Anatomy and Physiology of the Immune System, Part 1

Written by: Jon Barron 1999-2011 The Baseline of Health Foundation I devoted a full chapter in Lessons from the Miracle Doctors [2] to an exploration of the immune system from an alternative health perspective, but today I want to start a series of newsletters that will expand on that work and fill in some of the missing details. To be sure, it would be easy to devote an entire book to the immune system -- both because of its complexity and its importance -- but for now, a series of newsletters will have to do. Your immune system plays two vital roles in your body. First of all, it responds to foreign organisms that gain access to your body by producing antibodies and stimulating specialized cells that destroy the organisms or neutralize their toxic byproducts. In this manner, it defends against foreign invaders, including: germs, viruses, bacteria, fungi, and parasites. But it also stands guard over the cells of your body to ensure that they do not become abnormal or degenerate. Normally, your body produces anywhere from 100 to 10,000 abnormal cells a day in your body -- produced as part of the normal metabolic processes, or as the result of exposure to environmental toxins or nutritional deficiencies. But if your immune system is functioning properly, it can identify each and every one of those cells and eliminate them before they can do any harm. All in all, understanding how your immune system works and how to optimize it, while at the same time keeping it in balance so it does not run out of control, turn on you, and attack your own body, is essential to good healthif not your very life. Your immune system In many ways, your immune system is the most awesome system in your body, easily rivaling the brain in terms of complexity, subtlety, and "self-awareness." As I mentioned a moment ago, your immune system is capable of identifying every single cell in your body and recognizing those that are friendly and belonging to your "self." Conversely, it is also capable of singling out and identifying every single foreign invader that manages to make its way into your body -- ranging from bacteria and viruses to fungi and parasites -- and treating them as "non-self." (Later on we will explore exactly how it accomplishes this remarkable feat.) Once it has identified an invader, your immune system then quickly develops a customized series of defensive weapons that specifically target the invader's weak link. It then begins building cellular factories that produce these weapons en masse, in quantities sufficient to totally overwhelm and crush the invader. Then, once the invader has been defeated, the immune system has the awareness to "shut itself down" until needed at a later date. As amazing as all of this sounds, we haven't yet come to the three most awe inspiring aspects of the immune system -- the ones that highlight its intelligence.

First, once it has defeated an invader, your immune system has the ability to "remember" that invader and the defense that was used to defeat it. If that invader ever makes another appearance, even years later, your immune system can launch its defense instantly -- and at a level 1,000 times stronger than when the invader first appeared. In addition, your immune system can identify when a cell in your body has changed, has "gone over to the enemy" as it were -- when it has turned from "self" into "non-self." This is a stunning level of sophistication. Out of the trillions of cells in your body, your immune system can tell when a single one has mutated and become cancerous -- and, in many cases, move in and destroy it before it can do any harm. In fact, it does this thousands of times a day, without missing a single mutant cellwe hope. But most amazing of all, your immune system is in total communication with each and every part of itself. "So, what's the big deal," you might ask? "The brain does the same thing." Yes, but remember, unlike the brain, the trillion+ cells of the immune system are not in physical contact with each other. To paraphrase Albert Einstein, "At its core, the immune system resembles nothing so much as a great thought." And for good measure, your immune system is also in constant contact with your brain, not to mention every single cell in your body -- not only receiving information from those cells, but also sending information and commands back to them so as to marshal systems and organs outside itself as required. To put it simply, your immune system is awe inspiring! The anatomy of the immune system

Before we even begin to look at the immune system, we need to define what we're talking about when we refer to the immune system, which is not quite as simple as it might first seem and is actually open to some debate. Generally speaking, though, the body's immune system is comprised of those cells and organs that

contribute to the body's active response against foreign invaders and self-generated rogue cells -- "active" being the operative word. The immune system, then, excludes non-specific defenses -- primarily physical barriers -- such as the skin, respiratory tract, and lining of the intestine. The inside of the nose, for example, is lined with mucous to capture pollen and dust and prevent them from entering the body before they can become a problem. That is an immune function, but since it is both passive and non-specific, it's not counted as part of the immune system. But what about the 100 trillion beneficial bacteria that line every square inch of a healthy intestinal tract, from your mouth to your anus? They not only provide a passive barrier to invading pathogens, but a number of them actively kill those same pathogens. Others produce immune-boosting biochemicals such as transfer factor and lactoferrin. L. plantarum, for example, has the ability to eliminate thousands of species of pathogenic bacteria. That's a pretty "active" immune function. And then there's acidophilus. It can produce a number of powerful antimicrobial compounds in the gut (including acidolin,1 and bacteriocins such as acidophilin and lactocidin.2 If present, beneficial bacteria [3] in your intestinal tract can account for 60-70% of your immune system's activity. Nevertheless, in accordance with standard medical texts, for the purposes of these newsletters, we will consider them outside our definition of the core immune system proper. However, that still leaves the Complementary Immune System, comprised of a series of cascading enzymes, which although many medical texts do not include, we willand we'll discuss it later. For now, though, let's focus on those parts of the immune system that are specific, wide-ranging, and have long term memory, which is the standard medical definition of active immunity. In addition, as we discussed earlier, the active immune system can distinguish "self" from "non-self" with great accuracy and subtlety. An example of its subtlety is that despite its tendency to reject anything that is foreign, it is, nevertheless, extremely tolerant of foreign substances that it encounters during embryologic development and early infancy. That means that if you expose a fetus to a foreign body during development, it will not reject it, but rather recognize it as "self" from that point forward. Why is this so crucial? Because it allows the mother to pass natural antibodies to the fetus across the placenta, or to the baby in breast milk, thus helping to protect the child with the mother's immunity before the baby builds its own immune function, not to mention facilitating the actual building of the child's immune system. This, of course, is crucial to the child's survival.

The anatomy of the immune system

All blood cells, both red and white, begin as stem cells in your bone marrow. These undifferentiated cells begin to assume individual characteristics and become either red cells (the oxygen carriers) or white cells (the cells of the immune system). Further differentiation divides the white cells (also called leukocytes) into four main types of cells: Lymphocytes T-cells Helper cells Natural killer (NK) cytotoxic T-cells Suppressor T-cells Memory T-cells B-cells Phagocytes Granulocytes Dendritic cells. Let's explore them in more detail. Lymphocytes Lymphocytes are white blood cells that detect and destroy foreign invaders in various ways. They serve as the key operatives of the immune system. In a healthy body, not under attack, they number about one trillion. There are three main classes of lymphocytes: T-cells, B cells and natural killer (NK) cells. Under a microscope, T and B cells are indistinguishable from each other. It wasn't until specific antibody testing procedures were developed that scientists were able to differentiate between them. NK cells are easily spotted because they are noticeably larger than either T or B cells.

T-cells T-cells work primarily through what is known as cell mediated immunity, which is another way of saying that they do not instantly attack invaders on their own authority like antibodies do, but rather require other cells to activate/mediate their response. In addition, they work not so much by "directly" attacking invaders but by attacking cells that have been infected by invaders and inside which the invaders are hiding. In other words, T-cells primarily defend against viruses that have taken up residence in host cells and cells that have turned malignant. This is in contrast to B-cells and antibodies that take on invaders that work out in the open in your bodily fluids -- most notably bacteria. Another difference between T-cells and other cells of the immune system is that Tcells are smarter than the other guys. They've been to school, as it were. When T-cells leave the bone marrow, they have no functioning TCRs (T-cell receptors) and are virtually identical to each other, and essentially non-functional. In fact, they are called pre-T-cells, or pre-TCR T-cells. But then they go to "school" in the thymus, which is where they migrate to after leaving the bone marrow. The thymus is a small fatty gland located under the collar bone. It "curls up" after childhood and is difficult to find in adults, but it's still there. Incidentally, the "T" in T-cells refers to the fact that they mature in the thymus. While in the thymus, they learn two things. First, they are educated (programmed by certain thymic proteins) in how to distinguish between the cells of the body and invading cells, and how to distinguish between normal healthy cells and mutated rogue cells. This is where they learn to distinguish between "self" and "non-self." T-cells that cannot make this distinction are eliminated so that they do not make their way into the body and begin attacking it.

In addition, the pre-T-cells are also exposed to proteins associated with virtually every invader that the body has ever encountered in its existence --or that has been passed on to it by its mother. Like young children that have very malleable minds, the DNA associated with the non-functioning T-cell receptors is very malleable and can be easily rearranged in multiple variations, thereby creating millions of different T-cells with millions of different TCRs. TCRs, by the way, are protein molecules on the surface of T-cells that are responsible for recognizing specific protein molecules found on the surface of each different invading antigen. Each and every one of these "new" TCRs is now functional in that it can respond to each and every one of the invaders whose protein was used to train the T-cell. Those cells that fail this part of training (that have unstable TCRs) are eliminated. But those that survive differentiate into either CD4+ or CD8+ T-cells depending on which class of antigen they are trained to recognize. If their TCR recognizes an MHC class I antigen (as found on nucleated cells, such as cells infected with a virus), they become T8 cells. If their TCR recognizes an MHC class II antigen (as found on other immune cells such as macrophages, T8 cells, B cells and dendritic cells), they become T4 cells. This is important because MHC proteins act as "signposts" that serve to alert the immune system if "non-self" material, such as a virus, is present inside a cell. They achieve this by displaying fragmented pieces or antigens on the host cell's surface. Once matured in the thymus, every T-cell carries a distinctive molecule on its surface that affects how it behaves. This is the T-cell receptor that we've already talked about. T-cell receptors are actually protein molecules that function as "locks" for the MHC "keys" found on the surface of antigens, and other cells of the immune system. (We will discuss this in more detail later.) Antigens, by the way, are foreign molecules or substances that provoke an immune response from the body by virtue of specific geometric arrangements (antigenic determinants) on their molecular surfaces. An antigen could be a grain of pollen, a speck of dust, a bacterium, a blood cell, or a simple molecule. The bottom line is that something on the molecular surface of the antigen is recognized by the immune system as "nonself." So once again, the MHC molecule "keys" tell the immune system "locks" what's inside the antigen -- whether it's friend or foe -- according to what molecular lock on the T-cell's surface the key fits into. It should be noted, however, if we wish to press our lock and key analogy a little further, that although TCRs are unique and number in the millions, we're nevertheless talking about a low security skeleton key system here as opposed to a high security vault key. That is to say, despite the tendency to specificity, many different T-cell receptors recognize the same antigen, and many antigens are recognized by the same TCR. The TCRs are named after the proteins they present on the surface of the T-cells on which they reside according to a naming convention referred to as the "cluster of

differentiation" (CD) protocol. Thus a cell that carries a cluster of differentiation 4 protein on its surface is called a CD4+ T-cell (aka a T4 cell). If it carries an 8 protein, it is called a CD8+ cell (aka a T8 cell). Although there are a number of different CD cells (CD1, 2, 3, and 17, for example), the two primary types of Tcells are CD4+ and CD8+. T4 cells are known as helper T-cells because they don't attack invaders themselves, but rather identify foreign invaders, activate B-cells, other T-cells, natural killer (NK) cells, and macrophages to attack the invader. T-8 cells, on the other hand, are known as cytotoxic T-cells (also called "killer cells"), which -- once activated by T4 cells -- attack and destroy rogue mutated cells in the body or cells that have been invaded by viruses and compromised. Because this is a two-step process that requires the T4 cells to mediate both the recognition of an invader and the subsequent attack on that invader by the killer cell, it is often referred to as cell-mediated immunity.

Also, as I mentioned earlier, T-cells defend against intracellular pathogens -- things that happen inside other cells or by other cells. Viruses, for example, are intracellular pathogens. They work inside cells. Until a virus implants itself inside the cells of your body, it can neither replicate nor do any harm. Fortunately, even though hidden inside your body's own cells, the viruses leave traces of themselves on your cells' surfaces, which usually allow your immune system to track the viruses down. Additionally, some cancers, which also use your own body's cells to harm you, present protein markers on their cell surfaces, just like viruses, that allow your immune system to perceive them as "non-self" foreign bodies (much like virus infected cells) and thus marked for destructionif your immune system is functioning properly. On a related note, tissue transplants (lung, heart, kidney, etc.) are also viewed as intracellular foreign bodies -- unless coming from an identical twin -- and thus

subject to an all-out attack by the body's T-cells. This can quickly lead to rejection of the transplanted organ. That's why transplant recipients require immunosuppressants for the rest of their lives to prevent such an attack. That said, even if you use immunosuppressants, there will be a continual low level attack on the transplanted organ that over time can lead to the degradation of the transplanted organ. But immunosuppressants can push that date out many, many years. It should be noted that we don't store a lot of T-cells, just a few of each kind. Storage areas include the spleen, liver, and Peyer's patches in the intestinal tract. The T-cells wait there, looking to see if they recognize the particular protein geometry of an invader they have been trained to identify and then react to it. Helper cells This is pretty much another name for T4 cells (CD4+). T4 cells are known as helper T-cells because they help activate the antibody-mediated immune response by identifying foreign invaders, then help activate B-cells, other T-cells, natural killer (NK) cells, and macrophages to attack the invader. In addition, T4 cells produce interlukin-2 to costimulate virtually all immune processes. Cytotoxic NK (natural killer) T-cells These are mainly T8 cells that have been activated by T4 cells and "transformed" into killer T-cells (AKA, Killer CD8+ T-cells). Remember that we mentioned earlier how the T-cell receptors on T4 cells are tuned to identify and locate other cells in the immune system in addition to "non-self" invaders? Well, NK T-cells are the reason why. T4 cells identify the invading threat and then hunt down T8 cells to transform them into killers to crush the invader. Once activated/transformed by the T4 cell, the T8 cell undergoes further growth and differentiation when stimulated by interleukin-2 released by the same T4 cell that locked onto it and activated it. This exponentially increases the number of NK cells programmed to identify a target antigen and then travel throughout the body in search of antigen-positive cells to destroy. This provides a failsafe two-step costimulation process for your immune system -- stimulation by direct contact with the T4 cell and stimulation by the interleukin-2 released by the same T4 cell. This two step process helps prevent the immune system from misfiring and attacking healthy cells in the body. This is so important that it's worth discussing in a little more detail. A car provides a useful metaphor for thinking about the way costimulators (interleukins, AKA cytokines) work. If antigens on foreign invaders are the "keys" that turn on the T-cells' engines, then costimulators, are like "putting the car into gear" after you turn the engine on. In the same way that you wouldn't want a car to jump forward the moment you turn the ignition key, you wouldn't want your immune system to jump into action until the nature of the invader was truly verified. In this sense, the interleukins serve as a failsafe backup mechanism.

The literal translation of interleukin is, "To speak between white cells." Once it has been determined that the threat registered by the T-cells is legitimate, the interleukins will communicate between the T4 and T8 cells to throw the immune system into action by up-regulating its activity. A question you might have at this point is, "Just exactly what are costimulators protecting against?" In simple terms, the failsafe system is required to make sure the body doesn't throw itself into an overly strong allergic reaction and possible anaphylactic shock. When the system doesn't work properly, we have exaggerated allergic responses to seemingly innocuous situations. This can sometimes even result in death. All of that said, after recognition of the invader and costimulation by interleukin, the T8 cells are sensitized and transformed into cytotoxic killer cells; after which, they then begin to clone themselves into millions and millions of identical killer cells with similar TCRs -- all primed to attack the new invader. Killer T-cells recognize specific "non-self" cells (primarily intracellular foreign invaders) and kill them by lysing (breaking apart) the compromised cells. They require direct contact to kill cells. Doctors call this the "kiss of death." The reason for this is that the CD8 key of the activated Cytotoxic T-cell has to directly insert itself into the specific Antigen-MHC-1 TCR protein complex on the compromised cell that it is trained to recognize. Once this lock and key mechanism attaches, matches, and inserts, it sets up a series of responses.

The Cytotoxic T-cell secretes a protein called perforin, which causes the invader's plasma membrane to blow holes in itself, thus causing the cells' contents to spew

out and the infected cell to die. If the invader is a virus that has taken up residence within the cell, killing the cell prevents the virus from reproducing. In addition, macrophages eat up any viruses that flow out from the broken cell (see below). NK cells secrete lymphotoxin, which kills enzyme systems in the invader. They secrete gamma interferon, which stimulates macrophages to eat foreign invaders. Thus any viruses that were released from inside the cells are now fully exposed and subject to destruction by the macrophages. (As we mentioned earlier, viruses are intracellular foreign invaders. They can't work, reproduce, or do damage by themselves. They are literally DNA surrounded by a protein coating. They have to take over another cell and its energy producing mechanisms in order to replicate and spread damage. Once a virus enters a human cell, in most cases, it is protected inside that cell. However, it will leave telltale traces of protein on the cell surface that will tell the immune system to no longer consider that cell as part of "self" and attack the cell in which it has taken up residence. Blowing apart that cell exposes the virus to the other elements of the immune system capable of destroying it. ) Once they have done their job killing a cell, cytotoxic (killer) T-cells can detach and find another invader -- thus killing again, and again, multiple times, before they are used up and die. Suppressor T-cells So what happens when the invader is destroyed? How does the immune system know the battle has been won, and that it's time to take a rest? That's where Suppressor T-cells come into play. These cells cause down-regulation of the immune response. Very little is known about them. But medical researchers do know that when the immune response has gone on long enough and that the invader has been defeated, suppressor cells somehow signal the rest of the immune system to ratchet down so that it doesn't start harming healthy cells. The bottom line is that we don't yet know how they do these things -- only that they do. It should be noted that some cancer cells have the ability to convince suppressor Tcells to tell the rest of the immune system to shut down prematurely so that the immune system won't attack the cancer cells -- thus allowing the cancer to spread unopposed. Very devious.Very nasty. Memory T-cells Once an invader is defeated, most of the active T4 and T8 cells dry up and disappear. However, the T4 cells produce a clone of themselves called Memory Helper T-cells, which can last a long, long time (anywhere from decades up until the day you die) to resist the next invasion of that specific antigen. This is an amazing advantage when you consider that building that first recognition response can take up to a week or ten days. That's a lot of time for an invader to have free rein in your body -- more than enough time to make you extremely sick, or even

kill you when faced with an aggressive invader. However, having Memory Helper T-cells in place cuts that time to just a matter of hours. Consider the example of a mother taking care of her child with measles. How does her previously acquired immunity prevent her from getting measles? Surprise! It actually doesn't. Every mother actually catches measles from her child no matter how many times she's been vaccinated or had measles herself. But because of her immune system's "memory" of measles, her immune system's response is so fast that she totally eradicates the invader before she even gets one single symptom. This is a really, really important point to understand about your immune system. Even if you have immunity, you're still going to get the disease, if the virus enters your body. The virus absolutely starts reproducing in your body, but the response is so fast that it kills the virus before it can ever really get started. It's gone before you ever even knew it was there. That's how immunity works. But it's not only the speed of the response that's increased, it's also the strength. The response triggered by memory cells during second exposure to an invader can be as much as a 1000 times stronger than the initial response. This is known as an anamnestic (or accelerated) response. And that's how a trained immune system protects you against a foreign invader -- virus, bacteria, fungus, whatever. And in fact, approximately one in every 200 immune systems can even protect against seemingly unprotectable viruses such as HIV AIDS [4]. Pretty amazing, not to mention being indicative of opportunities for optimizing your immune system through both natural and medical means. Conclusion That concludes our discussion of cell mediated immunity -- T-cell immunity, mediated by lymphocytes, interferon, and interleukins. In Part 2 of our series on the Immune System, we'll explore: Humoral immunity, which takes place in the blood. B cells, the primary agents of humoral immunity. Antibodies, the chief weapon of the humoral immune system. Phagocytes -- the "Sin Eaters" of the immune system. Granulocytes. Think of them as bounty hunters or hired guns. Dendritic cells. These are kind of like super heroes with special powers. Spiderman comes to mind. The organs of the immune system. And how to boost your immune system. In subsequent parts we'll also explore some of the diseases of the immune system, how to rebalance your immune system, Circulating Immune Complexes, the Complementary Immune System, how to give your immune system a break and directly kill invading pathogens, how your immune system communicates with

itself, the pros and cons of immunization, and how medical science is both helping and hurting the immune system.

1. Hamdan IY, Mikolajcik EM. "Acidolin: an antibiotic produced by Lactobacillus acidophilus." J Antibiot (Tokyo). 1974 Aug;27(8):631-6. <http://www.ncbi.nlm.nih.gov/pubmed/4373425> 2. Luc De Vuyst, Frdric Leroy. "Bacteriocins from Lactic Acid Bacteria: Production, Purification, and Food Applications." J MolMicrobiolBiotechnol 2007;13:194--199 <>

Anatomy and Physiology of the Immune System, Part 2 We explored the elite half of the immune system: cell-mediated immunity. These are the T-cells and Cytotoxic NK killer cells. To use a military analogy, these are the officers of the immune system -- those educated at West Point. In this issue, we explore humoral immunity, the grunts of the immune system, the draftees who man the front lines and do the bulk of the fighting. These are primarily the B-cells, antibodies, phagocytes, granulocytes, and dendritic cells. In poetic terms, these are Tennyson's "Six hundred."1 This is where millions and millions of "cellular soldiers" are thrown into battle and sacrificed in defense of your body. And frequently, this is where the battles of life and death are fought -- your life and death, that is. The word humoral is a throwback to the earliest days of medicine when doctors thought the body was regulated by four basic fluids called humors. Specifically, they thought that the body was filled with black bile, yellow bile, phlegm, and blood, and that illness occurred when these humors were out of balance. "Blood letting," was a common treatment used to put the humors back in balance by reducing excess blood, thus bringing the body back into balance.

Nowadays, when doctors refer to "humoral immunity," they're just talking about that part of the immune response that takes place within body fluids (notably blood and lymph), not inside body cells, which, as we saw in the last newsletter, is where cell-mediated immunity works. In other words, humoral immunity works

against extracellular pathogens in the blood and lymph -- most notably bacteria and viruses not yet in cells, or that have been forced out of cells by cytotoxic NK cells. Humoral (antibody-mediated) immunity Humoral immunity targets invaders directly. To clarify, cell-mediated immunity defends against viruses that have taken up residence inside host cells and are doing their dirty deeds while ensconced there, whereas humoral immune cells take on invaders (bacteria, inactive viruses, fungi, molds, etc.) that are out in the open, traveling about in your blood and lymph. Humoral immune cells include: B-cells Antibodies Phagocytes Granulocytes Monocytes Dendritic cells B-cells When talking about humoral immunity, B-cells are at the head of the pack. The "B" in B-cells is now generally understood to refer to the "B" in bone marrow, where they are generated. B-cells travel directly from the bone marrow into your bloodstream. They do not pass go; they do not collect $200; and they do not go to the thymus like T-cells for specialized training. In fact, each B-cell comes out of the bone marrow programmed to make one specific antibody to defend against one specific invader. An antibody, by the way, is a soluble protein produced by B-cells that's capable of binding to and destroying or neutralizing one particular foreign substance (antigen) in the body. Antibodies belong to a particular family of nine proteins called the immunoglobulins. Antibodies in our immune system react with specific antigens to kill or neutralize them. They have a specific geometry that is crucial to their function. It is not quite like the lock and key mechanism of the T-cells, but it does include geometry specific antigen binding sites that grab onto and bind to specific antigens, as implied in the illustration above. So, one B-cell, for example, produces one particular antibody to defend against one particular strain of flu, whereas an entirely different B-cell produces the antibody for the strep bacteria, and so on. Note: there is a subset of B-cells that is a bit less specific and can work against multiple antigens. In fact, there are several subsets of B-cells, but four are primary. 1. B2-cells are the specific antigen cells that we primarily think of when referring to B-cells, and will be the primary B-cells we discuss below. 2. B1-cells have an affinity for multiple antigens. They are present in much fewer numbers than B2-cells and are found primarily in the peritoneal and pleural cavities.

3. Plasma cells are the large cells produced by B-cells that have been exposed to a particular antigen. They are short lived -- about one week -- and die off quickly once no longer needed. 4. Memory B-cells are formed from "activated B-cells" -- B-cells that have been exposed to an antigen and finished attacking it. These function much like memory T-cells in that they are specific to the antigen encountered during the primary immune response. Memory B-cells live for a long time and, like memory T-cells, can respond quickly following a second exposure to the same antigen. A critical difference between B-cells and T- cells is how each lymphocyte recognizes the antigen they're geared to seek. As we discussed in Part 1 of our series, since T-cells have to identify invaders "hidden" inside body cells, they don't get to look for the entire antigen. Instead, they have to recognize their targeted invader in a "processed" form, as a peptide fragment (a protein molecule) presented by the MHC molecule on the cell's surface -- the key to the T-cell's lock, as it were. To learn this skill, they are trained in the thymus. B-cells, on the other hand, have an easier task. They get to look for their targeted antigen in its complete and unprocessed native form. They don't have to look for bits and pieces of viral proteins, for example, they get to examine the complete target in all its glory. They get to track down free (soluble) antigens in the blood or lymph using their BCR (Bcell receptor) or membrane bound-immunoglobulin. To give you an analogy; it's like playing "Name that Tune." B-cells get to listen to the entire song before having to identify it; T-cells have to "name that tune" in just three notes.2 Much harder! As mentioned previously, B-cells work primarily in the blood and lymph, defending against "foreign" invaders and toxic molecules. (In general, they are not as good at defending against the body's own cells that have "gone bad" as T-cells, although in some cases, antibodies can indeed attack cancer cells.) By themselves, B-cells cannot produce a sufficient number of antibodies to overwhelm an invader. Instead, once a B-cell encounters the particular invader that it is built to defend against, it produces a vast number of plasma cells to manufacture the antibodies for them. Plasma cells are large cells that are essentially "factories" that produce millions of specific antibodies and release them into the bloodstream. Every single clone of the original plasma cell produced from a specific B-cell secretes a specific antibody for a single antigen. It is extremely specific. Each antibody targets one specific antigen and one only. Once the invader has been eliminated, the B-cells stop production of the plasma cells, and in a short period of time, most of the antibodies fade away. Interestingly, even though they "work" in body fluids, B-cells do not generally circulate in the blood or lymph. Instead they camp out in the lymph nodes, spleen,

and intestinal lymphatic tissue -- waiting to be called into action. Like T-cells, they require costimulation to start working. The first stimulation comes from antigen receptors on their surfaces. They are activated by recognition of a specific antigen. The costimulation comes from interleukins (interleukin 2, 4, and 5) dispensed from T-helper cells. Once an invader has been recognized and the B-cells have been costimulated by a T-helper cell, they differentiate into plasma cells. As I mentioned previously, plasma cells function as antibody factories and secrete antigen-specific antibodies at a rate of millions of millions of molecules per cell per second. This is a major, major immune event/response. Antibodies Antibodies are Y-shaped protein molecules produced by B-cells that function as your body's primary immune defense. Compared to the other components of the immune system, they are tiny. However, since they are proteins, they are also remarkably complex and composed of hundreds of amino acids folded over and over on each other, ultimately forming two chains. Their numbers dwarf by many magnitudes the numbers of T-cell defenders and macrophages. Each antibody molecule and its clones has a unique binding site that is set to combine with the complementary site of a foreign antigen. In the image below, on the left, you can see a representation of the complex folded amino acid structure of the antibody. On the right, there's a representation of how the unique binding sites work.

Unlike T-cells, antibodies do not "actively" defend. They do not penetrate cell walls. They do not "consume" invaders, nor do they inject them with protein toxins. There is no "kiss of death" as seen with T-cells. Like Lilliputians taking on Gulliver, antibodies defeat invaders by sheer force of numbers. Antibodies work by physically attaching themselves to the surface of an invading cell in massive numbers. The medical term for this is agglutination, which is

defined exactly as it sounds (a gluing together). This has several possible effects on invaders such as bacteria. First, as more and more and more and more antibodies "agglutinate" to the bacteria, it becomes heavier and heavier until it literally precipitates out of the body fluid in which it is floating. At that point, it becomes easy prey for roving macrophages looking for detritus to eat up. The medical term for "coating" bacteria and other cells and rendering them subject to phagocytosis (being engulfed by phagocytes) is opsonization.
3D_Medical_Animation_Antibody_Immune_Response_-_YouTube.flv

A secondary effect of massive agglutination is that the antibodies eventually build up to the point where they immobilize ciliated or flagellated bacteria. Once immobilized, they become easy targets for the macrophages. Ciliated bacteria are those that move about by virtue of all the little hairs on their surface, like the oars on a Roman galley. Flagellated bacteria, on the other hand, move about through the rotating motion of a tail-like structure that moves them forward like the propeller on a boat. When covered with antibodies, both processes come to a halt and the bacteria are immobilized. Agglutination also allows antibodies to neutralize toxins from bacteria, such as tetanus, by literally encasing the toxins. Tetanus toxoid immunization injections, incidentally, artificially stimulate antibody production before exposure. (Immunization by vaccination is a controversial topic in the alternative health community, to say the least. We'll talk more about immunization, the pros and cons, later on in our series on the immune system.) And finally, antibodies serve as a form of preventative care in that they can stop viruses before they have a chance to enter cells, do their damage, and replicate exponentially. Note: doctors often make use of antibodies' specificity for particular antigens by cloning them in the laboratory to target specific antigens for either diagnosis, the delivery of chemicals, or even the ability to precisely delivery controlled doses of radiation. Antibodies cloned in the laboratory for these purposes are known as monoclonal antibodies. Phagocytes Most people are not aware of what phagocytes are or exactly what they do; nevertheless, when they think of the immune system, if they think of it at all, phagocytes are probably the cells they are thinking of. Phagocytes are the large white cells that eat and digest invading pathogens, primarily through protease enzyme activity. There are several kinds of phagocytes: Macrophages Neutrophils

Monocytes The word macrophage translates from the original Greek as "big eater." And in fact macrophages are among the larger cells of the immune system and have a number of functions. Not only do they attack foreign invaders, they also play a key role as scavengers by "eating up" worn out cells and other waste in the body -referred to as necrotic tissue -- especially in the lungs. Once macrophages have "digested" an invader, they then present the key identifying molecules, or antigens, to the T-cells to initiate the immune response. From an alternative health point of view, macrophages play a key role in fasting. When you are not eating and creating new waste in the body, macrophages get a chance to "get ahead of the game" in terms of cleaning up debris. Fasting time thus becomes "spring cleaning" time for macrophages. Incidentally, macrophages look like amoebas, flowing from point to point, as they move about in pursuit of "enemies." On another note, macrophages can play a significant role in the destruction of metastases in the early phases of tumor development, at least if your immune system is functioning properly. Unfortunately, at a certain point, tumors usually develop the ability to shut down macrophage attacks, thus ensuring their own survival. As always, it is easier for your immune system to prevent cancer from taking root than to eliminate it once it has. It of course can be done, but it takes much more effort and is more problematic.3 Neutrophils, which are classed as both phagocytes and granulocytes, are actually the most abundant white cell in the body, comprising about 50% to 60% of the total circulating white blood cells, with each liter/quart of blood containing about five billion neutrophils. They have a very short life span, only living about six hours after leaving the bone marrow. However, it only takes them about 30 minutes to reach the site of an infection once they are released. Neutrophils rapidly attack any microorganisms coated with antibodies and kill them by eating them up, poisoning them with granule proteins, or capturing them in ultrafine nets created from their own DNA. Very cool! Once they have finished their work, they die and become the prime constituent of pus, along with captured bacteria, tissue debris, and blood serum. At certain stages of cancer development, at least for some tumors, neutrophils can help fight cancer.4,5 However, once tumors are established, certain types of tumors, such as breast cancer, don't just shut down neutrophils, they can actually co-opt them to promote the growth and invasive nature of that tumor. 6,7 Once again, it easier for the immune system to prevent cancer than to reverse it once it's established. Once cancer is established, you need to be more selective in how you use the immune system to reverse it. Monocytes are sort of the reserve, undifferentiated cells of the immune system. They don't actually do much of anything themselves. Their importance lies in what

they can become. They circulate in the blood for about three days after creation and then go hang out in different areas of the body, with about 50% being stored in the spleen, waiting to be called into action. As required by the nature of the infection or inflammation, they will flock to the area under attack and differentiate into macrophages and dendritic cells -- thus providing a huge influx of warriors as needed. Granulocytes Granulocytes are named after the granular texture of their cytoplasm, which needless to say is granular. They include neutrophils (which function like phagocytes, but have the granular texture of granulocytes), eosinophils, basophils, and mast cells. Granulocytes destroy invaders by releasing granules filled with potent chemicals. Eosinophils play a key role in the killing of parasites through several specialized, highly toxic proteins present in the granules they release, including toxic basic protein and cationic protein. Basophils aren't so much killers in their own right; they act more as facilitators. They release histamine and prostaglandins at the site of infection, which creates increased permeability of the tissue in the area, thus allowing for easier phagocyte migration to the site of infection so that the phagocytes can consume the invading microbes. In a normal, healthy immune system, granulocytes will aggressively kill certain types of cancer cells -- at least until such time as the cancer figures out how to shut down the immune system. See for yourself.
Human_granulocytes_kill_cervical_cancer_cells_-_YouTube.flv

Dendritic Cells Dendritic cells have long threadlike tentacles that are used to wrap up antigens and expended lymphocytes and carry them to the lymph nodes for removal from the body. However, their primary function is to identify antigens, process them, and present them to the T-cells and B-cells to initiate the immune response. Boosting your immune system Now that we've slogged through a number of the details about the immune system, it's time to collect the first piece of our reward -- a discussion of how to actually boost immune function. And since we now have some shared background in the science behind immune function, we can do more than just list magic pills and herbs that you need to take on faith; we can actually discuss why and how they work -- and work they do. Scientists have known for years that it is possible to improve the functioning of your immune system. The conventional medical approach has been to use expensive, proprietary drugs, including concentrated cytokines such as interleukin and interferon. Alternative healers, on the other hand, have adopted a more nuanced approach using natural substances to:

Stimulate and strengthen the immune system Fight infection Strengthen tissue against assault by invading microorganisms Stimulate macrophage capability Increase T-cell production and protect helper T-cells Complement the action of interferon and interleukin-1 Promote increased production of cytokines Assist the cell-mediated immune response With that in mind, let's take a look at some natural immune boosters. Not only are natural immune boosters safer than their pharmaceutical alternatives (having fewer side effects), they are, surprisingly, often more powerful-- at least up to this point in time. Echinacea

There are several different ways that immune boosters can power up your immune system. One of the simplest is by presenting your immune system with what it perceives as a non-specific threat -- a foreign antigen -- that in actuality offers no real threat to the body. This causes your immune system to "power up" its defenses. However, since the immune booster presents no actual threat to the body, the immune system has nothing to use its new found readiness against. And thus it waits, charged up, primed for some/any threat to manifest so that it can jump on it with a vengeance. One thing to keep in mind about this kind of immune booster is that the immune system can be fooled by a false threat for only so long before it says to itself, "Ah, you're just yankin' my chain. I'm onto what's happening here -time to stand down." And thus the supplement stops working. When using immune boosters of this type, it's best to use them for three weeks on and one week off. By taking that one week off, the immune system quickly forgets the false threat

presented to the immune system. Thus, you can pull its leg again and again, while keeping your immune system on high alert indefinitely. You can do this because no memory cells are produced by the immune system since the immune system never actually gets to take the final step of "attacking" the immune booster, which is required for production of memory cells. Note: if someone is highly sensitive to the antigens presented by this type of immune booster, their immune systems can actually "kick over" into an actual allergic response to the immune booster and produce symptoms such as sneezing and watery eyes, for example. For sensitive people, then, this type of immune booster is not useful. It should also be noted that this type of response can be plant part dependent. With Echinacea, for example, more people are sensitive to supplements made with Echinacea flowers as opposed to Echinacea seeds and roots. Fortunately, the strongest bioactives are in the Echinacea seeds and roots, not the flowers. Echinacea (purple coneflower) was "discovered" in the late 1800's by a traveling salesman named Joseph Meyer, who learned about it from the Plains Indians while traveling out West. He brewed it up as an alcohol tincture and sold it as a cure all -demonstrating its effectiveness by drinking his tonic and letting rattlesnakes bite him. Needless to say, he never got sick, from whence comes the phrase "snake oil." How does Echinacea work? In addition to tricking the immune system to ramp up, Echinacea helps in several other ways. First, it contains echinacoside, a natural antibiotic comparable to penicillin in effect, which can kill a broad range of viruses, bacteria, fungi, and protozoa.8 This makes it invaluable in wound healing and in the treatment of infectious diseases. Research has also reported Echinacea's efficacy in treating colds, flu, bronchitis, and tuberculosis. Echinacea also contains echinacein, a biochemical that protects against germ attack by neutralizing the tissue-dissolving enzyme hyaluronidase, produced by many germs. Among the many pharmacological properties reported for Echinacea, the one demonstrated most convincingly is macrophage activation -- by increasing production of interferon gamma.9 In addition, one study showed that Echinacea extracts can boost T-cell production by up to 30 percent more than immune boosting drugs. 10 Echinacea also increases production of the chemokines interleukin-8 and MCP-1, which enhance the migration of immune cells to the site of infection. There are two primary varieties of Echinacea: purpurea and angustifolia. They are similar, but also have complementary properties. Formulas that use both are more likely to be effective. It's also worth noting that potency runs from seed to root to leaf to almost none in the flower. And of course herb quality is paramount. Over the last few years, there have been several studies that claimed to debunk Echinacea's ability to boost the immune system and fight colds. Suffice it to say that the studies were either flawed in design (reviews of previously flawed studies),

used the wrong parts of the Echinacea plant (flowers and leaves rather than roots and seeds), or used it at the wrong strength. A more recent study (2010), however, conducted using good quality Echinacea at a significant dose, found little benefit to using Echinacea in terms of reducing the length of a cold.11 Not surprisingly, the press jumped all over it, proclaiming Echinacea was now proven to be little more than a placebo. However, two aspects of the study's protocol negate the results. 1. Dosing with Echinacea commenced at the onset of symptoms. This is too late to capitalize on Echinacea's primary ability to ramp up the immune system. Once symptoms start, your immune system is going to be responding to the antigens presented by the cold virus so adding Echinacea will provide little added immune benefit at that point. (Remember, the key to Echinacea is ramping up the immune system "before" the invader arrives.) Any benefit will come from its germ killing properties, which although real, are secondary. And in that regard, the Echinacea did shorten the duration of colds -- just not by that much. In truth, the major benefit of Echinacea is in its ability to prevent you from getting a cold in the first place -- not shortening its duration -- if you've been using it to build up your immune system in advance of being exposed to the virus. 2. If you are going to wait until the last second, you have to intervene during the incubation phase at the latest, before symptoms fully manifest. And, at least with Echinacea, you have to use a liquid extract for quicker absorption. Once you hit the incubation phase, it's only a matter of hours before the virus kicks into full gear. Waiting for an Echinacea pill to dissolve and make its way through the digestive tract takes too long. (We'll talk more about the incubation phase when we talk about pathogen destroyers in Part 3 of our series.) Forget the negative studies. Echinacea still stands as a powerful immune booster. Pau d'arco Pau d'arco (Tabebuiaavellanedae, impetiginosa, and heptaphylla) is a tree that comes from the rain forests of Brazil and other areas of South America. It is the inner bark of the tree that provides the medicinal function. Like Echinacea, this amazing herb both stimulates the body's defense system and actively attacks pathogenic organisms. It has been used for centuries to improve immune function, detoxify, and reduce pain throughout the body, especially in the joints. Research has shown that it contains a natural antibacterial agent, has a healing effect on the entire body, cleanses the blood, and kills viruses. Pau d'arco has been used as a treatment for AIDS, allergies, infections and inflammations, anemia, asthma, arthritis and rheumatism, arteriosclerosis, bronchitis, cancer, candidiasis, colitis, cystitis, diabetes, eczema, fistulas, gastritis, gonorrhea, hemorrhages, Hodgkin's disease, liver disease, leukemia, lupus, multiple sclerosis,

osteomyelitis, Parkinson's disease, prostatitis, psoriasis, skin sores, snake bites, ulcers, varicose veins, warts, and wounds. The primary active biochemicals in Pau d'arco are the naphthoquinones: lapachol and beta-lapachone. Researchers have shown that lapacholhas antitumorous, antiedemic, anti-inflammatory, antiseptic, antiviral, bactericidal, and antifungal activity.12 Suma Natives of the Amazon jungle have used suma root (Pfaffiapaniculata) for at least the last 300 years. It wasn't until 1975, however, that Suma was tested at the University of So Paulo, Brazil. The studies concluded that although it was not a cure, suma nevertheless brought significant relief for cancer,13 diabetes, and gout sufferers, with no undesirable side effects. Since then, studies at the American College of the Healing Arts have indicated that consistent use of suma may help combat fatigue (including treatment of chronic fatigue and low-energy conditions), prevent colds and flu, speed healing, regulate blood sugar, and stimulate the sex drive. The key working ingredients in suma are pfaffic acid (prevents the spread of various cell disorders), pfaffocides and other saponins (helps stop diseases already in progress), the plant hormones sitosterol and stigmasterol (prevent cholesterol absorption and improve blood circulation), allantoin (helps accelerate healing), and germanium. Suma has one of the highest concentrations of germanium sesquioxide (Ge-132, aka organic germanium) of any plant known. Discovered about thirty years ago, Ge-132 works much like Pau d'arco in that it stimulates production of interferon gamma, while at the same time activating cytotoxic natural killer cells and macrophages. The net result is that it can invigorate the body, restore sexual function, protect against miscarriages, heal burns, reduce pain, treat circulatory disorders, and shrink cancers, in addition to being a powerful immunostimulant.14 Medicinal Mushrooms Many of the compounds found in reishi, maitake, and cordyceps mushrooms are classified as host defense potentiators: it is believed that combinations of these compounds target and strengthen the human immune system, as well as aid in neuron transmission, metabolism, hormonal balance, and the transport of nutrients and oxygen. Through a host-mediated (T-cell) immune mechanism, they help the body regulate the development of lymphoid stem cells and other important defense responses. Reishi (Ganodermalucidum or lingzhi) -- The anti-cancer15 and immune-enhancing effects16 of the reishi mushroom are thought to be largely due to its mucopolysaccharides, which the body incorporates into cellular membranes, making them resistant to viruses and pathogenic bacteria and the triterpenes, which

induce tumor necrosis factor production. The polysaccharides appear to activate macrophages that "consume" viruses, bacteria, and other large particulate matter.

Maitake (Grifolafrondosa, also known as Sheep's Head and Hen of the Woods) -Maitake mushrooms have a very high concentration of a unique polysaccharide compound called beta-1,6-glucan, which researchers consider to be one of the most powerful immune stimulants and adaptogens known. One study showed that maitake produced a 64 percent inhibition of breast cancer and tumor activity and a 75 percent inhibition of skin cancer and tumor activity.17 Also, laboratory studies conducted at the U.S. National Cancer Institute (NCI) and the Japanese National Institute of Health showed that maitake extract kills the human immunodeficiency virus (HIV) and enhances the activity of helper T-cells.18 In fact, the NCI researchers reported that the maitake extract was as powerful as AZT (a commonly prescribed AIDS drug) but without the toxic side effects. Research has demonstrated that maitake stimulates the production of a variety of immune cells, including macrophages, NK cells, and T-cells, and it increases their effectiveness by increasing the production of interleukin-l, interleukin-2, and lymphokines. It also stimulates the bone marrow to produce stem cells and granulocytes by stimulating production of the cytokine granulocyte colony stimulating factor.19 Further, maitake has been confirmed to have a multifaceted benefit for treating cancer and tumors: it protects healthy cells from becoming cancerous, helps prevent the spread of cancer (metastasis), and slows or stops the growth of tumors.20 Maitake works in conjunction with chemotherapy by lessening the negative side effects (by as much as 90 percent). Cordyceps has properties similar to those of ginseng and has been used to strengthen and rebuild the body after exhaustion or long-term illness. It is one of the most valued medicinal fungi in Chinese medicine. It has also been used

traditionally for impotence, neurasthenia, and backache. Recent research with extracts of Cordyceps has yielded a protein-bound polysaccharide with activity against tumors, as well as being capable of upregulating macrophage activity, 21 and inducing the apoptosis (cell death) of human leukemia cells.22 Cordyceps is widely employed to treat upper respiratory problems, impotence, and weakened immune systems, and also by athletes to increase endurance. AHCC (Active Hexose Correlated Compound) -- AHCC is a proprietary dietary supplement rich in polysaccharides and fiber derived from mushrooms. Studies have shown that it can be effective in stimulating the production of NK cells, killer T-cells, and cytokines (interferon, interleukin-12, and TNF-alpha). In Japan, it is used extensively in hospitals in combination with chemotherapy treatments to reduce the adverse side effects of those treatments.23 Astragalusmembranaceus Astragalus has been a foundational herb in Traditional Chinese Medicine for hundreds of years. It is one of the important "Qi tonifying" adaptogenic herbs from the Chinese materiamedica. Current research on astragalus focuses on the immune stimulating capacity of its polysaccharides and saponins. It also appears to be useful in dealing with cancer24 and in increasing stamina. First and foremost, though, it is an immunostimulant25 used in the treatment of chronic viral infections, hepatitis, edema, common cold, and flu. Astragalus increases the interferon response to viral infection and works synergistically with interferon. It also increases phagocytic activity and antibody levels and improves the functioning of natural killer cells. Aloe vera The polysaccharide component of aloe vera, acemannan, possesses significant immune-enhancing and antiviral activity. Supplementing with acemannan has been proven to increase lymphocyte response to antigens by enhancing the release of interleukin-I. In addition, acemannan has been shown to increase macrophage levels and have a positive effect on T-cell activity and dendritic cell maturation.26 Look for whole leaf aloe extract, which is two to three times more potent than gel/juice. Why? The greatest concentration of active ingredients is at the interface of the rind and the inner gel. If your extract doesn't come from the whole leaf, you lose 200-300% of the active biochemicals.

Alkylglycerols Alkylglycerols (AKGs) are lipids naturally manufactured in the body and found in mother's milk, the liver and spleen, and bone marrow. They play a major role in the production and stimulation of white blood cells. They also help to normalize bone marrow function. The immune-supportive effect of AKGs helps our bodies protect against bacterial, fungal, and viral infections through enhanced phagocytosis (eating up the bad guys) and antibody production.27 The most potent source of AKGs in the world is shark liver oil. Colostrum and Lactoferrin Colostrum is the clear, yellowish, pre-milk fluid produced from the mother's mammary glands during the first seventy-two hours after birth. It provides both immune and growth factors essential for the health and vitality of the newborn. Obviously, supplementation with human colostrum is not an option, but researchers have found that bovine colostrum (from cows) is virtually identical, except that the immune factors are actually several times more concentrated. The immune factors in colostrum have been shown to help the body resist pathogens such as viruses28 bacteria, yeast, and fungi. In addition, colostrum contains a number of antibodies to specific pathogens, including E. coli, salmonella, rotavirus, Candida, streptococcus, staphylococcus, H. pylori, and cryptosporidia. Proline-rich-polypeptide, a component of colostrum, works as an immunomodulator, boosting a low immune system and balancing an overactive one. (We'll talk more about immunomodulators in our next newsletter.) Another key component of colostrum is transfer factors, small molecules that transfer immunity information from one entity to another. In effect, they transfer immunity "memory," thereby giving you instant resistance to a number of diseases. Colostrum is a potent source of lactoferrin, a globular protein produced in the body. It is found anywhere that is especially vulnerable to attack, such as in the

gut, eyes, ears, nose, throat, and urinary tract. Lactoferrin has been shown to inhibit virus replication (including AIDS and herpes viruses), limit tumor growth and metastasis, directly kill both bacteria and yeast (including Candida), and activate neutrophils. Supplementation with lactoferrin can significantly boost the immune system and help the body recover from any existing infection. Maintaining healthy levels of intestinal flora through the use of probiotic supplements allows the body to produce its own lactoferrin. Look for colostrum obtained from organic, grass-fed dairy cows and standardized to 40% Immunoglobulins. Glutathione Glutathione is a tripeptide molecule found in human cells. In addition to being a powerful antioxidant, glutathione works to support the active functioning of the immune system and is a key component of all lymphocytes. In fact, all lymphocytes require sufficient levels of intracellular glutathione to function properly. It also plays a major protective role against the damaging effects of the whole range of pathogens and carcinogens. For many people, glutathione supplements are upsetting to the stomach. Alternatives include the glutathione precursors L-cysteine and L-glutamate and specially formulated whey products. Mangosteen Mangosteen (Garciniamangostana) is a tropical evergreen tree whose contains a unique group of antioxidants called xanthones. Xanthones, particularly beta and gamma mangostin, work to maintain the immune system, support cardiovascular health, optimize joint flexibility, are naturally antibiotic, antiviral, and antiinflammatory, and are some of the most powerful antioxidants found in nature. In addition, recent studies have confirmed that gamma mangostin is a potent COX inhibitor, an important factor in reducing inflammation, pain, and fever. Other studies have shown that alpha-mangostin can enhance the body's innate responses to viral infection.29 And as has been true with most of the other immune boosters we've looked at so far, mangosteen has also shown the ability to work as an anticancer agent. Specifically, the antimetastatic activity of alpha-mangostin has been demonstrated in clinical studies on breast cancer.30 Beta-glucan Beta-glucan is a natural complex carbohydrate (polysaccharide) found in cereal grains such as oats and barley. However, it is found in its greatest concentration primarily in the cell walls of yeast and in medicinal mushrooms. Beta-glucan as a supplement, however, particularly Beta- 1,3/1,6 glucan, extracted from yeast cell wall, is a potent and proven immune response potentiator and modulator -stimulating anti-tumor and antimicrobial activity by binding to receptors on macrophages and other white blood cells and activating them.31

Conclusion In this part of our series on the immune system we covered the humoral immune system (B-cells and antibodies), and explored some of the ways you can enhance your immune system. In addition, we learned that natural immune enhancement can follow several different routes, from tricking the immune system into thinking it's under attack to increasing cytokine production to stimulating the production of immune cells to providing specific building blocks (such as glutathione) that your immune system needs to function. One other important thing that we learned about is the connection between the immune system and cancer and how most immune boosters also function as anticancer agents, each helping your body fight cancer and metastasis in their own unique way. Also, by combining what we've learned over the first two parts of this series, we've gained an understanding of how the immune system actually does this. In simple terms, as genes in a human cell are damaged or mutate over time, eventually turning the cell cancerous, they signal that change in their internal structure by expressing different protein molecules on the cell's surface. At a certain point, these changing surface proteins tell the immune system that the cancer cell is no longer "self", but "non-self" and must be attacked. Obviously, this is not a flawless process, or no one would ever come down with cancer. But it is a process that can be encouraged, supported, and enhanced -- both through natural and medical means -- and in fact, a potentially revolutionary breakthrough in the treatment of cancer that was just announed does exactly that. 32 In a future newsletter series, when I revisit cancer, we'll cover this subject in more detail. In the next part of our series, we'll explore: The complementary immune system Circulating immune complexes Natural immunomodulators Potential problems with the immune system Pathogen destroyers and the incubation phase How we build immunity

1. Alfred, Lord Tennyson. "The Charge of the Light Brigade." eserver.org. Accessed 24 August 2011 2. Name that Tune. <http://www.youtube.com/watch?v=dWPvZI-ZnfQ> 3. Whitworth PW, Pak CC, Esgro J, Kleinerman ES, Fidler IJ. "Macrophages and cancer." Cancer Metastasis Rev. 1990 Feb;8(4):319-51. <http://www.ncbi.nlm.nih.gov/pubmed/2182211> 4.Fady C, Reisser D, Martin F. "Non-activated rat neutrophils kill syngeneic colon tumor cells by the release of a low molecular weight factor." Immunobiology.1990.Aug;181(1):1-12. <http://www.ncbi.nlm.nih.gov/pubmed/2272641> 5. Blanks MJ, Stehle JR Jr, Du W, Adams JM, Willingham MC, Allen GO, Hu JJ, Lovato J, Molnar I, Cui Z. "Novel Innate Cancer Killing Activity in Humans." Cancer Cell Int. 2011 Aug 3;11(1):26. [Epub ahead of print] <http://www.ncbi.nlm.nih.gov/pubmed/21813015> 6. Marisa M. Queen, Randall E. Ryan, Ryan G. Holzer, Cynthia R. KellerPeck, and Cheryl L. Jorcyk. "Breast Cancer Cells Stimulate Neutrophils to Produce Oncostatin M: Potential Implications for Tumor Progression." CancerRes October 1, 200565;8896 <http://cancerres.aacrjournals.org/content/65/19/8896.full>

7. Alyssa D. Gregory1 and A. McGarry Houghton. "Tumor-Associated Neutrophils: New Targets for Cancer Therapy." Cancer Res April 1, 2011 71; 2411. <http://cancerres.aacrjournals.org/content/71/7/2411> 8. Stoll, A., A. Renz& A. Brack. Antibacterial substances II. Isolation and constitution of echinacoside, a glycoside from the roots of echinaceaaugustifolia. Helvetic ChimicaActa, 33, 1877-1893, 1950. 9. Barrett B., Medicinal properties of Echinacea: A critical review, Phytomedecine, 2003, vol. 10, no1, pp. 66-86 [21 page(s). <http://www.ncbi.nlm.nih.gov/pubmed?term=12622467 > 10. Wagner H, Proksch A. An immunostimulating active constituent from Echinacea purpurea. Z Phytother 1981;2:166-171. 11. Bruce Barrett, MD, PhD; Roger Brown, PhD; Dave Rakel, MD; Marlon Mundt, PhD; et al. "Echinacea for Treating the Common Cold - A Randomized Trial." Annals of Internal Medicine. December 21, 2010 vol. 153 no. 12 769-777. <http://www.annals.org/content/153/12/769.abstract> 12.Tandon VK, Singh RV, Yadav DB. Synthesis and evaluation of novel 1,4-naphthoquinone derivatives as antiviral, antifungal and anticancer agents. Bioorg Med ChemLett. 2004 Jun 7;14(11):2901-4. <http://www.ncbi.nlm.nih.gov/pubmed/15125956> 13. T Watanabe, M Watanabe, Y Watanabe, C Hotta. "Effects of oral administration of Pfaffiapaniculata (Brazilian ginseng) on incidence of spontaneous leukemia in AKR/J mice." Cancer Detect Prev. 2000;24(2):173-8. <http://www.ncbi.nlm.nih.gov/pubmed/10917139> 14. Stephen A. Levine, Ph.D. "Organic Germanium A Novel Dramatic Immunostimulant." Orthomolecular.org, (Accessed 27 Aug 2011) <http://orthomolecular.org/library/jom/1987/pdf/1987-v02n02-p083.pdf> 15.Xu Z, Chen X, Zhong Z, Chen L, Wang Y. "Ganodermalucidum polysaccharides: immunomodulation and potential anti-tumor activities." Am J Chin Med. 2011;39(1):15-27. <http://www.ncbi.nlm.nih.gov/pubmed/21213395> 16. Watanabe K, Shuto T, Sato M, Onuki K, Mizunoe S, Suzuki S, Sato T, Koga T, Suico MA, Kai H, Ikeda T. "Lucidenic acids-rich extract from antlered form of Ganodermalucidum enhances TNFa induction in THP-1 monocytic cells possibly via its modulation of MAP kinases p38 and JNK." BiochemBiophys Res Commun. 2011 Apr 29;408(1):18-24. Epub 2011 Mar 29. <http://www.ncbi.nlm.nih.gov/pubmed/21453678> 17. Hiroaki Nanba, Ph.D. "Maitake D-fraction: Healing and Preventive Potential for Cancer." The Journal of Orthomolecular Medicine Vol. 12, 1st Quarter 1997. <http://orthomolecular.org/library/jom/1997/articles/1997v12n01-

p043.shtml><http://orthomolecular.org/library/jom/1997/articles/1997v12n01-p043.shtml> 18. Ishikawa, K. "Anti-HIV Activity in Cytopathic Effect of Proteoglucan Extracted from Maitake Mushroom," National Institute of Health, Jan 23, 1991. 19. Ito K, Masuda Y, Yamasaki Y, Yokota Y, Nanba H. "Maitake betaglucan enhances granulopoiesis and mobilization of granulocytes by increasing G-CSF production and modulating CXCR4/SDF-1 expression." IntImmunopharmacol. 2009 Sep;9(10):1189-96. Epub 2009 Jun 30. <http://www.ncbi.nlm.nih.gov/pubmed/19573626> 20. Kodama N, Mizuno S, Nanba H, Saito N. "Potential antitumor activity of a low-molecular-weight protein fraction from Grifolafrondosa through enhancement of cytokine production." J Med Food. 2010 Feb;13(1):20-30. <http://www.ncbi.nlm.nih.gov/pubmed/20136432> 21. Lee JS, Hong EK. "Immunostimulating activity of the polysaccharides isolated from Cordycepsmilitaris." IntImmunopharmacol. 2011 Sep;11(9):1226-33. Epub 2011 Apr 14. <http://www.ncbi.nlm.nih.gov/pubmed/21497206> 22.Jeong JW, Jin CY, Park C, Hong SH, Kim GY, Jeong YK, Lee JD, Yoo YH, Choi YH. "Induction of apoptosis by cordycepin via reactive oxygen species generation in human leukemia cells." ToxicolIn Vitro. 2011 Jun;25(4):817-24. Epub 2011 Feb 15. <http://www.ncbi.nlm.nih.gov/pubmed/21310227> 23.AHCC Published Research. Accessed 28 Aug 2011. <http://www.ahccpublishedresearch.com/default.htm> 24.Auyeung KK, Mok NL, Wong CM, Cho CH, Ko JK. "Astragalussaponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells." Int J Mol Med. 2010 Sep;26(3):341-9. <http://www.ncbi.nlm.nih.gov/pubmed/20664949> 25. Liu QY, Yao YM. "The regulatory effect and mechanism of Astragalus polysaccharides on CD11c(high)CD45RB(low) dendritic cell." Zhonghua Shao Shang ZaZhi. 2011 Apr;27(2):95-9. <http://www.ncbi.nlm.nih.gov/pubmed/21651844> 26. Lee JK, Lee MK, Yun YP, Kim Y, Kim JS, Kim YS, Kim K, Han SS, Lee CK. "Acemannan purified from Aloe vera induces phenotypic and functional maturation of immature dendritic cells." IntImmunopharmacol. 2001 Jul;1(7):1275-84. <http://www.ncbi.nlm.nih.gov/pubmed?term=11460308>

27.Ngwenya BZ, Foster DM. " Enhancement of antibody production by lysophosphatidylcholine and alkylglycerol." ProcSocExpBiol Med. 1991 Jan;196(1):69-75. <http://www.ncbi.nlm.nih.gov/pubmed/1984244> 28. "Clinical Tests: Preventing Colds with APS45-10 Colostrum." Paper presented at Annual Meeting of Japanese Society of Clinical Nutrition 2007, The 13th Symposium of Adult Disease Countermeasure Society 2008, The 14th Symposium of Adult Disease Countermeasure Society 2009 and Annual Meeting of Japanese Dairy Science Association 2009. <http://www.apsbiogroup.com/colostrum/references/Preventing_Colds.pdf> 29.Shaneyfelt ME, Burke AD, Graff JW, Jutila MA, Hardy ME. "Natural products that reduce rotavirus infectivity identified by a cell-based moderate-throughput screening assay." Virol J. 2006 Sep 1;3:68. <http://www.ncbi.nlm.nih.gov/pubmed/16948846> 30. Shibata MA, Iinuma M, Morimoto J, Kurose H, Akamatsu K, Okuno Y, Akao Y, Otsuki Y. "a-Mangostin extracted from the pericarp of the mangosteen (Garciniamangostana Linn) reduces tumor growth and lymph node metastasis in an immunocompetentxenograft model of metastatic mammary cancer carrying a p53 mutation." BMC Med. 2011 Jun 3;9:69. <http://www.ncbi.nlm.nih.gov/pubmed/21639868> 31.Beta Glucan Reasearch. <http://www.betaglucan.org/> 32. David L. Porter, M.D., Bruce L. Levine, Ph.D., Michael Kalos, Ph.D., Adam Bagg, M.D., and Carl H. June, M.D. "Chimeric Antigen Receptor Modified T Cells in Chronic Lymphoid Leukemia." N Engl J Med 2011; 365:725-733 August 25, 2011. <http://www.nejm.org/doi/full/10.1056/NEJMoa1103849>