Deficits or defects in specific immune cells favor specific types of infections. For example, a T-cell deficiency increases your chances of getting bacterial sepsis, CMV, Epstein-Barr, and yeast infections. A B-cell defect or deficiency increases your susceptibility to Streptococci, Staphylococci, Enteroviral encephalitis, intestinal giardiasis, and chronic meningitis (Cotran et al., 1999).
Your general immunological characteristics, such as your ABO blood type, can affect your susceptibility to specific diseases. People with type O blood get more peptic ulcers because the markers on the surface of their blood cells make it easier for H. pylori to attach to their stomach lining (Edwards et al., 2000). Similarly, people with type A blood get more gastric cancer (Bland, 1999).
Because plant proteins called lectins bind to the surface of your cells and act like specific antibodies, there is no doubt that your blood type can also partially determine your individual response to specific herbs. In fact the plants themselves use similar sensitive chemical recognition mechanisms to activate defense-related genes just as we do (Nurnberger et al., 1997). This can certainly help explain why some people react differently to certain herbs and foods than do others, and is a fascinating area for future herbal research.
The Immune System Players and Herbs
Many people still believe that the effects of herbs are either very weak, or can only stimulate or suppress immune function in a general way. We are now learning that individual herbs have powerful and often very specific effects on immune function—another exciting area of natural medicine. The ability to see these effects both in the clinic, with regard to blood tests and patient response, and in the laboratory, is gradually changing our understanding toward greater respect for herbal medicines, awareness of potential dangers, and a desire to understand in greater detail what these medicines are capable of doing. However, it is still true that herbs, because they are complexes, tend to act in multi-faceted ways. Here we will examine the various immune system players, and give examples of herbs that can modify or enhance their actions.
Introducing the Immune System Team
The two arms of the immune system each contain important blood cell players, and important molecular weapons and signaling chemicals. The two most important white blood cell components are lymphocytes and macrophages, and the most important molecular chemical components are antibodies and cytokines. Lymphocyte blood cells work with antibody chemicals to destroy specific antigens (foreign particles) in cellular immunity. Macrophage blood cells work with cytokine chemicals for general destruction of invaders, damaged cells and debris in non-specific immunity. We will call the two branches of the immune system Team Cellular and Team Non-specific.
Cellular Immune System Players
The White Blood Cells of Team Cellular
T lymphocytes (T-cells) are formed in the thymus gland. T-cells comprise 60-70% of the lymphocytes in your blood. Each T-cell contains a genetically programmed receptor that allows it to recognize a specific "bad guy" antigen. Along with neutrophils (see below), T-cell proliferation acts as an aggressive first-strike process. T lymphocytes and neutrophils are the body’s primary specific defenses. There are three basic types of T-cells, which neatly fit into the Vata, Pitta and Kapha overview:
• Killer T-cells (our aggressive Pitta T-cells), travel to the site of a problem, where their cell surface receptors allow them to target and release killing chemicals into our own cells that are damaged, infected or cancerous. They release other chemicals that attract phagocytes to the area, as well as interferons, which prevent viral replication.
• Our Vata-like T-cells, or helper T-cells, work more as messengers, helping the killer T-cells to do their job. They secrete IL-2 (described below) which amplifies the immune response, and "tells" the body to grow more killer T-cells. There are two forms of helper T-cells, called Th1 and Th2. Th1 cells focus on response to bacteria, viruses, fungi, and parasites. Th2 cells focus on allergic reactions.
• Kapha-like suppressor T cells, slowly arrive on the scene, sometimes days or weeks after an infection, where they suppress and turn off the killer T-cells. If suppressor T-cells are low, the inflammation continues and damages the body.
Garlic bulb, katuki rhizome (Picrorhiza kurroa), ginseng root, scute root, astragalus root, shiitake mushroom (Lentinula edodes), cuscuta seed (tu si zi or C. chinensis), pycnogenol (from Pinus maritima) and licorice root are among the many herbs and phytochemicals that have been shown experimentally to activate or modulate T-cells (Baylor et al. 1992, Kim KH et al., 1998, Lau et al., 1991, Liu et al. 1998, Sinha et al., 1998, Tang Z et al. 1997, Utsunomiya et al., 1997, Yamamoto et al., 1997, Zhao KS et al., 1990).
B lymphocytes (B-cells) are produced in the bone marrow (of adults) and distributed to outlying lymph tissue (spleen, tonsils, gastrointestinal tract, etc). They constitute 10-20% of the lymphocyte population in the blood. When some B-cells encounter and bind to foreign antigens, they are activated and transform into plasma cells, which produce a vast amount of antibodies (IgG, IgA, IgE etc.) specific to that particular invader. Other B-cells transform into memory cells, which patrol the body for the next appearance of the bad guy antigen so they can signal a quick response.
Licorice root, ginseng root, ashwaghanda root, Siberian ginseng root bark, astragalus root, oldenlandia (bai hua she she cao or O. diffusa), pycnogenol, carthamus flower, and several types of seaweed (particularly Hizikia fusiformis, a kind of algae, and Meristotheca papulosa) have been shown experimentally to modulate the activity of B-cells (Kawakita et al., 1987, Kupin et al., 1986, Liu FJ et al., 1998, Liu JN et al., 1997, Shohat et al., 1978, Wakabayashi et al. 1997, Yang G et al., 1990, Yoshida et al., 1997).
The Chemicals Used by Team Cellular
Antibodies are specific immunoglobulin proteins that act against the foreign substances called antigens. The antibody attaches to the invader creating an antibody-antigen complex, after which it stimulates the immune system to recognize the invader. Think of the antibody as the "neighborhood watch" member who grabs a criminal in the street, holds on and yells for the police. Antibody response can be either primary, occurring at the first exposure to an antigen, or secondary, after exposure to the same or similar antigen at a later date. This is called sensitization. It is the reason why certain pollens, for example, only affect people who have become sensitized. The most common antibodies tested for by physicians are called IgG, IgA, and IgE. High levels in the blood indicate you are fighting an invader.
A few of the many herbs shown experimentally to modulate antibody response include rehmannia root, cuscuta seed, punarnava root (Boerhavia diffusa), echinacea root, golden seal root, cordyceps mushroom, ginseng root, berberine (from Berberis species plants), bitter melon (Momordica charanta), ziziphus seed (suan sao ren or Z. spinosa), cowhage seeds (kapikachu or Mucuna pruriens) and guduchi stem (Tinospora cordifolia). (Ivanovska et al., 1996, Lee YS et al. 1997, Leung et al., 1987, Mathew and Kuttan, 1999, Mungantiwar et al., 1999, Rehman et al. 1999, Yoshikawa M et al., 1997, Aguiyi et al., 1999).
In one dramatic (but unreplicated) study, a TCM formula containing leonorus (yi mu cao or L. heterophyllus), white peony root, banksia rose (Rosa banksia - a variety of rose petal), angelica root (bai zhi or A. archangelica) and Sichuan lovage root (Ligusticum chuanxiong) was shown to prevent hemolytic disease caused by maternal-fetal blood group (Rh-type) incompatibility (Bian et al., 1998).
• IgA (Immunoglobulin type A) is an antibody found primarily in the secretions of mucosal surfaces including those of the upper respiratory tract and the digestive tract, and in tears. There is IgA in mother's milk, which helps protect the delicate upper respiratory and gastrointestinal tract of infants. Consequently, breast-feeding helps protect against allergies and infections. Think of IgA as the "neighborhood watch" guy or gal who signals the immune system at the first sign of the landing of an invader on the surface of your mucous membranes.
Degradation of the epithelial membrane surfaces in the mouth, lungs and intestinal tract can lead to IgA reduction, increasing invasive capacity of foreign proteins and microbes, so the key strategy here is to maintain membrane health.
Scute root, and licorice root increase IgA supply (Smol’ianinov, et al, 1997, Dharmananda, 1988). Carotenes and vitamin A are essential for IgA. A TCM Yin-tonifying formula containing cornus fruit (shan zhu yu or C. officinalis), dioscorea, moutan, poria mushroom, cooked rehmannia root, water plantain rhizome (ze xie or Alisma plantago-aquatica ), schisandra berry, and honey-fried astragalus root has been shown to significantly stimulate small intestine IgA secretion in an animal model (Sakushima et al., 1997).
• IgG (Immunoglobulin type G) is the most abundant antibody in the blood serum, comprising about 60-70% of the total. In the early stages of infection, increasing IgG can improve the speed of the immune response. In many cases of chronic inflammation and allergy it is important to modulate IgG response downward to reduce the inflammation.
White atractylodes, licorice root, kochia fruit (Di fu zi / Kochia scoparia) and guduchi stem have been shown to modulate IgG response (Chang, et al., 1997, Kapil and Sharma, 1997, Matsuda, et al, 1997, Dharmananda, 1988). Long-term oral administration of ginseng root extracts has also been shown in animal experiments to decrease certain subtypes of IgG, such as IgG1, IgG2a, IgG2b, and IgG3 (Kim YW, et al., 1997). Additionally, a clinical trial of the traditional treatment for the common cold, using echinacea root and golden seal root (Hydrastis canadensis), increased production of IgG and IgM (Rehman, et al, 1999).
• IgE (Immunoglobulin type E) is found primarily in the linings of the respiratory and intestinal tract. It binds to mast cells and basophils and stimulates the release of inflammatory substances (such as histamine), making it the most common "neighborhood watch" member concerned with allergic reactions.
Echinacea, garlic bulb, ginkgo leaf, feverfew, golden seal root, er bu shir tsao herb (Centipeda minima), rehmannia root, salvia root and turmeric root are among the many herbs that may reduce or inhibit IgE-mediated allergic reactions (Kim HM, et al, 1998, Duke, 1999, Kobayashi et al., 1997, Wu et. al, 1991). In one study, a water extract of an herbal formula prepared from the very cold TCM herbs scute root, coptis rhizome (C. japonica), phellodendron bark and gardenia fruit (zhi zi or G. jasminoides) suppressed anaphylactic histamine release in a dose-dependent manner (Kim and Park, 1998). However, these herbs cannot be used directly as alternatives to antihistamines. This will not work. Rather, allergy must be treated in a comprehensive way using herbs as part of the total picture. Use of strongl drugs or steroids to treat allergies via simple suppression often fails over the long term.
Non-specific Immunity Players
The Blood Cells of Team Non-specific
Phagocyte is a general term for the white blood cells that engulfs and digests foreign bodies in a non-specific manner (a process called phagocytosis). These cells are either chemically attracted to sites of inflammation by the release of histamine and other messengers into the blood, or lay in wait at specific locations. They are easiest to understand if you think of them as vacuum cleaners or vultures. There are two types based upon size-- smaller microphages, which primarily ingest bacteria, and the larger macrophages, which gobble up and digest dead tissue and cellular debris. Phagocytes also release pyrogens, which induce fever in response to infection Monocytes, the precursors of macrophages, comprise about 3-7% of the circulating white blood cells.
Macrophages are actually monocytes that have taken up residence in specific tissue areas such as the liver, spleen, connective tissue or lymph nodes. Physicians give them different names, depending on where they live. In the liver they are called Kupffer cells; in the skin, they are called Langerhans cells; in the spleen and lymph nodes they are called dendritic cells; in the lung they are called alveolar macrophages; in the connective tissue they are called histiocytes; in the brain they are called microglia.
Macrophages are capable of fusing together into huge granulomas to combat and engulf larger pathogens. All the above-mentioned phagocytic cells are collectively known as the reticulo-endothelial system (RES).
Many, many herbs have been shown to increase the numbers and action of phagocytes, including ginseng root, rehmannia root, isatis root, codonopsis root (dang shen), mistletoe (Viscum album), cordyceps mushroom, cat's claw inner bark (Uncaria tomentosa), licorice root, astragalus root, celosia seed, guduchi stem, ashwaghanda root, olive leaf extract, garlic bulb, ganoderma mushroom, Siberian eleuthero root bark, maitake mushroom, lycium fruit, white atractylodes and echinacea (Bussing et al, 1999; Stein et al, 1999; Chen YJ, et al, 1997; Sonoda, et al, 1998; Dharmananda, 1988; Xie, et al, 1985; Hase, et al, 1997; Hayakawa, et al, 1998; Kapil and Sharma, 1997; Kumar VP, et al, 1999; Lee YS, et al, 1997; Lemaire, et al, 1999; Mathew and Kuttan 1999; Nose, et al, 1998; Rittenhouse, et al, 1991; Rui, 1997; Visioli et al, 1998).
According to a systematic study of more than 200 TCM herbs and formulas used for Qi energy tonification, all had the ability to increase the phagocytic index of the RES from two to five times above normal (Wenlong, 1994).
Natural Killer (NK) cells make up approximately 15% of all circulating white blood cells. They roam the body and are capable of acting spontaneously, rather than in response to orders from other immune components (such as antibodies). Individual NK cells are like Dirty Harry. More deadly than even cytotoxic T- cells, NK cells are very important first line fighters of cancer and AIDS. In fact, the level of NK activity is a good estimator of chances of survival in these types of deadly diseases. NK cells release interferons, chemicals which interfere with viral replication. A weakening or cessation of function in NK cells indicates that death is near.
Many herbs, especially medicinal mushrooms like maitake mushroom, ganoderma mushroom, and shiitake mushroom are known to strongly increase NK cell activity (Kurashige et al., 1997, Won et al. 1992, Yamamoto et al., 1997). Other herbs that stimulate NK cell function include celosia seeds, licorice root, garlic bulb, ziziphus fruit, ginseng root, gymnostemma (jiao gulan or G. pentaphyllum), Western larch bark and mistletoe (Lamm and Riggs, 2000, Kamei, et al, 1998, Kelly, 1999, Schink and Bussing, 1997, Tang et al., 1997, Yamaoka et al., 1996, Dharmananda, 1988, Yang et al., 1990, Zhang C et al., 1990).
Neutrophils are short-lived cells stored in the bone marrow and called into action to prevent and treat bacterial infections. These aggressive cells engulf and destroy bacteria, fungi, parasites, foreign particulate matter and cancerous cells, destroying themselves in the process. Think of them as the body’s kamikaze cells.
Garlic oil, ginseng root, guduchi stem, shiitake mushroom, black cumin seed (krisnajirakam or Nigella sativa) and mistletoe have been shown to increase neutrophil activity. Cooling herbs like scrophularia root (xuan shen or S. ningpoensis ) reduce neutrophil activity, an important mechanism for controlling some inflammations (Akamatsu et al., 1998, Fernandez et al., 1998, Gao et al., 1993, Nabil H et al., 1998, Sonoda et al., 1998, Thatte et al., 1994, Timoshenko et al., 1998, Sia et al., 1999).
Eosinophils and basophils, like other immune cells, secrete a wide variety of toxic chemicals that break down and destroy antigen-antibody complexes related to allergy. Basophils, for example, release heparin and histamine. Eosinophils release several major basic proteins, eosinophil cationic protein, eosinophil-derived neurotoxin and eosinophil peroxidase. All of these chemicals can cause tissue injury in prolonged inflammation.
Boswellia gum, ephedra, feverfew, perilla leaves, and turmeric root extract all affect eosinophil function, as does the patent medicine Pe Min Kan Wan and several other TCM classical formulas (Williams CA et al., 1999, Bao L et al. 1997, Gupta I et al., 1998, Ishihara et al., 1999, Kaneko et al., 1999, Kobayashi et al., 1997, Tahara et al., 2000, Ohta Y et al., 1999, Aizawa et al., 1999, Tohda et al., 1999).
The TCM Minor Bluegreen Dragon formula—composed of ephedra, cinnamon twigs, ginger root, Chinese wild ginger (xi xin or Asarum sieboldii), schisandra berry, white peony root, pinellia tuber and licorice root—has been shown to significantly down-regulate eosinophils in animal studies (Okubo et al., 1997, Sakaguchi, et al, 1999). In an article appearing in the journal Carcinogenesis, the combination of an antiobiotic (ampicillin) and Minor Bupleurum Decoction, (bupleurum root, scute root, pinellia tuber, ginger root, ginseng root and jujube fruit) was tested for its effect on lung cancer formation in rats given a cancer-causing chemical. The combination was found to inhibit cancer formation completely (Tsutsumi et al., 2000).
• Mast cells are tissue based cells which that have an affinity for blood vessels. They are activated when antigens bind to their surface IgE receptors, causing allergic reactions. Like basophils, they release histamine and other chemicals that increase vascular permeability and allow other immune cells and complement to enter the tissues from the blood stream. In chronic allergic situations, it is important to stabilize mast cell activity.
Among the many, many herbs which seem to help stabilize or inhibit the activity of mast cells are shilajatu, aguru wood, licorice root, ganoderma mushroom, ginkgo leaf, cooked rehmannia root, er bu shir tsao herb (Centipeda minima) , lavender oil, xi xian cao herb (Siegesbeckia pubescens), gunja seed (Abrus precatorius), katuki rhizome (Picrorhiza kurroa), salvia root, devadaru (Cedrus deodara), aged garlic extract, andrographis (chuan xin lian or A. paniculata), vasaca leaf (Adhatoda vasica), and milk thistle seed. (Ghosal, 1988, Wu JB, et al, 1999, Dharmananda, 1988, Dorsch et al., 1991, Gupta PP et al., 1997, Gupta PP et al., 1998, Kang et al., 1997, Kim H et al. 1998, Boik, 1995 Kim HM et al., 1999, Kim HM et al., 1999, Kim YC et al., 1997, Kyo E et al., 1997, Shinde et al., 1999.).
In one study, the phytochemicals luteolin, baicalein and quercetin were shown to inhibit the release of histamine, leukotrienes, and other immune chemicals from mast cells in a dose-dependent manner. Luteolin was the most potent (Kimata et al., 2000). Dr. Duke's database reveals that luteolin is found in many anti-inflammatory plants, including celery seed (Apium graveolins), water plantain, wild indigo, arjuna bark, buddleia flowers, echinacea, ginkgo leaf, devil's claw root, flaxseed, honeysuckle flower, peppermint leaf, and grapes.
The Molecules Used by Team Non-Specific
Immune response involves multiple interactions between phagocytes, NK cells, basophils, neutrophils etc. Many of these responses happen from cell-to-cell contact. Nearby, however, interactions depend upon immune system messenger molecules called cytokines. The number of these chemicals is huge. Among the things they do are: attack viruses, initiate non-specific anti-inflammatory effects, up-regulate immune response, down-regulate immune response, activate immune cells, attract immune cells, stimulate blood cell formation, interfere with viral replication etc. Cytokines secreted by monocytes are called monokines, and cytokines secreted by lymphocytes are called lymphokines.
As you might expect, many herbs affect cytokines in general and specific ways. Among the herbs that affect cytokines are several from the Immunity/Longevity group—ginseng root, mistletoe, cooked rehmannia root, astragalus root, garlic bulb, numerous medicinal mushrooms, marine algae, and echinacea, among others (Burger et al. 1997, Gao QP et al., 1997, Hajto et al., 1999, Hirabayashi T et al., 1995, Huang 1999, Kim KH et al., 1998, Kyo E et al. 1988, Liu F et al., 1999, Murayama T et al., 1992, Nakano T et al., 1997, Teucher T et al., 1996, Wang SY et al., 1997).
• Interferons are chemicals secreted by cells as a result of viral infection. These chemicals signal the killer T cells to increase activity, and, as their name implies, also interfere with viral replication and help non-infected cells resist viral penetration. There are three primary classes of interferons, called alpha, beta and gamma, as well as various subsets. Most cells can secrete interferon. Think of them as immune system bullhorns.
Herbs that have been shown to directly affect interferon include ginseng root, garlic bulb, mistletoe, ashwaghanda root, noni fruit (Morinda citrifolia) and numerous herbal formulas (Matsumoto and Yamada, 2000, Lamm and Riggs, 2000 , Mori K et al., 2000, Stein GM et al., 1999, Davis and Kuttan, 1999, Hirazumi and Furusawa, 1999, and Smolina et al., 1998).
• Interleukins are proteins that stimulate white blood cell activity. There are dozens of different kinds of interleukins. Think of them as immune system coffee. Interleukin-1 helps produce fever. Interleukin-2, also known as T-cell growth factor, is very important. This is because it not only stimulates T-cell production, but also exerts potent effects related to nerve cell growth, survival, and bioelectric activities
Herbs or herbal extracts shown to modulate production of interleukins, by themselves or in formulas, include ginseng root, astragalus root, bupleurum root, cordyceps mushroom, mistletoe, ashwaghanda root, rehmannia root, garlic bulb, celosia seeds, sophora flower (huai hua mi or S. japonica ), black cumin seed, and cat's claw inner bark. (Matsumoto and Yamada, 2000, Yang and Wu, 1998, Mori K et al., 1999, Matsumoto T et al., 2000, Yamashiki M et al., 2000, Stein et al., 1999, Qun L et al., 1999, Davis and Kuttan, 1999, Yang LY et al., 1999, Iijima et al., 1999, Sakurai eet al., 1999, Kim HM et al., 1999, Min B et al., 1999, Haq A et al., 1999, Kuo YC et al., 1999, Lemaire et al., 1999, Tang Z et al., 1997, Nakajima S et al., 1998, Hayakawa Y et al., 1998).
• Complement is a group of blood proteins that helps to destroy invaders. Complement works like a tag team, and each protein is released sequentially. Complement proteins attach macrophages or neutrophils to antigen-antibody complexes. Think of it as if someone is chaining the watchdog to a burglar in the house. The complement cascade also is capable of punching holes into the invader.
Medicinal mushrooms that contain beta-glucan, such as ganoderma and maitake, enhance complement activity (Ross GD, et al, 1999). Herbs containing rosmarinic acid, such as prunella (xie ku cao or P. vulgaris) and bugleweed (Lycopus virginicus) inhibit complement activation. The heartwood of su mu (Caesalpinia sappan), used traditionally in China to reduce swelling, pain and numbness, also inhibits complement activation (Oh et al., 1998, Al-Sereiti et al., 1999, Arvind et al., 1999).
• Tumor Necrosis Factor (TNF) is a chemical released by macrophages (TNF-alpha), and activated T-cells (TNF-beta). It causes fever, and can kill some types of cancer cells by attacking their blood vessels. Other variegated systemic effects include increased sleep, and decreased appetite. In some cases of cancer, overproduction of TNF-alpha leads to cachexia, a pathological state of appetite suppression and weight loss.
Dandelion root, ginseng root extracts, mistletoe, several types of seaweed, garlic root and aged garlic extract, scute root, schizonepeta (jing jie or S. tenuifolia), carthamus flower and ganoderma mushrooms have been found to stimulate TNF. Conversely in animal and pharmacological models, green tea, cooked rehmannia root, coptis root, milk thistle seed extract, ashwaghanda root, and turmeric root extract (3 different compounds) were all found to inhibit either TNF-alpha production and/or block some of TNF's inflammatory actions. (Lamm and Riggs, 2000, Manna et al., 1999, Shin et al., 1999, Davis and Kuttan, 1999, Gupta and Ghosh, 1999, Plummer et al., 1999, Fujiki H, 1999, Kim HM et al., 1999, Smolina TP et al., 1998, Abe et al., 1999, Bouic et al., 1999, Cho JY, 1999, Kimura Y et a., 1997, Kyo E et al. 1998, Lee HJ et al. 1998, Mannel DN et al., 1991, Plohmann B et al. 1997, Shan BE et al., 1999, Wang SY et al., 1997).