Promoting Health " NOT" Managing Disease

Table of Contents

The Immune System
The Innate Immune System
Killer Cells
The Acquired Immune System
The Thymus and Cytotoxic T Cell Development.
Antibodies
Introduction What is Transfer Factor?
Benefits of transfer factor.
Sources and Safety of Transfer Factor Blood.
Colostrum
Safety
Dietary Supplements
Immunological Agents Found in Colostrum Transfer Factor
Antibody (Immunoglobulin) Supplements.
Immune Modulator
summary
endnotes

INTRODUCTION
Our health and quality of life are directly influenced by the vigor of our immune system-an intricate, interrelated defensive force made up of a trillion cells.5 Today many factors contribute to the general weakening of our body's defenses. By examining the nature of the immune system and considering the explosion of recent research on natural agents that can potentially save lives, we can improve our quality of health and protect ourselves from an increasingly dangerous environment.

THE IMMUNE SYSTEM 6,7,8
The ability to protect us is both instinctive and learned. Our untrained, instinctive responses are our first defense against outside threats. Just as our instincts protect us from physical threats, our immune system inherently responds to microbial threats. This action of the immune system is called innate response. The extent of this response, however, varies according to the strength and conditioning of the immune system. A conditioned immune system produces a stronger response to a given threat than a weak or naive system. If the innate immune reaction is adequate, no additional response by the immune system is necessary.

Many times, however, our innate immune ability is insufficient against the variety of microbes we encounter daily. In these cases, our immune system has the ability to learn new skills and construct new tools to deal with these microbial invaders. These immune responses are called adaptive or acquired responses.

You may be familiar with the terms "T cells" and "antibodies." These aspects of the immune system are involved in adaptive response. Once we are exposed to an infectious agent, our bodies destroy that agent by trying to identify it and react to it. This process takes about ten to fourteen days. After we have successfully dealt with an infection, our immune system retains a memory of what it has learned about this particular microbial culprit so that the body is prepared if it attacks again. Typically, we are not even aware of the subsequent exposures to the microbe since our immune system's response is so rapid and overwhelming that the microbe has no opportunity to grow effectively. This adaptive response is the result of acquired immunity. This immune response is slow but normally very effective.

Just as our innate physical abilities determine the rate at and extent to which we can develop athletic expertise, so too our innate immunity greatly determines our ability to effectively develop adaptive immune response. Both response systems help to determine the level of health we have, and both are necessary to keep us healthy. By examining how the immune system uses both innate and adaptive responses, we can better understand how important the immune system is to preserving our health and what we can do to support a strong immune system by using supplements.

The Innate Immune System
Cells of the innate immune system (e.g. natural killer or NK cells) are first-line defenders against cancer and infectious disease.9 It is made up of various receptors and enzymes as well as the antiviral properties of interferon. The innate response system is characterized by the fact that it does not require prior exposure to an infectious agent.10 Further, the intensity of the innate response does not change when the system is repeatedly exposed to the same agent. Innate response works instead by recognizing distinct patterns in microorganisms and reacting to them.11,12 Pattern recognition is inherent and does not depend on its exposure to or familiarity with the microbial agent.

There are remarkable parallels in the innate immune systems of widely separated organisms, indicating that these ancient defense systems are essential to survival.13 In the past, the innate immunity of vertebrates has been considered archaic and obsolete, but today the innate immune system is regarded as essential to the function of adaptive immunity. In fact, the innate immune response appears to dictate the efficiency of acquired immune response.14,15,16,17,18 It is now generally accepted that the innate immune system initiates and improves the slower but more specific acquired immune response.19

Killer Cells.
The main function of immune cells like cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells is the killing of damaged or infected cells. CLTs receive their initial training in the thymus gland, which is part of the adaptive immune system and will be discussed later. However, NK cells, as mentioned earlier, are part of the innate response. They target cells that are missing the self-marker that identifies a cell as one of our own.25 Foreign cells do not have such self-markers, and many cancer cells have lost their self-markers. Cells without self markers are attacked by NK cells, while normal cells with high levels of self markers are intentionally spared from NK cell attack.26

The young, the old and the stressed are more susceptible to immunological breakdown. Augmenting NK cell activity may be critical in strengthening immunity in members of these groups. The differences in individual susceptibility to cancer are a clear indication of differences in immune system efficiencies among groups of people. For example, cancer is the second leading cause of death in children (after accidents) and is more prevalent in the first five years of life than in the subsequent ten. Laboratory findings indicate that the young may have a reduced resistance toward cancer because of their diminished NK activity.29

Human immune function also undergoes adverse changes with aging. T cells, which have a central role in cellular immunity, show the largest age-related differences in distribution and function. These differences can largely be attributed to the loss of thymus activity.30 NK cells are also affected. In fact, NK cells from elderly people show a decreased ability to multiply when stimulated and demonstrate an impaired killing capacity.31

Stress also affects NK cell activity. It appears that specific immune dysfunctions are associated with chronic stress.32 For example, stress due to injury suppresses NK cell activity,33 while inappropriate psychological reactions to stress can lead to disruption of immunity.34 Continuous stress reduces NK activity and allows tumors to grow faster.35

Low levels of NK cells have also been reported in a significant proportion of chronic fatigue immune dysfunction syndrome (CFIDS) cases.36 Familial CFIDS is associated with persistently low NK activity. This phenomenon may be the result of a genetic flaw that weakens immune response, predisposing the individuals to CFIDS.37 Individuals with low NK cell activity also tend to experience more severe forms of CFIDS.38

NK studies are ongoing. The therapeutic use of biologic response modifiers capable of manipulating NK cell activity in diseases like cancer and AIDS is being actively researched.39 Enhancing NK cell activity to counteract the immunological effects of immaturity, aging, stress and CFIDS should also be actively researched. NK cells are major facilitators of innate resistance to protozoan parasites,40 and without functionally efficient NK cells, other cells of the innate immune system are not optimally activated.41 In this light, certain dietary supplements that enhance NK cell activity may be beneficial.

The Acquired Immune System
Acquired immunity is the result of immune system adaptation to new pathogens that have invaded the body. In order to adapt to these newly introduced threats, the immune system must first recognize the threat, then develop a set of specialized tools and finally, maintain a long-term memory of the organism to protect against possible reinfection. Four critical aspects of acquired immune response are essential to its proper function: (1) the thymus gland and T cell development, (2) antibodies, (3) cytokines and (4) transfer factor.

The Thymus and T Cell Development.
The education of immune cells can be compared to a school system having grammar school, college and graduate level training. The thymus gland is the grammar and prep school for three groups of immune cells, and because of the involvement of the thymus; these cells are called T cells. They include helper T cells, suppressor T cells and cytotoxic T cells (most often called cytotoxic T lymphocytes).

Each type of T cell has its own particular function. Helper T cells assist the other immune system cells in performing their important functions. Suppressor T cells control immune response and keep the immune system from overreacting. Both helper and suppressor T cells perform their function by working indirectly or through other immune cells. Cytotoxic T cells, however, act directly on offending cells. CTLs are programmed in the thymus to look for self-markers and foreign markers. A combination of markers on the same cell identifies it as one of the body's own cells that has been damaged.

The immune training functions of the thymus gland are weak in infants and increase in strength until puberty. After puberty, the thymus gland begins to shrink and continues to diminish in size and effectiveness throughout the rest of our lives. The deterioration of the thymus, in terms of the immune system, is like the weakening of the school system. The reduced training of the T cells by the aging thymus is thought to be responsible for the immune deficiencies that develop during aging.42

The thymus also produces several hormonelike factors (thymosin alpha 1, thymulin and thymopoietin) that have been reported to help T cells maintain their immunological commitments. These thymic influences decline with age and are associated with "thymic menopause"- or ineffective T cell responses that contribute to the development of diseases in the elderly.43 To explain further, it is the job of the thymus to help us react against foreign cells and not against our own normal cells. As the thymus shrinks the body's normal immune response to foreign cells weakens, while the autoimmune attacks on our own tissues becomes stronger. This situation is called the aging paradox.44

Without a strong primary and secondary school system, many children have neither the math or language skills to adequately understand the instructions given to them further along in their schooling. Similarly, incompetent thymic training produces T cells that are unable to adequately interpret the immunological messages they receive from their environment. In addition, stress from a variety of sources-poor nutrition, emotional strain, infectious assault, cancer or injury-also weakens the immune system's ability to learn new strategies.

Antibodies.
Antibodies are protein molecules produced by B cells (white blood cells derived from bone marrow) that act as the primary force of the immune system. Antibodies attach themselves to foreign markers on cells. They are uniquely shaped in order to combine with and then disable threatening antigens. Antibodies are also called immunoglobulins. The most important types of human antibodies are IgA (immunoglobulin A), IgE, IgG and IgM. Each of these has a specific function in immune response.

Macrophages ("big eaters") are large immune cells that engulf and selectively "degrade" (break down) foreign, dead or damaged cells. If the engulfed cell is infected or malignant, the macrophage retains intact any new foreign sequences that can be used as antigens-recognition markers used by the immune system to stimulate antibody production. Macrophages then act as antigen-presenting cells, which means that the macrophages present the newly discovered antigens in a form T cells can recognize. The immune system can then initiate an adaptive immune response to eliminate the foreign or cancerous cell threat. (Dendritic cells also can serve as antigen presenting cells, especially in cases of cancer).45

Memory T cells and B cells are produced by the immune system as a means of storing the immunological information that has been gained by the host. Because of its memory capacity, the response of the immune system during the second exposure is usually so effective that we are not even aware that we have been re-exposed.

TRANSFER FACTOR
Introduction What is Transfer Factor?
If the thymus gland can be compared to grammar school and prep school, then transfer factor can be compared to collegiate and graduate level training for the immune system. The importance of more sophisticated, immunological education should not be underestimated. Discovered in the late 1940's by Dr. H. Sherwood Lawrence, transfer factor has emerged as an important element in the current search for alternative disease and infection fighters.46 While studying tuberculosis, he found that the immunity of one individual could be transferred to another by using small molecules. These "transfer factors," as he called them, could transfer immunity form a competent immune system to a less able system by using low molecular weight extracts obtained from white blood cells.

Scientists later found transfer factors to be universally effective, regardless of the differences between the species of the donor and recipient. This aspect of transfer factors is partly explained by this core scientific belief: the more essential a material or structure is to living organisms, the more common it is to see this material or structure throughout living systems. Transfer factors are essential components of even the most primitive immune systems.47

One essential principle of the immune system is that it must be able to respond quickly and specifically, while not exhausting itself by overresponding and attacking normal tissue. Transfer factor preparations consist of three identifiable fractions named by their discovered effects on the immune system-inducer, antigen specific, and suppressor.48 The inducer fraction triggers a general state of readiness in the immune system. The antigen-specific fraction is an array (arrangement) of critical tags used by the immune system to identify a host of enemy microbes. Meanwhile, the suppressor fraction keeps the immune system from focusing all its strength on a defeated infection and ignoring new microbial threats. It is responsible for controlling immune overreactions that can cause autoimmune disorders.

Each fraction (inducer, antigen specific and suppressor) improves one or more aspects of the adaptive ability of the immune system. As the product of a competent immune system, transfer factor teaches a less competent immune system how to better protect itself. For example, transfer factors are passed from mammalian mothers to their offspring through the colostrum in their milk.

A mother's gift of transfer factor greatly improves the immunity of her offspring and many times means the difference between life and death for the newborn. In fact, because the modern dairy cow is in such intimate microbial contact with her environment, she produces far more transfer factor than her calf needs. And so, although it was originally thought that transfer factor could only be transferred successfully through the blood, many now believe that colostrum in dairy milk is the best source of transfer factor. Harvesting the excess colostrum and isolating its transfer factor supply provides an abundant and beneficial source of transfer factor for human consumption.

Unlike antibodies that are large molecules, transfer factors are quite small.49,50 In fact, their small size helps to make them nonallergenic.51,52 And while antibodies are used up when they attach themselves to the offending cell or protein, transfer factors perform a different role. They are immune messenger molecules that educate and alert naive immune cells to an impending danger. In this regard, transfer factors perform a catalytic role in the immune system-triggering the effect without being consumed.53

Originally, transfer factor preparations were administered by injection.54 However, later studies showed that transfer factor was equally effective when taken orally.55 This observation is consistent with studies on the oral absorption of other peptides of similar size.56 In addition, as stated earlier, the nonspecific inducer and suppressor fractions of transfer factors are fully cross-compatible between species. The antigen-specific transfer factors, however, are each specific to a particular pathogen and these pathogens vary from species to species.

One might ask, then, if there is any reason humans should use antigen-specific transfer factors from other species. The relationship between human smallpox and cowpox infections is illustrative of antigen crossover-a term that describes what happens when two different pathogens share some of the same "antigenic fingerprints." Although the highly contagious and often fatal disease smallpox devastated many European and American communities in the 1700's, one subset of individuals seemed to survive the epidemics-milkmaids.

Milkmaids often contracted cowpox from infected animals during milking through a cut or other break in the skin. Milkmaids infected with cowpox usually followed a mild course of the disease that was resolved without much difficulty. It was then found that milkmaids who had contracted cowpox were immune to smallpox. In a classic, early inoculation experiment, Edward Jenner vaccinated a young boy with cowpox and then demonstrated that the child was protected from contracting smallpox. The relationship between smallpox and cowpox is a case of antigen crossover where the immune system will recognize two different pathogens after being exposed to either one.

Antigen crossover between these sets of human and bovine pathogens is highly likely. The antigen-specific, bovine transfer factors should therefore provide protection to humans against the corresponding human pathogens, resulting in milder course of disease.

Benefits of transfer factor.
The exciting benefits of transfer factors-the essence of the immunological message-could spark a revolution in medicine. The need for such a new weapon in our immune defense arsenal is clear. "Transfer factor has an important role to play in modern medicine which, from AIDS to Ebola, faces the emergence of new viruses or the resurfacing of old pathologies such as tuberculosis."57 Nevertheless there are always many who resist new ideas, regardless of their benefits.

Sources and Safety of Transfer Factor Blood.
Dr. Lawrence reported in 1949 that transfer factor could be prepared from blood. Human blood sources could include live donors or outdated blood from blood banks, but using human blood sources includes all of the hazards associated with blood transfusion, such as HIV and hepatitis. In addition, neither freshly drawn nor outdated blood from blood banks is an adequate source of commercial transfer factor. Slaughterhouses have also been used to supply blood, spleens and lymph nodes for production of transfer factor products.73 However, a third blood-based technology involves the use of leukocyte cell cultures to produce transfer factor.

Colostrum.
A more practical and popular source of transfer factor, however, does not come from blood sources. Colostrum, the first mammary secretion that a mother provides for her offspring immediately after birth, is a rich source of transfer factors.76 The most abundant source of colostrum comes from dairy cattle. As discussed earlier, transfer factor is composed of two nonspecific functions, induction and suppression, as well as a third antigen-specific function. The nonspecific functions have shown no species differences. The antigen-specific function may vary between species based upon their exposure and susceptibility to various pathogens and the antigenic similarity of the different pathogens.

Safety.
Transfer factor has an excellent safety record, and no adverse side effects associated with transfer factor have been reported, even when administered in extreme excess or over several years.51,52,53,65,77,78 Based on the discovery of transfer factors in both blood and colostrum, studies have shown that transfer factors are effective whether administered by injection or taken orally.55,79Infants and the elderly are the two groups most at risk for infection, and the naturally high levels of transfer factor in colostrum clearly indicate its intended use and safety for infants. Oral administration of transfer factor, in particular, is convenient and easily accepted by all age groups.80

In addition, over 3,000 papers have been written on transfer factor since it was first reported in 1949. Studies on the human use of transfer factor have shown how it can relieve unnecessary suffering simply and safely. For more complete examination of transfer factor and its benefits to human health, refer to my Woodland Health Series booklet Transfer Factor: Natural Immune Booster.

DIETARY SUPPLEMENTS
Since before recorded history, man has used dietary supplements to improve his health. Most of these supplements have been derived from plants with peculiar healing properties. Two of the oldest recorded medicinal supplementation codes are the Chinese codex from the Shang dynasty (ca.1766-1122 BC) and the Indian medical system Ayurveda, first recorded in the seventh century BC. In the Americas, Echinacea was used from Texas to Saskatchewan. The whole discipline of ethnopharmacology developed in order to capture and substantiate the folk medicine of cultures throughout the world.

And in fact, many of the oldest and most revered supplements have been found to strengthen the immune system. Plants, however, may not be the most ancient source of supplements for the immune system that were used by man. The oldest immunological supplement may in fact be found in the colostrum, provided by every mammalian mother who nurses her offspring.

Immunological Agents Found in Colostrum Transfer Factor.
The first milk of every mammalian mother naturally contains transfer factors that reflect her rich immunological experience.93 If the baby is allowed to nurse, initial immunity is rapidly established. This is nature's way of quickly educating a naive infant in the hazards of a microbe-infested world.94 On the other hand, infants who are not breast-fed consistently show a greater susceptibility to infections, allergies and childhood cancer.95,96,97

The nature of the modern diary cow is such that she has intimate microbial contact with her environment and produces far more colostrum (and therefore more transfer factor) than her calf needs. Since transfer factors are universally effective regardless of the differences between the species of the donor and the recipient, harvesting the excess colostrum and isolating the transfer factor provides a commercial source of transfer factor for human consumption.

Originally transfer factor preparations were administered by injection.98 Later studies, however, showed the transfer factor was also effective when taken orally.55 This observation is consistent with studies on oral absorption of other peptides of similar size.99 It is obvious that Nature intended colostral transfer factors to be taken orally.

Transfer factor, as an extract of colostrum, is generally recognized as safe (GRAS) and is considered to have safety profile similar to milk. Although lactose intolerance due to milk ingestion is present to a degree in many populations, even persons who are clinically lactose intolerant can tolerate between two and six grams of lactose,100 as a result of colonic bacterial degradation of lactose.101 Unlike large-molecule antibodies, transfer factors are quite small.102,103 The small size of transfer factors helps to make them non-allergenic.51,52 In fact, it is actually the immunoglobulins (antibodies) found in bovine colostrum that are the source of most cow-milk allergies in humans.104,105

Antibody (Immunoglobulin) Supplements.
Oral ingestion of antibodies is naturally observed in mammals when the mother provides colostrum to her offspring. Studies have shown that antibodies from colostrum are absorbed intact into the bloodstream of newborns. Absorption of intact antibodies, however, usually ends within twenty-four hours of the first feeding, due to the maturation of the infant's intestinal tract.106 Two features enable the success of antibody transfer. First, the mother and infant are of the same species and so no antibody rejection occurs; and second, the recipient is an infant with an immature and highly permeable digestive system.

Oral administration of antibodies to adults leads to rapid degradation of the antibodies by stomach acid and intestinal enzymes. Only when both stomach acid and intestinal enzymes can be neutralized will maximum benefit be obtained from orally administered antibodies.107 Antibodies from colostrum are not well absorbed except in newborns as noted above, though oral ingestion of antibodies is most effective in treating diarrhea.108 In this case, no absorption of the intact antibodies is required since the troublesome agent is in the intestinal tract.

Intravenous antibody therapy has been examined experimentally since the 1930's.109 It was found that any nonhuman antibody was rapidly rejected by the human immune system, often leading to a severe side reaction called "serum sickness."110 Because of this reaction, intravenous administration of antibodies from different species was largely abandoned. In addition, many of the antibody benefits are dependent on the proper binding of the antibody, not only to the infectious agent but also to various immune cells. In the latter case, antibodies from one species are totally ineffective in communicating with immune cells of a different species.

Immune Modulator
Immune cells can be separated into different classes of cells. If a substance produces differential responses from different classes of immune cells, it indicates that the substance is an immune modulator rather that a strict suppressor or immune stimulant. Strict immune stimulation can lead to immune system exhaustion and strict immune suppression can lead to immune compromise and ineffectiveness. Transfer factor and the transfer factor combination both act as immune modulators and not solely as immune stimulators. Both inducer and suppressor fractions are found in well-made transfer factor preparations. The demonstration of different effects on various immune cell populations is in keeping with these differential transfer factor functions. The combination product, Transfer Factor PlusTM, also retained an immune modulatory rather than a strict immune stimulatory effect. This indicates the dominant role of transfer factor in the combination product Transfer Factor PlusTM.

SUMMARY
The immune system is an elegant and sophisticated network of cells and molecules that strive constantly to maintain our health and physical integrity against an onslaught of increasingly resistant microbial invaders. These microbes and our own cancer cells use an array of techniques to evade or subvert our immune responses. Dietary supplementation discussed in this booklet may help us to attain an immunological advantage over invading microbes and invasive cancers.

Thymic factors have been use to regain immune competence by supporting diminished thymic function. Transfer factors exert a trifold impact on the immune cells through inducer, suppressor and antigen-specific actions via helper and suppressor T cells, and Cytotoxic T Lymphocytes respectively, using entirely different mechanisms. Transfer factor exhibits its beneficial effects only in the presence of immune cells.

Both the antimicrobial and radioprotective effects of acemanannan depend on the presence of the immune system. Beta-glucan has an extensively documented immunological benefit. Recent research has clarified much of the earlier therapeutic confusion and has rational basis for the effective use of beta-gulcan as a biological agent. The combination of acemanannan and beta-glucan appears to provide a greater immunological impact that either agent alone. Inositol hexaphosphate (IP6) appears to act by a different mechanism that results in improved intracellular control of malignant cell. These ingredients are found in the combination product.

The combination of these agents has demonstrated a synergistic impact on NK cell activity with no measurable toxicity, even at excessively high concentrations. These facts open up the potential for enhanced nutritional support for an optimally functioning immune system.

ENDNOTES
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