cordain, Ph.D., The Paleo Diet, Hoboken, NJ: John Wiley & Sons, 2001, p. 4).

SUGGESTED READING:

"The Late Role of Grains and Legumes in the Human Diet, and Biochemical Evidence of their Evolutionary Discordance," by Loren Cordain, Ph.D., copyright 1999, http://www.beyondveg.com/cordain-l/grains-leg/grains-legumes-1b.shtml

Claudio Lunardi et al, "Glycine-Rich Cell Wall Proteins Act as Specific Antigen Targets in Autoimmune and Food Allergic Disorders,"
International Immunology, Vol. 12, No. 5, 647-657, May 2000, http://intimm.oxfordjournals.org/cgi/content/full/12/5/647