Thymic Protein A
Introduction: Cell-Mediated Basic Immunity
immune system is a complex network of specialized organs, glands and cells
which when working properly protect the body from pathogens such as virus,
bacteria, fungus and foreign tissue such as cancer. This system is composed
of two basic sub-systems, the Humoral and the Cellular or Cell Mediated.
These two sub-systems have different methods of defending the body from
disease. The Humoral side uses chemical warfare, antibodies, to defeat invading
pathogens. Cell Mediated Immunity employs an army of cells to attack and
kill invaders. This is the bodies mechanism for immune response to specific
viruses and cancer.
B-lymphocytes (B-cells) and T-lymphocytes (T-cells) are sub-populations of white blood cells and are the soldiers used by the immune system. B-cells are the antibody producers used in Humoral Immunity; T-cells are the shock troops used in Cell Medicated Immunity. They are all born in the bone marrow, but they mature differently. B-cells mature in the bone marrow, hence the B for bone marrow. T-cells are matured by proteins produced by the thymus gland, hence the T for thymus.
Both sides of the Immune System must function properly in order fro the body to have an optimum Immune Response to invading pathogens. In fact, B-cells will react quicker, proliferate, expand clonally and produce an antibody response more efficiently in the presence of a T-cell response. So it could be said that T-cells drive B-cells to an extent.
Central to beginning the immune response is activation of the T-4 lymphocyte (helper cell). Activation takes place when the T-4 cell recognizes the antigen displayed by an invading pathogen. Once activated the T-4 cell produces Interleukin and Interferon proteins also called lymphokines or cytokines, but more simply defined as immune proteins. These immune proteins in turn activate or program T-8 lymphocytes (killer cells). When the killer cell is programmed, it is programmed to find and kill the specific antigen producing pathogen. Additionally, the activated T-4 cell causes B-cells to produce antibodies more efficiently.
Hover, before the T-4 cell can recognize antigen, and begin this cascade of event which keep us healthy, if must first receive its programming form the thymus gland.
Thymus Gland, Its
Function and How Thymic Peptides Work
When small animals have their thymus removed (thymectomy), they experience a profound "wasting disease". The wasting syndrome is characterized by an increased incidence of infection and cancer (immune suppression, failure to grow, allergies, neuromuscular paralysis , and auto immune diseases (immune dysfunction). Greater susceptibility to infection and cancer was shown to be directly attributable to a dramatic decrease i peripheral blood lymphocytes (lymphopenia). Rearing the animal in a sterile environment prevented the increased incidence of infection and cancer but did not eliminate all of the symptoms caused by thymectomy.
In 1964 (2) it was demonstrated that hormone-like factors from thymus tissue could prevent many of the manifestations of the wasting syndrome caused by thymectomy. This research suggested that the thymus gland produces substances that are important to the development of the immune system. Although the relationship of this observation and the other wasting syndrome symptoms were not yet understood, the importance of the thymus gland was beginning to b revealed.
Once it was discovered that the thymus produces these hormone-like factors, several groups of scientists (3,4,5) began trying to extract and purify the material from thymus glands or serum. The model for this research was the preparation of insulin for therapeutic use in diabetes. Since the thymus produces extremely small quantities of the factors, researchers require large numbers of thymus glands or liters of serum to biochemically extract small amounts of active materials. This approach was met with limited success (6,7).
This research brought forth Thymosin in 1967 (3), the first of many peptides (small protein fragments) to be extracted and extensively studies. Thymosin fraction V is from bovine thymus and is a mixture of thirty or more peptides. An active component, one which had biological activity was isolated from this mixture. It is a 28 amino acid fragment of the extract called Thymosin Alpha 1. It displayed a variety of immune stimulatory properties in the laboratory, and has been useful clinically as a treatment for hepatitis B in combination with alpha-interferon.
A number of other peptide fragments have been extracted from calf or pig thymus, of from human serum. These include thymopoietin, thymulin, and thymic humoral factor (THF). These small peptides are thought to be a fragment of much larger molecules which have been localized in the stromal cells of the thymus. Even though most of these extracts exhibit some level of biological activity and tens of millions of dollars have been spent for clinic trials over the last 30 years, only Thymosin Alpha 1 has shown marginal effectiveness in the clinic.
Despite the modest clinical success of the fragmented thymic extracts, the research has indicated that the thymic proteins are produced by the epithelial cells of the thymus gland (8). During this same period, other research showed that there are two types of lymphocytes; T-lymphocytes (T-cells) which are thymus derived, hence the (T) for thymus and B-lymphocytes (B-cells) which are derived from the bone marrow, hence the (B) from bone marrow. B-cells are antibody-producing cells which fight bacteria, and T-cells are the primary protection against viral infections and cancer. Malfunctioning B-cells are involved in immune dysfunction and many auto immune diseases. Auto immune diseases are caused by the immune system attacking the body's own tissues. Arthritis, multiple sclerosis, muscular dystrophy, lupus erythematosus, and possibly juvenile onset diabetes are auto immune diseases. By 1971 it had realized that the T-cells regulated the reactivity of the B-cells. Recognition of the T-cells regulatory function in the immune system was important in bringing into focus the vital role of thymic peptides. Research published in 1982 and 1984 (9,10) brought proof of thymus function for the first time by assembling the various pieces of the puzzle.
Research centered on the theory that the thymus gland is central to proper immune function because it produces peptides in the epithelium that activate T-cells which in turn promote immunity.T-cells also regulate b-cells to produce antibodies for fighting infection, and further tell B-cells not to attack self tissue. Epithelial cells had been difficult to maintain in continuous culture in the laboratory, presenting a technological roadblock to isolating a specific thymic peptide for testing this theory.
Dr. Terry Beardsley overcame that technical roadblock in 1983 (9) by establishing a cloned line of thymic epithelial (TEPI) cells and several human cell lines. From this cell culture, he purified a specific protein which demonstrated immune stimulatory properties to those previously obtained by extra ts. However similar the results, TEPI showed a dramatically greater immune stimulatory effect that the extracts. The reason TEPI is so much more powerful is that it is derived from live cells and purified by a gentle biological method producing a natural intact protein. TEPI also known at Thymic Protein A is a 500 amino acid chain and is produced by Dr. Beardsley's cell line in exactly the same form as it is produced by the thymus in the body.
Later, Dr. Ester Hayes in collaboration with Dr. Beardsley demonstrated that this same protein is produced by the human thymus (10). They transplanted human thymus epithelial cells into the renal capsule of mice which had no thymus gland. the mice then demonstrated an immune response by living outside a sterile environment without developing infection. Additionally, the mice showed no sign of rejection of the transplant. No rejection of the transplanted tissue is an indication that the protein produced by the human thymus is so close to the mouse protein so as to be indistinguishable. Since this discovery, research has been concentrated in animal models of immunodeficincy, cancer, and infectious disease. Recently a small study was begun in humans infected with HIV. The preliminary results parallel those seen in animal models, which are the restoration of immune response as demonstrated by resolution of infection, increases in WBC, lymphocytes, T-cells, and other blood parameters. Recent clinical trials in humans infected with HCV demonstrated that using 3 doses per day gave significant immune system stimulation, and lowered viral loads.
It is theorized that replacement of vital thymus peptides can replace those missing due to atrophy of the thymus brought on by the aging process in much the same way diabetics use insulin. The technology now exists to produce these proteins in their natural intact state. Reintroduction of them in adult humans could have a profound effect on the aging process by restoring the bodies natural ability to defend itself from disease. the thymus gland produces dozens of these proteins and each one may have a specific purpose in human health and aging.
The Immune System is so complex in its relationships to organs, glands, and cells, immune dysfunction and suppression can have a number of different causes. But because the thymus gland plays such a pivotal and important role in generating and regulating immune response, and we are all subject to atrophy of the thymus due to aging, disease and radiation, chemicals, chronic disease or trauma, etc., a large portion of immune dysfunction and/or suppression is due to thymus deficiency.
Physicians have always treated deficiencies involving the thyroid gland, the pancreas, adrenal gland, etc. with physiologic replacement. Indeed the theory has been, "If a gland dries up, replace it". so, why not replace thymus proteins when the thymus gland dries up?
A Case for Replacements
It is therefore logical that since supplying whole thymus in a processed and fragmented from helps with thymus deficiencies, it would be so much more effective to supply a purified single thymus protein which is still biologically active.
This specific protein has been assayed chemically and in animal models fro the production of Interleukin 2. Interleukin 2 production by T-4 cells is the benchmark measurement for T-cell maturity and initiation of immune response. The protein is routinely tested in a Murine model for the suppression of flu virus, which further demonstrates the initiation of the cascade of events which results in immune response to specific pathogen (Cell Mediated Immune Response).
A trial with 22 cars infected with Feline Immunodefficiency Virus (FIV) concluded that this protein enhances immune response as measured by clinical and laboratory parameters. Immune response is demonstrated by response to infectious agents measured serologically, diminished disease symptoms, survival, and lymphocyte values.
An experiment published in The Journal of Immunology and Immunopathology in 1984 proved that this protein is conserved among species. The experiment entailed transplace of human thymus cells which produce this protein, into the renal capsule of athymic (nude) mice. Because the mice have no thymus, they have no immunity and must be kept in a sterile environment.
After the transplant, the mice demonstrated immune response outside the sterile environment and did not exhibit any rejection of the transplanted human tissue. This demonstrated that the protein induced cell mediated immunity in the mice and the restored immune system of the mice did not recognize the transplant as foreign. If the protein from the human tissue "looked" foreign to the mouse immune system, there would be massive immune response to that tissue. The absence of rejection proves that the human thymus protein is identical or so nearly identical to the mouse thymus protein that it is accepted as self. Being conserved among species is important because ingesting foreign protein can cause an antibody response, and in time cause the feign protein to have no effect.
Thymic Protein A
By age 40 to 45, most people lack proper thymus function, and therefore they lack complete immune function. You can replace this vital thymus protein by using Thymic Protein A everyday. In fact Thymic Protein A was proven as an immune stimulant and viral suppressor in laboratory tests conducted by the National institutes of Health. No other thymus product or extract has been proven to perform these functions because Thymic Protein A is the only thymus product which is a whole biomolecule and is conserved among species.
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