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Nutrition and Immunity

INTRODUCTION

The immune system is the body’s primary defensive survival mechanism. It can determine what is “self,” which needs to be protected – and what is “non-self,” which needs to be destroyed. A properly functioning immune system allows us to live a life virtually free of illness and disease.

Nutrition plays a key role in maintaining optimal immune function. Recent research has shown that many, if not all, of the body’s defenses can be hindered by malnutrition. Cell-mediated immunity, antibody production, inflammatory response, and secretory and mucosal immunity are some of these functions. Nutritional excesses can also alter the immune response.

This course will address the interrelationships of nutrition, immunity and stress, as diagrammed below.

Interrelationships

Stress can have profound effects on immune function. During stress, the body undergoes physiological, hormonal, neural and physical changes which alter metabolic processes. The immune system is susceptible to the changes brought on by stress; the result can be immunosuppression. Dietary insufficiencies (from poor eating habits during stress) compound the physiological effects of stress by forcing the immune system to function without proper nutrients. Because it may suppress immune function, we should try to minimize the effects of stress on the body.

An aging immune system undergoes changes. This course will define those changes and offer strategies to combat age-related decline in immune function.

Antioxidants and phytochemicals are now in the forefront of research, and often touted in the media as substances that can mitigate the effects of aging and prevent everything to cancer to heart disease. In this latest edition, a chapter on antioxidants and phytochemicals has been added. It will explore the science behind the headlines and explain the rationale for increasing intake of fruits, vegetables, grains and legumes.

An exciting area of research, psychoneuroimmunology (PNI), is providing valuable information about how the brain affects the cells of the immune system and the course of disease. Once the immune system was thought to function on its own, without direction from the brain, but immunologists and other researchers have demonstrated that emotions, beliefs and attitudes control immune function through the production of hormones, neuropeptides and other chemical messengers.

The significance of this research is enormous and helps provide a biochemical explanation for “miraculous” occurrences, such as recovery from terminal conditions. It also helps us understand why some people heal faster than others, or don’t get sick while others do.

In the nearly 10 years since I wrote the first edition of this course, many dietitians and other practitioners have given me valuable advice and feedback on its content. It is impossible to thank them all here, but – as in all such enterprises – I walk in the footsteps of those who have gone before, and would like to acknowledge my appreciation and gratitude for their assistance.

CHAPTER ONE: COMPONENTS OF THE IMMUNE SYSTEM

Without an immune system, life would cease to exist. The immune system has the amazing ability to protect the body from millions of potentially deadly organisms and particles, with survival as the ultimate goal.

To combat continual threats to the body successfully, the immune system has numerous tools at its disposal. The complexity of the immune system seems overwhelming and mysterious. You can point to the chest cavity and immediately understand where the heart is located and how it works. The same can be said of the kidneys, the gastrointestinal tract and most of the other systems of the body. But where, exactly, is the immune system? The answer is “everywhere.”

Many external and internal organs, tissues and cells are intricately involved in protecting the body from deadly threats. Not only is the immune system distributed throughout the body, it also interacts with other systems not necessarily classified as part of the immune system. This further complicates our study.

The immune system is complex, but that does not mean it is impossible to understand. Taking the immune system apart and looking at the individual components makes it easier to understand how all the parts function together.

When discussing the immune system, the most commonly used analogy is a battle: an alien force (viral, bacterial, or parasitic) tries to invade the body, the immune system mobilizes and fights it off, and the body survives. While a battle analogy is somewhat appropriate, it minimizes the subtlety of the highly coordinated, almost elegant performance. This is not a street fight.; the synergy and harmony of the various parts of the immune system are more like a performance by a symphony orchestra, with strings, woodwinds, brass and percussion instruments playing separate but harmonious parts. Each immune system component has its own part to play in the overall survival scheme, but the whole is more than the sum of the various parts.

FUNCTIONS OF THE IMMUNE SYSTEM

The immune system is not “on” or “off.” Parts of the system are functioning all the time, although the intensity may be very low when no active disease or injury is present. When an injury or disease occurs, the immune system gets into high gear to meet the challenge.

The purpose of the immune system is to protect and defend the body against foreign invaders. To do this the body must have the ability to distinguish “self” from “nonself,” and thus know what to attack and what to leave alone. Key functions of the immune system are shown in the chart below.

Functions of the Immune System

  • Distinguish “self” from “nonself”
  • Distinguish between threatening & non-threatening invaders
  • Protect against invaders
  • Adapt to different invaders & threats
  • Protect against its own destructive powers
  • Assure survival of the organism

After the immune system has determined that nonself objects (which we will call antigens or pathogens) have entered the body, and has attacked them successfully, it must also know when to stop. Suppression of the immune response is absolutely necessary to protect the body from undue harm, because during the course of the response both invaders and some cells and tissues of the host are destroyed.

To accomplish these tasks, the immune system must be able to prepare for antigens it has never encountered before and adapt an immune response that destroys them (but does not harm the host). The immune system “learns” how to fight effectively and “remembers” what it has learned.

Appendices #1 and #2 list organs and cells of the immune system, giving their locations and functions. In the rest of this chapter we’ll look at individual components to see how they interact and perform.

NONSPECIFIC RESISTANCE

The body has numerous defenses which are in action all the time to prevent organisms from entering the body or to destroy those that do. These mechanisms do not have to be alerted to combat an invader, and they have limited ability to distinguish one invader from another. Although they are present and active all the time, they may increase their activity in response to a foreign organism. We call the actions of these mechanisms nonspecific resistance (also known as innate, natural, native or non-adaptive immunity). The chart below lists the components and actions of this nonspecific immune system.

Nonspecific Resistance

Although we seldom think of the skin, tear glands, kidneys, GI tract and mucous membranes as part of immunity, they are the body’s first line of defense against nonself. They react to any irritating invader – everything outside the body is nonself; everything inside is self.

The skin, for example, presents a physical barrier that prevents nonself organisms from entering the body. Thus, the skin itself is an immune organ. However, openings may be created by injury, and, once the barrier is broken, foreign substances can gain entrance. The inflammation response combats these unwanted intruders.

In the inflammation response, the barrier has been broken and potentially harmful organisms have entered. Certain cells in the blood and lymph have the ability to phagocytize – surround and engulf – invading microbes. These cells migrate to the site of bacterial, fungal and protozoal invasions and eliminate particles and organisms that have somehow gained entry into the body.

(The inflammation response can also be destructive if it persists over a period of time. In destroying foreign particles, phagocytic cells release substances that can damage the surrounding tissues. The characteristic redness and heat of an inflammation reflect the irritating effects of these chemicals. Continual inflammation, such as is seen in arthritis, can permanently damage the tissue where the inflammation is found – in the case of arthritis, the joints).

Anywhere the barrier between inside and outside is breached is a possible danger zone. There are points of access that are particularly vulnerable, and thus particularly well protected. The two most common entry points for organisms are the respiratory and gastrointestinal systems.

Hairlike projections, called cilia, line the respiratory tract. They trap and hold bacteria-laden particles, while mucosal secretions from the linings of the nose, throat and bronchi (containing lysozyme, a potent bactericidal enzyme) attack and destroy the cell walls of bacteria, killing them.

The gastrointestinal tract has sophisticated mechanisms to protect the body from organisms in the food we eat. Peristalsis – the wavelike action of the smooth muscles of the GI tract – helps prevent organisms from having enough time to pass from the GI tract into the body. As in the respiratory tract, mucosal secretions trap and destroy bacteria. Hydrochloric acid and digestive enzymes can also kill unwanted organisms. Thus, the GI tract presents a physical barrier to prevent antigens from entering body tissues, where they can cause damage, and a chemical action to kill antigens. This is a very active system – naturally, since we ingest so much potentially dangerous organic material.

The genitourinary system (kidneys, bladder) uses mucosal secretions, lysozymes and acidic urine to protect the body from dangerous organisms.

Tears wash the eyes with each blink (or flood the eyes to flush out an irritant) and prevent harmful organisms from penetrating the physical barriers of the eyes. The linings of the eye sockets use mucosal secretions and lysozymes; so do mammary glands.

Nonspecific mechanisms cannot adapt to new types of organisms, so they are therefore limited in their protective ability. To supplement the nonspecific response, the body has a specific response system that involves numerous organs and cells.

ORGANS OF THE IMMUNE SYSTEM

The organs of the immune system (also known as lymphoid tissue) are subclassified as primary and secondary organs. Although many of the cells that are a part of the immune system can be found throughout the body, the organs of the immune system contain the majority of the cells. The following sections introduce the major organ systems and cells, as summarized in the chart below.

Organs of the Immune System

The primary organs are the thymus and bone marrow; secondary organs are the lymph vessels and lymph nodes, spleen, GI tract (Peyer’s patches, GALT), tonsils, adenoids and appendix.

The thymus is the “master gland” of the immune system, most responsible for maintaining immune function. Located under the breastbone, it is largest in infancy and childhood – growing from perhaps 0.5 oz (15 gm) in weight to as much as 1.5 oz (45 gm) at puberty – and begins to shrink after puberty. The thymus has two lobes, each divided into several lobules. Each lobule contains a cortex (outer layer) and medulla (inner layer).

The thymus works with the bone marrow to produce specialized immune cells. While its workings remain a mystery, it seems clear that the thymus acts to “program” some cells to perform specific immune functions.

White blood cells and leukocytes are generic terms used to refer to all the cells of the immune system. These are nucleated white or colorless cells in the blood. The term lymphocyte refers to cells produced by lymphoid tissue; 20 to 30 percent of the leukocytes are lymphocytes.

(We will discuss these cells, and the subcategories within them, in more detail in a later section. The terms have been introduced here to enable you to understand how the organs of the immune system function).

Undifferentiated white blood cells (called precursor stem cells), are produced in bone marrow, the soft material in the hollow of the long bones of the arms and legs. These stem cells are either lymphoid precursor cells or myeloid precursor cells. Lymphoid precursor cells that mature in the bone marrow become B cells (for bone-marrow derived lymphocytes), while those that mature in the thymus gland are T cells (for thymus-derived lymphocytes). Myeloid precursor cells also differentiate in the bone marrow; they may become monocytes, macrophages, or granulocytes (of which the types are neutrophils, basophils or eosinophils), or platelets. (A later section of this chapter will define these kinds of cells and discuss their functions in greater detail).

The lymphoid precursor cells which are destined to become T cells migrate from the marrow to the thymus gland, where they penetrate from the cortex to the medulla.

The thymus produces hormones – thymopoietin, thymosin-alpha-1, thymulin, and thymosin-beta-4 – which transform lymphoid precursor cells into differentiated, mature T cells. In this differentiation and maturation, the cells acquire different surface markers and functions. After maturing, they are released from the medulla into the blood and lymphatic systems and migrate to the peripheral tissues.

The chart below diagrams the development of these various cells.

Cell Differentiation Since the bone marrow is the source of all immune cells, it is essential for the optimal functioning of the immune system. As cells die(naturally or from fighting an invading organism), the bone marrow resupplies them. Any disease that alters bone marrow function will thus interfere with the immune response.

The secondary lymph organs (lymph nodes and lymph vessels) house T and B cells. Since they are spread throughout the body, they can perform their functions close to the site where they are needed, thereby providing a rapid localized response to an invading antigen.

Lymph nodes and vessels are a sort of “garbage disposal” system of the body. The fluid in the lymph vessels transports white blood cells to where they are needed. The lymph nodes contain T and B cells and other white blood cells, particularly macrophages, that engulf and destroy antigens. Lymph nodes are located at the intersection of major lymph vessels.

When the body fights an invading antigen, the lymph nodes immediately become activated. There is an increase in the turnover of lymphocytes, and plasma cells actively secrete antibodies. As the lymph fluid flows through the lymph nodes, cells filter it to remove and destroy antigens. The lymph fluid picks up antibodies and lymphocytes from the nodes, then carries dead cells and debris from the “battlefield.”

Because of their function in storing white blood cells and filtering debris, lymph nodes swell when they are being utilized by the immune system. “Swollen glands” in the throat, groin or armpit are a sign that the body has mobilized an immune reaction to an invading antigen.

To get rid of the debris, the lymph fluid circulates in the lymph vessels to a major lymph vessel, the thoracic duct, which empties into the left subclavian vein. Thus, lymphocytes recirculate into the bloodstream, and waste products are carried to the liver or kidneys to be degraded and eliminated from the body. While in the bloodstream, lymphocytes are transported to the lungs, spleen and other organs and tissues of the body. Lymph nodes, therefore, are a central organ in the circulation of lymphocytes to the rest of the organs in the body. A representation of the entire lymphatic system is shown on the next page, with the nodes represented by the dark areas.

The tonsils and adenoids are specialized lymph glands located where they can react to antigens present in food or air. Removal of these organs is not routine any more, since their role in the immune response is now recognized. The discomfort of tonsillitis can now be mitigated by antibiotic regimes, making removal less necessary.

The spleen, located at the upper left side of the abdomen, plays an important role in immune function, acting as a filter for the lymphatic system and an interface between the lymphatic and blood circulations. Here, tiny blood vessels are surrounded by lymphatic tissues, so that abnormal proteins in the bloodstream can stimulate the production of antibodies.

The spleen also is involved in the conversion of hemoglobin to bilirubin, and houses T and B cells.

Unlike the lymph nodes, the spleen has no lymphatic drainage, so white blood cells are recirculated from the spleen via the bloodstream. The spleen is a fairly large organ, about 5 inches long and weighing about 8 to 10 oz in an adult. Morover, it can swell with infection – an enlarged spleen, like swollen lymph nodes, is indicative of an activated immune system caused by a major infection in the body. While the spleen and lymph nodes have similar functions, the spleen is the site that responds to blood-borne infections, while the lymph nodes respond to infections in the lymph system.

The diagram on the next page shows how lymphocytes circulate between the lymphatic system, bloodstream and most of the organs in the body.

Peyer’s patches and intestinal nodules are instrumental in protecting the body from organisms that enter the GI tract and try to cross the barrier into the bloodstream.

In addition to the nonspecific resistance factors discussed previously, the GI tract has another line of defense – antibodies. These protein molecules bind to antigens so they can be destroyed by phagocytes. Antibodies, macrophages and some T cells are produced in the Peyer’s patches and intestinal nodules. B cells are known to mature there as well.

Peyer’s patches are also known as gut-associated lymphoid tissue (GALT). A similar kind of tissue called bronchus-associated lymphoid tissue (BALT) is found in the lungs.

Circulation of Lymphocytes

SPECIFIC (ADAPTIVE) IMMUNITY

We call specific immunity “adaptive.” T and B cells acquire a chemical memory for a specific type of antigen, enabling them to recognize it and activate themselves and other immune cells. Activated cells are called immunocompetent. There are two types of specific immunity: cell-mediated immunity and humoral immunity.

The chart below shows the components arranged in immune system categories. Unlike nonspecific immunity, adaptive or specific immunity must be triggered by an antigen-presenting cell. Once triggered, all parts begin to work together.

Components of the Immune System

Cell-mediated immunity involves specific cells of the immune system: T lymphocytes (which may be further subcategorized as T helper cells, T suppressor cells or T cytotoxic cells), macrophages, granulocytes and natural killer cells.

Humoral immunity refers to the actions of protein molecules called antibodies (or immunoglobulins), which are produced in the blood by B cells, as well as in the GALT and BALT as mentioned above.

CELLS OF THE IMMUNE SYSTEM

Cells are produced by the immune system in response to an invading organism. The bewildering variety of immune cells attests to the complexity of the system, and the variety of attacking organisms. Generally, immune cells can be broken down into lymphocytes and phagocytes. A complete list of immune system cells and the functions they perform can be found in Appendix #2. This section will define these various cells and their activities.

Phagocytes are scavenging cells that ingest and destroy (phagocytize) antigens. Cells in the phagocyte category include: monocytes, macrophages, neutrophils, basophils, eosinophils and mast cells, which are discussed below.

Granulocytes are immune cells that contain pockets of irritating or lethal enzymes, such as histamine, lysozyme, lysozymal hydrolases, peroxidase and lactoferrin. These are involved in the destruction of antigens and foreign matter. These enzymes can hurt or destroy tissue of the host in the process of killing antigens. Granulocytes can phagocytize antigens and cellular debris. Granulocytes are subcategorized based on their function.

Neutrophils are granulocytes with a powerful bactericidal enzyme. These cells are also known as polymorphonuclear leukocytes or polymorphs (PMN). Eosinophils are granulocytes that may also be involved in regulating the inflammatory response. Basophils are granulocytes that contain heparin and vasoactive amines. During the inflammatory response, basophils dilate the blood vessel so that the blood supply can increase to bring more white blood cells to the tissues. Mast cells are tissue granulocytes, similar to basophils, that contain histamine and are involved in the allergic reaction.

Monocytes/macrophages are the largest nucleated cells of the blood, and can phagocytize antigens. Monocytes develop into macrophages when they enter tissues. The most important role of these cells is their ability to recognize an antigen, bind to it and present it to a T cell. Then the T cell can begin to proliferate in an adaptive immune response against that specific antigen. Macrophages also produce substances – cytokines or monokines – that recruit other inflammatory cells (such as neutrophils) and that produce growth factors for cells to repair injured tissue. In essence, the macrophage is the cell that links nonspecific and specific immunity.

Natural killer cells (NK cells) are lymphocytes derived from the bone marrow, involved in nonspecific immunity. NK cells contain chemical granules which are used to kill certain tumor cells and virus-infected self cells. These cells circulate all the time searching for initiated (cancerous) and mutated cells and virus-infected self cells to kill. Unlike other lymphocytes, NK cells can not recognize specific antigens, therefore are part of nonspecific immunity.

Lymphocytes are a set of cells involved in the specific immune response. These cells have the ability to recognize specific antigens, based on the markers on the outside of the cell. There are various subsets of lymphocytes, each with their own function in the specific immune response.

Lymphocytes that mature in the thymus gland – T cells – are involved in cell-mediated immunity. The T cells are further subdivided into three types of cells, based on their function: T helper cells stimulate T and B cells to respond to antigens, “turning on” the immune response and activating macrophages; T suppressor cells are responsible for inhibiting or “turning off” the immune response when an antigen is no longer present; cytotoxic T cells can kill infected self cells and tumor cells, and activate macrophages.

Lymphocytes that mature in the bone marrow – B cells – produce antibodies that attack a specific antigen. Thus, they are part of humoral immunity. Once stimulated by an antigen, B cells turn into plasma cells, which are mass producers of antibodies. Memory cells are B cells that “remember” a specific antigen, so the next time it is seen in the body, a faster immune response is possible.

Antibodies, also known as immunoglobulins (Ig), are not cells, but protein substances produced by B cells: they are part of specific (adaptive) humoral immunity. The classes of immunoglobulins are: IgA, IgD, IgE, IgG, and IgM.

The primary function of antibodies is to attach to and inactivate antigens. Each antibody is specific to one antigen; a new antigen in the body must have a new antibody produced to combat it. Antibodies also have secondary biologic activities that include the ability to activate complement and to cross the placental barrier. (See the following page for an explanation of complement.)

The chart on the next page summarizes the branches of the immune system and the cells that are a part of each branch.

Cells/Proteins of the Immune System

COMPLEMENT

Complement is the generic term for a series of 25 or more serum proteins which are activated sequentially by the activities of immunoglobulins. Production of complement begins when IgM and IgG bind to the surface of an antigen, or may be stimulated directly by certain bacteria.

Complement is known as an “attachment promoter.” That is, it deposits a substance on cell membranes that helps antibodies and phagocytes bind to antigens, thus enhancing their ability to kill antigens. This is known as opsonization. Other functions of complement are to damage the membranes of antigens, causing lysis of the cell and cell death, and to release peptides (small protein molecules) that cause inflammation.

Without complement, the ability of antibodies to kill foreign antigens is decreased, as it is the complement that is able to lyse cell membranes.

CYTOKINES

The immune response is controlled by a variety of polypeptide molecules, known as cytokines, that act as mediators. These are chemical messengers, directing the action, telling the target cells when to multiply, where to go, what to do, what receptors to produce and when to stop their attack when no longer needed. These substances are the “conductors” of the immune system. All cells of the immune system produce cytokines.

Cytokines are transient, with a very short half-life; they are produced when the immune system is stimulated. Those produced by lymphocytes are known as lymphokines; those produced by macrophages are known as monokines. Generally, monokines and lymphokines are referred to as cytokines, as they will be in this course.

Appendix #3 contains a list of the most important cytokines and their functions in regulating immunity. Cytokines can be categorized based on the part of the immune system they influence, i.e. nonspecific immunity, inflammation, specific immunity, mediators of leukocyte growth and differentiation and stimulators of hematopoesis. The chart below lists the properties and functions of cytokines.

Properties & Functions of Cytokines

  • Produced during activated immune response
  • Activate and inhibit the immune response
  • Produced by all immune cells
  • Act on immune cells and other cells of the body
  • Influence growth & differentiation of immune cells
  • Activate and regulate inflammatory cells
  • Responsible for signals between cells of the immune and inflammatory system
  • Stimulate growth and differentiation of cells in the bone marrow
  • Act as mediators for cells involved in tissue repair

Interleukins (IL) are an important class of cytokines. Seventeen different interleukins have been identified and are referred to as IL-1, IL-2, IL-3, etc. Each is produced by certain cells and has a specific function working alone or synergistically with other cytokines. See Appendix #3 for specifics on each interleukin.

Tumor necrosis factor (formerly known as cachectin) functions as a part of the inflammation reaction and performs multiple immunologic activities. TNF is a chemotactic factor for neutrophils and monocytes – that is, it attracts cells and antigens. It also stimulates neutrophils to destroy antigens, and stimulates the production of prostaglandins, IL-1 and IL-6, which enhance the immune response.

A very potent chemical, TNF may be responsible for the tissue wasting associated with chronic disease. While a certain amount of TNF is necessary for proper immune function, too much may cause serious damage, such as localized hemorrhages, coagulation and tissue necrosis. Small amounts of TNF mediate the localized inflammation reaction. Moderate amounts begin to work on other organs and tissues, such as the liver and bone marrow, to cause fever, production of acute phase proteins and stimulation of the bone marrow to produce leukocytes. High quantities of TNF induce septic shock.

During an acute illness, moderate amounts of TNF and IL-1 help the body fight off antigens. However, chronic production of these cytokines is implicated in the cachexia of chronic illness. When someone has a disease that constantly stimulates the immune system – cancer, AIDS, CHF, autoimmune diseases – TNF and IL-1 is produced in sufficient quantities to induce long-term anorexia, responsible for malnutrition in these groups of people. The chart below shows the effect of TNF on various organs.

Effects of Tumor Necrosis Factor (TNF)

Interferon (INF), a cytokine produced by leukocytes, is important in protecting the body from viral infections. Interferon can enhance or inhibit cell differentiation and is an immunoregulatory agent. More than one type of interferon has been identified: Type I interferon is subdivided into INF alpha and INF beta; Type II INF is noted as INF gamma.

Of the foreign invaders attacking the body, viruses are the most insidious. They cannot reproduce outside host cells, like bacteria, but must get inside a cell, where they will use the replicatory material (RNA) in the cell to reproduce viruses. This “hijacking” turns healthy cells into “virus factories.” Sometimes the infected cell lyses – bursts – and releases new viruses into the blood, each of which tries to penetrate another cell and repeat the process. Interferon stimulates cells to produce a protein that blocks viral messenger RNA transcription, preventing the virus from replicating and thus protecting the cell from infection. Besides blocking viral replication, interferon can modulate the function of macrophages, T and B cells and natural killer cells. Interferon can inhibit cell proliferation, tumor growth and fibroblast-adipocyte differentiation; it can enhance macrophage phagocytosis, activity of natural killer cells, and endotoxin-induced IL-1 secretion by macrophages.

Colony-stimulating factors (CSF), also cytokines, work in the bone marrow to produce platelets, erythrocytes, neutrophils, monocytes, eosinophils and basophils. GM-CSF stimulates the production of mononuclear phagocytes and granulocytes; G-CSF stimulates the production of granulocyte precursors; IL-3 (produced by T lymphocytes) stimulates all types of cells listed above. The most potent CSF is the newly discovered SCF, which works synergistically with many cytokines promoting the growth of all hematopoietic and lymphoid cells.

Another group of cytokines that have chemoattractant abilities is known as chemokines. These substances differ from other cytokines in that they alter the functioning of a cell but not its growth and are unable to induce the production of other cytokines. Chemokines are capable of attracting fibroblasts and other inflammatory cells to a site of infection. IL-8 is a prominent chemokine found in the blood of patients with systemic infections and septic shock, and in the synovial fluid of patients with arthritis. The role of these chemokines in the overall immune response is still being studied.

Each cytokine has a specific function, but many have overlapping functions and work synergistically. For instance, when the nonspecific cells recognize that a virus is present, type 1 INF, IL-12 and IL-15 are produced to recruit and activate NK cells (which destroy virus and virus infected cells). This is the first line of defense against virus. When bacteria invade the body, TNF, IL-1 and chemokines begin a local inflammatory response against the bacteria. If necessary, IL-6 is produced to fight the bacteria systemically.

Nonspecific immunity begins first, and then the specific immune response gears up, which occurs with the production of IL-2, type 2 INF, TNF-beta (also known as transforming growth factor beta). When needed, other cytokines are produced that begin to turn off the immune response.

EICOSANOIDS

Eicosanoids, produced from fatty acids, have regulatory functions similar to hormones. The difference between an eicosanoid and a hormone is that eicosanoids are produced throughout the body by various cells, while hormones are produced in an organ, then migrate via the blood to the site of action. There are four classes of eicosanoids: prostaglandins (PGs), leukotrienes (LTs), prostacyclins (PCs) and thromboxanes (TXs).

Prostaglandins are produced by macrophages and are involved in the regulation of the immune response, proliferation of lymphocytes and the inflammatory process. Thromboxanes are produced by platelets and macrophages and are involved in platelet aggregation and the formation of blood clots. Thromboxanes have a vasoconstricting effect. Prostacyclins, produced by macrophages, are vasodilators which work to prevent the aggregation of platelets and prevent blood clots.

Leukotrienes are produced by monocytes, neutrophils, macrophages and other white blood cells. These eicosanoids are chemotactic factors controlling the migration of phagocytes and the release of lysosomal enzymes. The inflammatory response is also influenced by leukotrienes.

Cytokines regulate each other by competition, interaction and feedback mechanisms. But it is important to understand that regulation of cytokines is interconnected with other regulatory substances of the body, such as hormones, endorphins and eicosanoids. These substances can inhibit or enhance the effects of cytokines. Because of this, other organs, cells and substances can have a direct effect on the functioning of the immune system.

The therapeutic use of cytokines is being investigated. Many ILs have severe side effects so their use is limited. CSFs have few side effects and are being studied for clinical use. GM-CSF and G-CSF may be of value in preventing granulocytopenia (decreased number of granular leukocytes) caused by radiation and chemotherapy. Drugs commonly used today are neupogen, to increase white blood cell production in cancer, AIDS and other patients with low white blood cell counts. Epogen is given to renal dialysis patients to increase red blood cell production.

How does nutrition enter into the functioning of the immune system? As you will see, nutrition plays a role in the production of cells and substances necessary for proper immune function. Beyond that, nutrition (diet) appears to alter the production of some of the regulatory substances such as cytokines and eicosanoids. If that is the case, then nutrition plays a role in modulating immune function.

CHAPTER TWO: THE IMMUNE RESPONSE

Now that you are familiar with the components of the immune system, let’s put the pieces back together again to see how it functions as a whole.

PHAGOCYTOSIS (NONSPECIFIC IMMUNITY)

An antigen, having evaded all the nonspecific resistance barriers, enters body tissues or the bloodstream. A macrophage or neutrophil encounters the antigen and destroys it by phagocytosis, as illustrated on the next page. This simple process is in reality a series of complex activities.

Macrophages, neutrophils and other granulocytes are attracted to injury sites by chemoattractants, such as IL-8, fibrin or collagen fragments, prostaglandin D2 or platelet-activating factor. Once at the injury site, they are able to identify the bacteria and debris particles they must destroy, but cannot differentiate between foreign antigens, only that the invader is nonself and must be destroyed by phagocytosis.

During phagocytosis, the foreign antigen is bound to the surface of a macrophage, sometimes assisted by C3 complement. The phagocytic cell then engulfs the antigen and brings it into the cell, forming a phagosome – a sort of walled-off compartment within the cell. The destruction of the antigen takes place chemically inside the phagosome. Lysozymal enzymes, free radicals, hydrogen peroxide (in combination with ascorbic acid and copper ions) and lactoferrin are all involved in destroying the antigen. Oxygen is used to produce the lethal free radicals, including nitric oxide, that kill the foreign antigens during phagocytosis. Excess hydrogen peroxide is removed from the cell by enzymes to prevent damage to the phagocytic cell. The remains of the antigen are digested by the phagocyte.

In the course of engulfing the antigens, bactericidal chemicals and free radicals can leak out of the phagocyte and damage nearby cells and tissue of the host organism. Neutrophils, with their lethal bactericidal enzymes, may not live longer than hours or days (macrophages can survive longer); when neutrophils die, their enzymes can damage host tissue.

Phagocytosis

After the antigen is killed, portions of it are displayed on the outer surface of the macrophage. This antigen fragment can now be recognized by T cells. This is how T cells learn to recognize invaders and this begins the specific immune response.

THE SPECIFIC IMMUNE RESPONSE

Unlike phagocytes, lymphocytes have the ability to differentiate between self cells and foreign antigens and distinguish which antigens are their specific target. To understand this process let’s begin with how lymphocytes differentiate between self and nonself.

Every cell has a protein marker, genetically determined by the major histocompatibility complex (MHC), on its surface. These MCH markers have important functions in the immune response. Class I MHC markers identify a cell as “self” so that immune cells will leave them alone. MHC markers also determine which antigens an individual will respond to and how strong the response will be. This accounts for the variance among individuals in their response to viruses, bacteria and reactivity to allergens. MHC markers are also known by another name, human leukocyte antigens or HLA antigens, class I and class II.

Cytotoxic T cells use the class I MHC markers to identify self cells that have been infected by viruses or have mutated. The cytotoxic T cell binds to the class I MHC marker looking for signs of infection or mutation. If found, it destroys the infected cell.

T cells cannot recognize antigens; they must be “shown” what an antigen “looks like,” and what receptor will be needed to bind that specific antigen so it can be destroyed. Class II MHC markers are used by cells that are responsible for presenting antigens to the helper T cells – macrophages, B cells and dendritic cells. These cells are known as antigen presenting cells or APCs. Via phagocytosis, APCs break antigens into short peptides and bind a fragment on the outside of the cell on the MHC marker. The T cell will bind to the antigen fragment displayed on the MHC marker. (Unlike T cells, B cells can recognize antigens in their natural state and they do not need to be broken down by APCs.)

Once the T cell binds to the antigen fragment, it will identify the antigen and the correct receptor needed to bind it. The T cells release cytokines that stimulate production of more T cells with the antigen-specific receptor. This process is shown below.

Recognition of Antigens

Once a lymphocyte or macrophage recognizes the cell by the antigen fragment or the MCH marker on the cell surface, it decides either that the antigen is self and needs no response, or that it is foreign and must be attacked. The receptors on the lymphocyte play a big part in the reactivity of the immune system.

Once a T cell has learned to recognize an antigen marker, it can reproduce T cells with a surface receptor for that antigen. The macrophage thus plays a key role in mounting an immune response by “teaching” T cells which receptor they need for a specific type of antigen which has invaded.

This is a very violent process, and safeguard mechanisms must be built into the system to prevent damage to the host organism from self-reactivity, the overstimu-lation of the immune response.

Lymphocytes are most in need of safeguards since they must be able to recognize foreign molecules and virus-infected body cells. Phagocytosis, lysozyme, interferon and direct activation of C3 complement are defense mechanisms that are normally active against components exclusive to microorganisms and altered or damaged “self” cells and tissue, so they do not need the same safeguards as lymphocytes.

ACTIVATING THE IMMUNE RESPONSE

A binding of the macrophage to the T cell activates the immune response, as illustrated in the diagram on the next page. If the T helper cell has never encountered the antigen on the macrophage, it must create a receptor for it, which delays the activation of the immune response. If the antigen has previously been inside the body, however, it will have been identified and receptors already created for it. This is the theory behind immunization; the introduction of an antigen allows the body to produce a rapid, effective combative response.

As illustrated, the macrophage secretes IL-1, IL-6 and IL-15 which stimulates T and B lymphocytes, natural killer cells, neutrophils and the hypothalamus. At the same time, T helper cells produce IL-2, which stimulates the T cells. Once activated, T cells set into motion a series of events to stimulate the rest of the immune system.

The activated T helper cells stimulate other T cells in the thymus to proliferate or mature. These cells then migrate to tissues where needed, move to other lymphoid organs, or circulate in the blood. Other cytokines are produced: IL-4, IL-5, IL-6 and INF-gamma stimulate B cells, NK cells and granulocytes. Without adequate IL-2, the immune response is impaired.

Activating the Immune System

The T cells then produce cytokines and prostaglandins to orchestrate the cell-mediated immune response and the nonspecific immune response. The production of cytokines directs the actions of the monocytes, macrophages, neutrophils, basophils and eosinophils.

These phagocytic cells begin to multiply and migrate to the site where antigens are present. The monocytes, macrophages and neutrophils kill organisms by phagocytosis. The integrated immune response is shown on the next page.

At the same time the cell-mediated and nonspecific immune response is occurring, the activated T cells migrate to the bone marrow and spleen to activate B cells. The B cells are released into the blood where they develop into plasma cells and begin producing antibodies. The antibodies can migrate into the tissues as necessary.

The Immune Response

Interferon, which prevents the replication of viruses in healthy cells, is produced once the macrophage and T cell begin producing interleukins. Interferon also stimulates other immune cells to help amplify the immune response.

Once antibodies are produced and begin to bind to antigens, complement is produced in the serum. Complement assists antibodies and phagocytes in binding to antigens more quickly and effectively, increasing the ability of the immune system to kill antigens. This is why complement is known as an “attachment promoter.”

When antibodies bind to antigens, they form what are called immune complexes, which then can be phagocytized. Usually phagocytes can clear the tissue or blood of immune complexes. Those that are not cleared stay in circulation and cause inflammatory damage to tissues and organs. Autoimmune diseases may partly be the result of a failure to clear immune complexes – the immune system gets the message that more and stronger response is needed, and creates or continues an unnecessary response.

When antigens are no longer present, T suppressor cells are produced to stop proliferation and growth of cells – to “turn off” the immune response. Memory cells, both T and B, remain after the conclusion of the battle, so that the next time the antigen is present in the body, an immune response can be mounted more quickly because the appropriate receptor is now circulating.

HUMORAL IMMUNITY

The humoral branch of the immune system is made up of immunoglobulin proteins (antibodies) produced by B lymphocytes in response to chemical messages from T helper cells. The B lymphocytes differentiate into plasma cells that produce immunoglobulins secreted into the blood. Their main function is to bind antigens so they can be destroyed by the immunoglobulin or by phagocytic cells.

Unlike T cells that must have antigen fragments presented to them, B lymphocytes can recognize whole antigens. Immunoglobulins are bound to the surface of the B cell and contain antigen receptors. The binding of the antigen provides a signal to B cells and they can become active themselves. However, the B cells need the help of T cells to work effectively. The B cell will display an antigen fragment bound to its MHC class II marker. The T cell binds the antigen fragment and class II MHC marker, and produces cytokines IL-2, IL-4 and IL-6 that signal B cells to reproduce and begin production of mass quantities of antibodies.

Of the five categories of immunoglobulins (IgA, IgG, IgM, IgE and IgD), the most predominant is IgG, comprising 75 percent of the total immunoglobulins found in the body. IgG is the only immunoglobulin that can cross the placenta and is responsible for the immune protection of newborns during the first few months of life. Another role of IgG is to bind and activate complement to enhance the killing of antigens.

IgA accounts for 10 to 15 percent of serum immunoglobulins and is produced by submucosal lymphoid tissues, such as Peyer’s patches in the GI tract, and the tonsils. It is also prevalent in secretions such as saliva, tears, intestinal mucus, bronchial secretions, breast milk and prostatic fluid. The IgA found in secretions is known as secretory IgA.

About 10 percent of serum immunoglobulins consist of IgM; it is more abundant in the early part of the immune response, with the quantity decreasing as the immune response continues. In addition, IgM is also found on the surface of B lymphocytes and assists in the recognition of antigens. Of all the immunoglobulins, IgM is the most effective in activating complement.

IgE is found only in minute amounts in the serum and is involved in the allergic response (described later in this chapter). Individuals with allergies have elevated levels of IgE in their blood. The role of IgD is not as clear as other immunoglobulins. Only trace amounts are found in the blood. The majority of IgD is found on cell surfaces that also have IgM cell surface markers.

Once immunoglobulins are produced for specific antigens, a few B cells with the ability to recognize that particular antigen remain in circulation. The next time that antigen presents itself, the immune response occurs more rapidly.

INFLAMMATION

When the body fights an antigen invasion, we call it infection, which often causes an inflammation. Although painful and distressing, inflammation means that the immune system is working. Inflammation is illustrated below.

Inflammation

When a tissue is injured, cells migrate to the site of injury and infiltrate the tissue. The increased number of cells at one site causes swelling. The production and release of vasoactive amines by the granulocytes, and bactericidal enzymes that leak into the tissues, also cause swelling and heat. Blood platelets, other clotting factors and pro-inflammatory cells are also present at the injury site and can cause swelling.

Once the antigens have been removed, the inflammation begins to decrease, debris is cleared from the site by the blood and/or lymph fluid, the cells die or retreat and healing begins. While inflammation is a sign that the immune system is working, keep in mind that the byproducts of the immune response can become harmful. As the number of immune cells increases, so does the quantity of cytokines produced. Since cytokines act on other organs of the body – hypothalamus, kidneys, lungs, brain, bone – they can have a negative impact on the body’s ability to recover from a major infection if the infection and inflammation are severe.

ASSESSMENT OF THE IMMUNE RESPONSE

Tests have been developed to determine how well the immune system is functioning. These are specific to various functions of the immune system: there are tests that measure cell-mediated immune function and others that measure humoral immune function.

Some tests measure in vivo responses, testing the response in the body itself; others measure the ability of a specific cell to perform a particular function in vitro , which may or may not reflect what is actually occurring in the body. Tests may indicate that one part of the immune system is normal while another part is impaired. It is possible for the number of T cells and phagocytes to be seen as normal, but for migration to the site of the antigen invasion to be deficient. Alternatively, the number of immunoglobulins may be normal, but the T cell count can be low.

The complexity of the immune system (and the difficulty in assessing the strength of a threat) makes it difficult to determine the degree of immunocompetence of the body as a whole. Tests can indicate a deficiency or weakness.

A healthy immune system should act quickly and decisively. Delayed hypersensitivity is an indication of ineffectiveness of cell-mediated immunity. Thus, delayed cutaneous hypersensitivity tests (DHT) also known as delayed hypersensitivity response (DHR) help measure how well the body responds to antigens by developing an inflammation reaction. In this test, the subject is injected intradermally with an antigen extract (such as Candida, streptokinase-streptodornase or mumps extract).

Normally, the body’s lymphocytes respond to the challenge and produce a localized reaction within one or two days. The physical size and appearance of the inflamed area is measured and assessed; a vigorous inflammation that appears quickly and subsides quickly means that the body recognized the threat, brought itself up to combat strength, and disposed of the invaders with dispatch.

A healthy immune system should produce plenty of fighters when it knows an antigen is present. Lymphocyte activation tests determine the ability of T and B cells to proliferate. T and B cells are taken from an individual and incubated in vitro with antigens or mitogens. (Typical antigens are phytohemagglutinin (PHA) or concanavalin A (Con A) for T cells, pokeweed mitogen for T and B cells and lipopolysaccharide for B cells).

When the sensitized lymphocytes encounter an antigen, many complex biochemical and morphological changes occur. Among them are increased phospholipid turnover on the membranes, fatty acyl exchanges on the membrane, increased permeability to cations through the membrane, RNA and protein synthesis and DNA synthesis. Measurement of these biochemical changes will determine how well the lymphocytes are able to proliferate.

For example, the lymphocyte activation test measures the amount of protein synthesis by C leucine incorporation 16 to 24 hours after incubation. More C leucine measured means more protein is synthesized; more protein synthesized means more cells are being produced. A strong positive result indicates a vigorous and healthy response. Another similar measure is DNA synthesis: by measuring H thymidine incorporation into DNA 72 hours after incubation with the antigen, we can determine how well lymphocytes reproduce. Tests can determine what kind of antigen produces the best result, or, conversely, which antigens the body has trouble mobilizing against.

Other tests can measure chemotaxis of cells, the quantity of antibodies, lymphokines, prostaglandins, phagocytes, granulocytes and B cells, and the cytotoxicity of cells. The chart on the next page lists some of the available tests.

It is not necessary to understand the mechanics of all of these tests to know their significance. An underperforming immune system will soon reveal itself. They do give you a measure of how well the immune system is functioning overall, how specific parts are working, and what effect various treatment modalities — and nutrition — can have.

Tests to Assess Immune Function

There is a growing community of people who believe that tests of immune function are also valuable as tests of nutritional status. As we come to understand that nutrient availability is a critical factor in the functioning of the immune system, we see that poor immune function tests can indicate either mechanical problems with immune functions or deficiencies in nutritional status. In later chapters, we’ll see how specific nutrients affect immunity, and explore some of the nutritional links between immune functions and nutrition.

Before progressing to that, however, we need to understand just a bit more of the mechanics of the immune system — or, shall we say, of the malfunctioning immune system.

FAILURES OF THE IMMUNE SYSTEM

When the immune system is functioning suboptimally or defectively, a patient cannot combat an invading pathogen promptly, and manifests illness. He or she may “catch cold,” or have an acute short-term illness (a “24-hour virus” or flu), or suffer from chronic problems caused by a virus, parasite or bacteria: or may develop rashes or more serious conditions. If the immune system is able to strengthen itself and muster its forces, all goes well. The immune system rebounds to fight off the invader, and the person recovers.

This happens more or less continually throughout life: the immune system periodically gears up to respond to a new or renewed threat; sometimes it takes a while to prevail. The patient might say his or her “resistance is down.”

ALLERGIES AND AUTOIMMUNE DISEASES

In some cases, however, the illness stems from the functioning of the immune system itself. In allergies, the immune system responds to a substance that is not inherently harmful. For some reason the immune system perceives pollen, grass, dust, molds, milk, eggs, animal dander, protein, to name a few, as a threat to survival. Common forms of allergies are hay fever, asthma, and food allergies.

Just why this happens is not well understood, but the mechanics of the reaction are. Upon exposure to the usually harmless antigen, the body produces IgE, which attaches to the surface of mast cells in the tissues and basophils in the circulation. When the IgE-mast cell encounters the antigen, it binds to it and releases histamine, which causes a localized inflammation reaction. This can be as minor a problem as a small hive or a minor rash, with swelling and itching, or, more commonly, an inflammation of the eyelids, nostrils, or lining of bronchial tubes, with sneezing, runny nose, congestion, coughing and wheezing. In severe allergies, this response can interfere with respiration or heartbeat.

Fortunately, such severe allergies are rare, and often can be prevented tests for penicillin allergy, for instance, are routinely administered. Usually, the allergenic substance can be identified and avoided, although isolation can be socially and psychologically difficult. Many allergies can be considered an annoying and sometimes incapacitating overreaction. In a manner of speaking, the immune system functions too well — it perceives and reacts to threats that are not there.

However, in more serious autoimmune diseases, the body loses a crucial ability: to separate self from nonself. In some cases, it is known that B cells produce extra antibodies which damage body tissues. An inability of the T suppressor cells to shut off B cell production may be responsible, but the exact causes of the immune system’s attack on the body it is trying to protect are not known.

The most common autoimmune disease in the United States is arthritis, affecting about 3 percent of the population. In arthritis the body produces antibodies (known as autoantibodies) to IgG in the joints. The autoantibodies and IgG bind to form immune complexes that precipitate in the fluid in the joints, causing inflammation, pain and stiffness. Chronic inflammation can lead to loss of range of motion, deformity and destruction of the joints, tendons, cartilage and ligaments.

Other autoimmune diseases also involve the body, producing autoantibodies, and the damage occurs from immune complexes causing inflammation and eventual destruction of the tissue. The following are considered autoimmune diseases: systemic lupus erythematosus (lupus), multiple sclerosis (MS), diabetes mellitus, myasthenia gravis, scleroderma, rheumatic fever, Crohn’s disease, pernicious anemia, glomerulonephritis, Addison’s disease, Graves’ disease and thyroiditis.

There is no cure for these autoimmune diseases, although sometimes systemic treatment can retard or arrest the symptoms. The person must learn to live with them; sometimes they are fatal.

CANCER AND AIDS

Cancer is a more subtle disease, and in strict terminology cannot be considered an autoimmune disease. However, there are similarities, and cancer is increasingly being linked to failure of the immune system.

Among the cells of the immune system we reviewed in Chapter One are natural killer cells, a sort of search-and-destroy team for mutated and initiated cancerous cells. Besides natural killer cells, the body has cytotoxins, interferon, and cytotoxic T cells which destroy cancerous cells.

Everyone has cancerous cells in his/her body, throughout life; mutated cells are constantly being formed, found and destroyed. Why this system breaks down, causing the disease state, is not known. It could be a failure of the immune system, or an increase in the number of mutated cells, which in turn could be caused by dietary, genetic or environmental factors, or a combination of these. No one knows the precise cause of cancer, but it is safe to say that the immune system is involved somehow in our ability to combat it.

Acquired Immune Deficiency Syndrome (AIDS) is a disease specific to the immune system, and as such is the most devastating of threats. The Human Immunodeficiency Virus (HIV) attacks T helper cells (specifically, T4 cells). It also affects macrophages and B cells, and thus causes a multiphased breakdown in the sequence necessary to fight disease. Kaposi’s sarcoma and parasitic infections, normally kept in check quite easily, take advantage of the deficient immune system.

The effect of the HIV virus on T helper cells, which are involved in activating the immune system, is especially devastating. Without the ability to “turn on” or “turn up” the immune response, the individual is left without a means of defending against the most mundane invaders. Invading antigens flourish, and AIDS patients die from diseases such Pneumocystis carinii pneumonia.

(In Nutrition & Immunity Part II I will go into these diseases in more depth, in particular the advances that have been made in understanding the nature of the disease and various treatments, including nutrition and drugs.)

These are extreme cases. Often, people have no failure or malfunction, per se, of the immune system, but may be a bit immunocompromised, and therefore unable to mount a satisfactory immune response. Healing may be impaired, recovery time may be prolonged or the infection may prevail. In these cases, there is nothing really wrong with the immune system; it just cannot fight as well as it should. Malnourished individuals, particularly in hospital settings, often manifest these problems.

The following chapters will consider how important nutrition is to the maintenance and optimal functioning of the immune system.

CHAPTER THREE: NUTRITION’S EFFECT ON THE IMMUNE SYSTEM

Every cell, substance and function of the immune system requires nutrients. Nutrients provide the support necessary for the immune system to mount an immune response. Every component of the immune system appears susceptible to nutritional deficiencies, including such nonspecific responses as phagocytosis and killing activity, as well as cell-mediated and humoral immune functions. Therefore, nutritional deficiencies increase susceptibility to infection.

This chapter discusses the overall relationships of nutrition and immune system functions and shows how malnutrition and infection alter immunity and how infections themselves alter nutritional status.

Much of the information concerning the relationship of nutrition and immunity comes from investigations of malnutrition in Third World countries, where the leading cause of death for children under the age of 5 is infectious diseases, secondary to malnutrition (Chandra, 1991). In Bangladesh, for example, 34 percent of all children die from persistent diarrhea (Baqui, et al., 1993). Nutritional status and cell-mediated immunocompetence are important risk factors for persistent diarrhea.

When these children are infected with measles, mumps, chicken pox, streptococcal or other infectious agents, they are unable to adequately fight the infection. Why? Often, their bodies do not have the calories and nutrients necessary to produce all of the components of immunity. They are unable to mount an effective immune response, the infection takes over the body, and they die.

What we have learned from these studies is that there really is no magic in understanding how malnutrition can impair immunity. All the cells of the immune system discussed in Chapter One are made up of carbohydrates, protein and fat. Every immune system cell must produce energy, get rid of waste, and produce enzymes, surface markers and other tools to fight antigens. These functions require nutrients which, if not available in sufficient quantities, prevent the cell from being produced, impair its ability to function properly or cause it to die. When the body is not producing healthy cells, it cannot mount an immune response.

Understanding the metabolic role of nutrients in the body is the first step. For example, DNA is necessary for cells to proliferate; nutrients required to produce DNA – zinc, phosphate, carbohydrate, nitrogen, niacin (for some nucleotides) – must be available. A deficiency of zinc, for example, could seriously impair the ability of the body to produce lymphocytes and phagocytes, thereby causing immune dysfunction.

Deficiencies, for any reason, affect all components of immunity. Among the causes of the deficiency are an inadequate diet, impaired digestion and/or absorption, altered metabolism, a disease state, increased utilization of a nutrient, increased need for a nutrient.

Excesses of specific nutrients can also alter immune function. Certain nutrients, including fats, zinc, and vitamins C and E, affect various parts of immune function when present in excess quantities.

Nutritional factors can modify the regulation of the immune system and thereby alter its functioning. Fatty acids, the precursors of prostaglandins, can have a profound effect on regulation of immunity.

Some nutrients interact with each other, so a balance of nutrients in the body is important – for example, amino acids and minerals. Specific amino acids that are not required for healthy individuals have been found to be conditionally essential in stressed and septic hospitalized patients. Failure to supply the needed amino acid can cause a decline in protein synthesis of immune system components. Supplementation of one mineral may decrease absorption of another and lower its serum concentration. Examples of minerals that interact with one another are iron, calcium, zinc and copper.

If any of these nutritional problems occur, qualitative and quantitative changes can be seen in immune function, and are summarized in the chart on the next page. The more severe the nutritional problem, the greater its impact on immunity.

Nutritional Problems & Immune Dysfunction

Changes in nonspecific resistance due to nutritional problems involve the skin, mucosal barriers, GI tract permeability, urinary acidity, and production of lysozyme, complement and interferon. All these changes decrease the body’s protection and ability to fight infection.

The organs of the immune system are also affected. All of the lymphoid organs can become smaller, but the thymus is most seriously affected. Since the thymus is the master gland of the immune system, any negative change in that organ will impact the rest of the immune system.

Cell-mediated immunity is susceptible to nutritional problems, causing a quantitative and/or qualitative change in T cells, T helper cells, T suppressor cells, cytotoxic T cells, natural killer cells, macrophages, monocytes, neutrophils, basophils, eosinophils and mast cells. A decrease in the number of cells or impairment of their ability to proliferate is possible. Problems with DNA/RNA synthesis, protein synthesis, or availability of enzymes or cofactors, mean the cell cannot reproduce.

Even if the number of cells is adequate, their ability to function can decline. Cells can be de


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