It‚s Time to Rethink Immunity
April 15, 2020
Did you ever wonder why some people never get sick while others get sick often? If so, you‚re not alone. Consider that the average North American adult is stricken with 2 to 4 colds and children contract an average of 6 to 8 bouts of illness during cold and flu season. If you‚re sick this often or more, it‚s a good sign that your immune system‚s germ-fighting powers are low.1 However, it‚s not your fault‚well, mostly. A 2017 study from King‚s College London reveals that genes influence nearly three-quarters of immune traits. The study published on January 5, 2017, in Nature Communications, adds to a growing body of evidence that the genetic influence on our immune system is significantly higher than previously thought. Before we get into the Kings College study, it‚s essential to distinguish between two mechanisms that govern your immune system, immunological response and parts of the immune system. The immune system is typically divided into two categories‚innate and adaptive‚although these distinctions are not mutually exclusive.
INNATE IMMUNITYInnate immunity refers to nonspecific defense mechanisms that come into play immediately or within hours of an antigen‚s appearance in the body. These mechanisms include physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body. The chemical properties of the antigen activate the innate immune response.
ADAPTIVE IMMUNITYAdaptive immunity refers to antigen-specific immune response. The adaptive immune response is more complicated than innate. The antigen first must be processed and recognized. Once an antigen is identified, the adaptive immune system creates an army of immune cells specifically designed to attack that antigen. Adaptive immunity also includes a ‚memory‚ that makes future responses against a specific antigen more efficient.2 Immunological response: a bodily defense reaction that recognizes an invading substance (an antigen such as a virus, fungus, specific bacteria or transplanted organ) and produces antibodies against that antigen.
GUARDIANS OF THE GALAXY: Parts of the immune systemSkin and mucous membranes: are the body‚s first line of defense against infection and disease. The skin prevents most germs from getting into the body. But a cut or burn on the skin can allow germs to get in. Germs can also get into the body through any opening in the body, such as the mouth, nose, throat, anus or vagina. Mucous membranes that line many parts of these openings help to protect the body. Cells of the mucous membrane also make fluids and substances that help destroy germs. And in some areas of the body, mucous membranes are acidic, which also helps prevent infection from bacteria and other micro-organisms. Bone marrow: (part of your lymphatic system) is the soft, spongy area inside of most bones, where blood cells are born. Many of the blood cells in the bone marrow are not fully developed (are immature) and are called stem cells. Stem cells change and grow into different types of cells, including blood cells. Most blood cells grow and mature in the bone marrow. Most blood cells leave the bone marrow and move into the circulating blood and other areas of the body, like the lymph nodes and tonsils, once they are mature. Lymphocytes or NK cells: are white blood cells found in the blood and lymphatic system. They attack viruses, bacteria and other foreign invaders. There are different types of white blood cells, but lymphocytes have the most important role in the immune response. Lymphocytes are also called immune cells or NK Cells. The lymphatic system includes the tonsils, spleen, thymus, lymph nodes, lymph vessels and bone marrow. T cells: (also called T lymphocytes) destroy damaged and infected cells in the body and tell B cells to make antibodies. B cells: (also called B lymphocytes) can turn into plasma cells that make antibodies which help fight infection and disease. B cells can also remember the types of infection and disease the body has fought against in the past. If the same germ gets into the body, B cells can quickly make more antibodies to help fight it, so you don‚t get sick. Dendritic cells: (DCs), named for their probing, ‚òtree-like‚ or dendritic shapes, are responsible for the initiation of adaptive immune responses and hence function as the ‚òsentinels‚ of the immune system. Macrophages: are specialized cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms. In addition, they can also present antigens to T cells and initiate inflammation by releasing molecules (known as cytokines) that activate other cells. Antibodies: (also called immunoglobulins) are proteins made by B cells that have turned into plasma cells. Antibodies travel around in the blood. They fight infection and defend the body against harmful foreign substances by recognizing and binding to a substance (like a germ) that is causing the body to have an immune response. The foreign substances or germs that antibodies bind to are called antigens. A specific antibody is made by plasma cells to fight a specific antigen. An antibody binds to an antigen like a lock and key. So only an antibody made against a specific antigen can bind to it, much like a key can only open a specific lock. When this happens, white blood cells can find and destroy the substance that is causing an infection or disease.
KING'S COLLEGE STUDYResearchers from King‚s, supported by the NIHR Biomedical Research Centre at Guy‚s and St Thomas‚ Foundation Trust and King‚s College London, analyzed 23,000 immune traits in 497 adult female twins. 76% of these traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, Œ≥Œ¥ T cells and NKT cells, whereas dendritic cells, B2 cells, CD4+T and CD8+ T cells are more influenced by genetics. Although leukocyte subsets are influenced by genetics and environment, adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment. They found that adaptive immune traits‚the more complex responses that develop after exposure to a specific pathogen, such as chickenpox‚are mostly influenced by genetics. They also highlight the importance of environmental influences such as our diet, on shaping the innate immunity (the simple core immune response found in all animals) in adult life. Professor Tim Spector, Director of the TwinsUK Registry at King‚s College London said: ‚òOur results surprisingly showed how most immune responses are genetic, very personalized and finely tuned. What this means is that we are likely to respond in a very individualized way to an infection such as a virus‚or an allergen such as a house dust mite causing asthma. This may have big implications for future personalized therapy.3 So, if three quarters of your immune traits are influenced by genetics, you have the opportunity to influence and manipulate a quarter of your immune traits and perhaps dictate more based on diet, exercise, sleep, stress, hygiene, gut flora, alcohol intake, smoking and sugar consumption. You have to look at controllable immunity like a point system. You gain or lose points by how poor or how well you manage the above.
THE IMMUNE SYSTEM AND CANCERCancers of the immune system include lymphomas and leukemias, which are also types of blood cancer. But all types of cancer affect the body‚s immune system. Cancer cells develop from our own cells, so our immune system doesn‚t always know that it should attack them. Sometimes the immune system knows that cancer cells shouldn‚t be there, but more often our immune system doesn‚t notice cancer cells. Cancer cells can even turn off the immune response so that the immune cells don‚t attack them. Also, people with cancer often have a weakened immune system. The immune system gets weakened when the cancer itself or cancer treatment, like chemotherapy or radiation therapy, affects the bone marrow. Blood cells are made in the bone marrow and when it‚s affected by cancer or its treatment, the number of blood cells that are made are lower than normal. When blood cell counts are low, the body can‚t fight off an infection very well.4
ARE WE INNATELY IMMUNE TO CANCER?At some level, yes, and new therapies could boost the body‚s natural anti-cancer responses. Today, we have a great deal of supporting evidence for the importance of NK cells and the innate response in protection from cancer. Cancer cells are constantly arising in our bodies as a consequence of random genetic mutations, some of which give a cell a survival or proliferation advantage. These random changes are mostly novel and have never been presented to the adaptive immune system. The only cells able to detect the ‚stress‚ signals of a tumor cell that is dividing too frequently are NK cells, which can eliminate tumor cells before they become a clinically detectable cancer. A Japanese study published in 2000 measured the resting NK cell response to a single cancer cell line in over 3,500 healthy people on a single day of their life, and then followed them all for over 11 years. Those with the weakest resting NK cell function on the single day that they were tested had a statistically significantly increased incidence of succumbing to any form of cancer over the period of follow-up. The importance of innate immune surveillance is also seen in NK cell‚ìdeficient mice, which generate malignant lymphomas spontaneously. Far from being the poor, unsophisticated relative of the adaptive immune response, innate immunity is central to survival. As we increase our understanding of the innate immune response, we discover how to best manipulate it.5
16% OF CANCERS ARE CAUSED BY VIRUSES OR BACTERIAStrictly speaking, cancer is not contagious. But a fair number of cancers are clearly caused by viral or bacterial infections: lymphomas can be triggered by the Epstein-Barr virus, which also causes mononucleosis. Liver cancers can be caused by Hepatitis B and C. Cervical cancers can be caused by human papillomavirus, the major reason behind the development of a vaccine against it. For some of these cancers, nearly 100% of the cases have an infectious link. When researchers check to see if a virus or bacterium is working in the tumor or has left signs of its presence in a patient‚s blood, the answer is nearly always yes. The Lancet takes a look at the very best data on the prevalence of infection-caused cancers and comes up with some striking numbers. Overall, they estimate that 16% of cancer cases worldwide in 2008 had an infectious cause‚2 million out of 12.7 million. Hepatitis B and C, HPV, and Helicobacter pylori, a bacterium that triggers stomach cancer, caused the lion‚s share of those cases, about 1.9 million together. Eighty percent of all infection-caused cancers were in less developed regions, where vaccines and treatments for these infections may be harder to come by, and sometimes the numbers are shocking: in China, more than a quarter of cancer cases were infectious in origin. Still, a decent fraction were found in the developed world, indicating that the problem hasn‚t disappeared with current advances. And because this paper only looked at infectious agents that are clearly carcinogenic, avoiding those there isn‚t much data on, 2 million cases total is probably something of an underestimate. How many deaths from cancer are caused by these infections? The researchers didn‚t have the data to answer that question rigorously, but they point out that most of the infection-caused cancers are pretty lethal. They make a rough extrapolation from their data and estimate that of the 7.5 million deaths from cancer in 2008, 1.5 million, or about one in five, were caused by an infection.6 The immune system defends the body against infection and disease. Some parts of the immune system look for unhealthy cells or something foreign to the body, some send messages to other cells in the body about an attack and others work to attack and destroy micro-organisms that cause infections‚like bacteria, viruses, fungi, parasites‚or unhealthy cells, like cancer cells again, when the immune system is defending the body against infection and disease, it is called the immune response.
PROTECTORS OF THE REALM: Immune BoostersAntioxidants: A diet that is low in the consumption of fruits and vegetables has long been associated with increased susceptibility to infectious disease. The increase in severity from and susceptibility to infectious disease in malnourished hosts is thought to be the result of an impaired immune response. For example, malnutrition could influence the immune response by inducing a less effective ability to manage the challenge of an infectious disease. Work in our laboratory has demonstrated that not only is the host affected by the nutritional deficiency, but the invading pathogen is as well. Using a deficiency in selenium (Se) as a model system, mice deficient in Se were more susceptible to infection with coxsackievirus, as well as with influenza virus. Se-deficient mice develop myocarditis when infected with a normally benign strain of coxsackievirus. They also develop severe pneumonitis when infected with a mild strain of influenza virus. The immune system was altered in the Se-deficient animals, as was the viral pathogen itself. Sequencing of viral isolates recovered from Se-deficient mice demonstrated mutations in the viral genome of both coxsackievirus and influenza virus. These changes in the viral genome are associated with the increased pathogenesis of the virus. The antioxidant selenoenzyme, glutathione peroxidase-1, was found to be critically important, as glutathione peroxidase knockout mice developed myocarditis, similar to the Se-deficient mice, when infected with the benign strain of myocarditis. This work points to the importance of host nutrition in not only optimizing the host immune response, but also in preventing viral mutations which could increase the viral pathogenicity.7 Beta-Glucans: The healing and immunostimulating properties of mushrooms have been known for thousands of years in the Eastern countries. These mushrooms contain biologically active polysaccharides that mostly belong to the group of beta-glucans. These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. Beta-Glucans also show anticarcinogenic activity. They can prevent oncogenesis (the development of a tumor or tumors) due to the protective effect against potent genotoxic carcinogens. As an immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, beta-glucan can inhibit tumor growth in the promotion stage too. Anti-angiogenesis can be one of the pathways through which beta-glucans can reduce tumor proliferation and prevent tumor metastasis. Beta-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated a positive role in the restoration of hematopoiesis following bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These antibodies activate complement system and opsonize tumor cells with iC3b fragment. In contrast to microorganisms, tumor cells, as well as other host cells, lack beta-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism could be induced in the presence of beta-glucans.8 Astragalus: has a long history of use in traditional Chinese medicine (TCM), and is often used along with other herbs as a tonic to increase stamina, strength, and vitality. Extracts of astragalus are sold as dietary supplements to improve immune function and to decrease fatigue. Beneficial effects of astragalus are attributed to its polysaccharides and triterpenoid saponin compounds. In vitro and animal studies indicate that astragalus and its constituents have antioxidant, anti-inflammatory, and antiviral activities, along with exerting protective effects on the heart, kidney, bones, and the nervous system. Preclinical studies showed the anticancer properties of astragalus against gastric, colon, hepatic and ovarian cancers. Clinical data are limited but astragalus has been associated with prolonged survival times in acute myeloid leukemia patients, and data suggest beneficial effects when used with chemotherapy. Also, injectable forms of astragalus may alleviate cancer symptoms and improve quality of life in patients with advanced and metastatic cancers, but whether orally administered astragalus exerts similar effects is not known. In another study, an astragalus extract helped to manage cancer-related fatigue. Meta-analyses suggest astragalus to be associated with reductions in chemotherapy-induced nausea and vomiting, and to have benefits in patients with hepatocellular cancers.9 Larch Arabinogalactan: The common cold is a viral infection with important economic burdens in Western countries. The research and development of nutritional solutions to reduce the incidence and severity of colds today is a major focus of interest, and larch arabinogalactan seems to be a promising supportive agent. Arabinogalactan has been consumed by humans for thousands of years and is found in a variety of common vegetables as well as in medicinal herbs. The major commercial sources of this long, densely branched, high-molecular-weight polysaccharide are North American larch trees. In cell and animal models, larch arabinogalactan is capable of enhancing natural killer cells and macrophages as well as the secretion of pro-inflammatory cytokines. In humans a clinical study demonstrated that larch arabinogalactan increased the body‚s potential to defend against common cold infection. Larch arabinogalactan decreased the incidence of cold episodes by 23 %.10 Immunoglobulins: also known as antibodies, are glycoprotein molecules produced by plasma cells (white blood cells). They act as a critical part of the immune response by specifically recognizing and binding to particular antigens, such as bacteria or viruses, and aiding in their destruction. The antibody immune response is highly complex and exceedingly specific. The various immunoglobulin classes and subclasses (isotypes) differ in their biological features, structure, target specificity and distribution. Hence, the assessment of the immunoglobulin isotype can provide useful insight into complex humoral immune response. Assessment and knowledge of immunoglobulin structure and classes is also important for selection and preparation of antibodies as tools for immunoassays and other detection applications.11 Probiotics: Beyond simply keeping bad bacteria in the gut at bay, probiotics play a role in defining and maintaining the delicate balance between necessary and excessive defense mechanisms including innate and adaptive immune responses. Points of interaction with the immune regulation for probiotics include bacteria direct interaction with intestinal epithelial cells, or following internalization by M cells through interaction with dendritic cells and follicle-associated epithelial cells, initiating responses mediated by macrophages and T and B lymphocytes. Regulation of gene expression and signaling pathways in the host cells are two major mechanisms underlying probiotic action leading to immunomodulation.12 Gigartina: is a plentiful source of protein, vitamins, trace minerals and fiber. Many species of marine algae including gigartina contain significant quantities of complex structural sulfated polysaccharides that have been shown to inhibit the replication of enveloped viruses including members of the flavivirus.13a The gigartina strain of red marine algae is the richest known source of sulfated polysaccharides. Red marine algae is also high in antioxidants, which help to power up our immune systems to combat free radical damage. It‚s the carrageenans in red marine algae, for instance, that are thought to ramp up interferon production in the immune system. Interferons are proteins dispatched by cells to meet the advance of intruding viruses, inhibiting the ability of said viruses to replicate and cause damage.1 Carrageenans also increase the productivity of T and B-cells which destroy cells already infected with a virus. Because of this, red marine algae is considered by some to be a powerful preventative measure against everything from yeast infections and shingles to serious viruses like HPV and Epstein-Barr.13b Spices: Many spices‚such as clove, oregano, thyme, cinnamon, and cumin‚possess significant antibacterial and antifungal activities against food spoilage bacteria like Bacillus subtilis and Pseudomonas fluorescens, pathogens like Staphylococcus aureus and Vibrio parahaemolyticus, harmful fungi like Aspergillus flavus, and even antibiotic resistant microorganisms such as methicillin resistant Staphylococcus aureus. Therefore, spices have a great potential to be developed as new and safe antimicrobial agents.14
CONCLUSIONMorbidity and mortality are mainly caused by infectious diseases all over the world. The World Health Organization reported that 55 million people died worldwide in 2011, with one-third of the deaths owing to infectious diseases. Antibiotic resistant microorganisms can increase mortality rates because they can survive and recover through their ability to acquire and transmit resistance after exposure to antibiotic drugs, which are one of the therapies to infectious diseases. Antibiotic resistant bacteria threaten antibiotic effectiveness and limit the therapeutic options even for common infections. The decline in research and development of new antibacterial agents, which are able to inhibit antibiotic resistant disease-causing microorganisms such as S. aureus, aggravates the emerging antibiotic resistance. Therefore, much attention should be paid to natural products, which could be used as effective drugs to treat human diseases, with high efficacy against pathogens and negligible side effects.14 We all need help via nutritional assistance by eating an organic, mostly plant-based, colorful diet while supplementing with food-based supplements. A daily approach to immunity is no longer an option. It is a necessity to combat known and unknown pathogens, be they bacterial, viral, fungal, parasitic, or mutagenic in nature. The goal is not the avoidance of these pathogens, as it is not realistic or possible. The goal is to mitigate the damage a pathogen can do while our immune system works on identifying and destroying it. Pathogens have been here for at least as long as we have, on us, and in us. Like inmates housed in an institution, there are actions we can take to prevent them from taking over the asylum. During certain instances, the health of your immune system can literally be the difference between life and death for those who have a weak or compromised immune system. The elderly and those with an underlying health condition most often have fragile immune systems. So do individuals who eat a diet low in immune-boosting nutrients, those who make poor lifestyle choices, and others who are unfortunately genetically predisposed to low immunity.
- Massimo Mangino, Mario Roederer, Margaret H. Beddall, Frank O. Nestle, Tim D. Spector. Innate and adaptive immune traits are differentially affected by genetic and environmental factors. Nature Communications, 2017; 8: 13850 DOI: 10.1038/NCOMMS13850