This book was so good!
An illuminating non fiction book that examines chronic inflammation in the body as a cause of many health problems and explains how our immune system gets confused by our current Western eating habits into being chronically inflammed. Really well explained and an interesting combination between explaining the biology of the immune system and the history of how things were discovered.
The most fascinating part was the explanation of how your gut has an immune response to everything you eat and an anti-inflammatory diet can really help your immune system ward of inflammation (which can then travel in the blood to other organs in your body) and how fibre is acctually benefical for your gut and how certain herbs and spices can transform foods into unleashing their benefical properties.
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Quotes:
“In all organisms, phagocytes-macrophages and microphages — digested foreign matter, actively participating in inflammation. In more complex animals, blood vessels served as conduits through which phagocytes and other white blood cells could rush to embattled areas.”
“We now know that the immune system is divided into two major branches: innate and adaptive. An inflammatory response can involve either branch-or both. The innate immune system is our first defense against foreign threats. Its initial barriers are both physical and chemical, including layered sheaths of skin and body orifices opening into hollow tubes-like the airways, intestines, and genitalia-that are lined with sticky, protective liquids. The innate immune system also includes the hair on our bodies, brows, and nares and even the fine lashes on our eyelids. It defends with bodily secretions such as mucus, bile, and acid. Or spit, sweat, and tears. It is made up of our most ancient immune mechanisms, the ones we share with our primordial ancestors, and it is the main force behind acute inflammation.
Acute inflammation comes and leaves quickly, typically in a few days, fighting intruders while minimizing damage to healthy tissue. Phagocytes, including neutrophils and macrophages, rush to the site of tissue damage, ingesting germs or damaged cells and other foreign materials. Other types of white blood cells, like basophils and eosinophils, may join the fray. The four cardinal signs of inflammation noted by Celsus-redness, heat, swelling, and pain— usually accompany acute inflammation. In injured tissues, blood vessels widen and blood flow surges, causing redness and heat. The walls of inflamed vessels become more porous, allowing inflammatory cells, protein, and fluid to leak into tissues, creating swelling and putting painful pressure on nerve endings. Endothelial cells, which line blood vessels, become injured. Clotting systems are activated, making blood stickier by rushing platelets-small, colorless fragments that congregate in clumps —and other special substances into the area.
The adaptive immune system, which involves defenses that only exist in vertebrates, is more complex and slower to react, but also more targeted. The key players are lymphocytes — small, round white blood cells that can be divided into B cells and T cells.' B cells express antibodies on their cell surfaces that can bind to specific antigens, molecules that are capable of stimulating an immune response, Antigens may be present on all kinds of foreign material, including germs, toxins, food components, tissues from other individuals (like transplanted organs), and even cancer cells. T cells take on various personalities, including "helper" T cells, which assist in activating other immune cells, and "killer" T cells, which focus on removing pathogens.”
“Inflammation, as scientists began to realize over the last decades, is more costly than ever imagined. It is involved not only in a few select disorders but in in the a wide range of ailments that are the most common causes of death in the world today.”
“Cytokines and chemokines, for example, are small protein messengers with big effects. When a germ makes its way into the body, cytokines and chemokines are among the first signals the immune system generates. They determine the quantity and quality of the inflammatory response, communicating with immune organs like the thymus, spleen, and lymph nodes to mobilize even more inflammatory cells into the blood-stream. They can inflame nearby blood vessels and tissues or affect the entire body with a fever or rapid heartbeat.”
Cancer and chronic inflammation
“Balkwill studied tumor necrosis factor alpha (TNF-a), a classic inflammatory cytokine typically produced by macrophages and other immune cells. It was named for its ability to kill cancer cells when injected into tumors at high levels. But Balk-will found that TNF-a could behave differently when it lingered as a low-level force, promoting cancer instead. When she turned off the TNF-a gene in mice, eradicating even low levels of TNF-a activity, the mice did not develop tumors. Anyone working on TNF-a as an anticancer agent was horrified to see that the inflammatory molecule was instead working as a tumor promoter.”
“Dvorik made a seminal discovery in 1983 when he found that cancer cels secreted an abundance of a protein called vascular endothelial growth factor (VEGF). VEGF makes blood vessels more "leaky" (allowing molecules or cells to move in and out of the vessel morg easily) and stimulates angiogenesis, the growth of new blood ves sels. Solid tumors cannot thrive without an adequate blood supple.
Angiogenesis helps cancers grow as it does human embryos, allowing cells to obtain reams of nutrients and oxygen to support their wild expansion. Dvorak's findings, along with those of other scien-tists, helped pave the way for anti-angiogenesis treatmeuts to halt or reverse tumor growth.”
“Macrophages, which typically chew up cancer cells as they would a germ, can turn into traitors. These corrupt macrophages, or tumor-associated macro-phages, are found in most malignant tumors. In some cases they comprise up to half the tumor mass… Macrophages help tumors acquire several of the classic hall-marks. They produce immunosuppressive molecules, protecting the tumor from being harmed by the immune system. They secrete growth factors and cytokines, like IL-6 and TNF-a, that promote a tumor's unchecked growth. They produce the angiogenesis-promoting VEGF, allowing tumors to drink from a robust blood supply. Macrophages degrade a tumor's extracellular matrix, its physical scaffolding, just like they swallow dead cells and debris in wounds, paving the way for cancer to spread to distant sites of the body.”
“At least a quarter of all cancers originate from overt, chronic tisPatienis
sue inflammation. In my own specialty, inflammation can spring up anywhere in the digestive tract, from the mouth to the anus. Chronic, uncontrolled inflammation can cause mild to severe gastrointestinal issues and increase cancer risk. Bad heartburn bathes the esophagus, the hollow tube connecting the mouth to the stomach, in acidic fluid.
The ensuing inflammation distorts the cells of the lower esopha-gus, leading to a precancerous condition called Barrett's esophagus.”
Fat cells and inflammation
“But adipose tissue, beyond its known role in metabolism, was pumping out inflammatory cytokines —not just TNF-a, as later studies showed, but many, others as well, like IL-6, IL-1ß, IL-1, and interferon-gamma (IFN-V). It was the beginning of a paradigm shift that connected fat and inflammation.”
“In lean mice and humans, macrophages remained solitary and scattered among the fat cells.
In contrast, macrophages clumped together in the flesh of obese animals, entirely surrounding fat cells in some cases and mimicking the layout of macrophages in chronic inflammatory diseases such as rheumatoid arthritis. Meanwhile, the number of macrophages in the fat of mice and humans grew in direct proportion to the size of fat cells and body mass indices. Their percentage in fat tissue ranged from under 10 percent in lean individuals to 40 percent in the obese and over 50 percent in the markedly obese. And greater numbers of macrophages even sailed through the blood of these markedly obese individuals.
Macrophages respond to stress. But the body has not evolved to manage overeating, which is one of the biggest stresses of modern life. In lean, healthy individuals, existing macrophages in fat tissue help to maintain an anti-inflammatory state through many path-ways, including by secreting anti-inflammatory cytokines. But they alter their behavior in obesity, and an irate immune response ensues.”
“Many hormones in fat tissue, like leptin, have dual roles. Leptin controls food intake and regulates body weight, but it is also an inflammatory molecule. In obesity, as the body becomes resistant to leptin, fat cells secrete more and more of it, promoting hunger and inflammation.”
Ageing and chronic inflammation
“But a third option exists: some damaged cells simply surrender to time. No longer able to carry out their duties, they stop growing and dividing yet remain alive, entering a retirement phase kaown as senescence. Senescent cells initially secrete substances that hep to repair damaged tissue. But over time, as their numbers increase they disrupt the structures of organs and tissues. Senescence is not flip of the switch but rather a gradual evolution, from a transient, reversible quality to a chronic, immutable one. And senescent cells, having divested themselves of their traditional responsibilities, are far from idle. They become potent inflammatory agents, churning out cytokines like IL-6 and IL-1ß, altering the behaviors of normal cells nearby and those all around the body, including immune cells.”
“Microglia, the most numerous cells in our brains aside from neurons, are central to the link between inflammation and neu-rodegeneration. Like macrophages elsewhere in the body, they engage in tissue repair and attempt to protect the brain from infections, toxins, or anything else that can damage neurons.
The crystal-like amyloid plaques that characterize Alzheimer's, with surface molecules reminiscent of some bacteria, are foreigners that elicit an innate immune response honed over millen-nia. Microglia attempt to eat and digest amyloid, much like their counterparts stuff themselves with cholesterol in atherosclerotic plaques. They release loads of cytokines in the process, like TNF-a, IL-1B, and IL-6, activating other microglia. This process, typically fleeting, becomes ongoing in Alzheimer's disease, where microglia are high-strung and hyperactive. The ensuing chronic inflammation maims neurons, feeding dementia. When nerve cells become inflamed, the connections between them are less adept at learning and storing information. Inflammation may also fuel the growth of plaques and tangles directly or by hindering the ability of microglia to clear them.”
Inflammation and Mental Health
“Microglia activated by body inflammation run amok, producing inflammatory cytokines that destroy neural connections in the brain that affect mood and behav-lor. Brain inflammation reduces the amount of serotonin flowing between neurons. Cell studies suggest that inflammation may also increase the risk of depression by suppressing the birth of new brain cells and quickening the death of existing ones.”
Intestines and Inflammation (Chapter 6 was my favourite)
“Much of the immune system lives in the gut, which is heav ily exposed to the external world. There are three major channels through which inflammatory triggers enter our system: the skin, the lungs, and — an especially susceptible point of entry —the gastrointestinal tract.”
“The food we eat can directly spark or inhibit an inflammatory response by the immune system. Innate immune cells-including macrophages, neutrophils, and dendritic cells-and the epithelial cells lining the intestines rely on primordial pattern recognition receptors to closely examine germs and other matter. These receptors, which are embedded in cell membranes, recognize alien material and trigger a powerful inflammatory or anti-inflammatory response, activating genes and generating a cascade of signals conserved across the phylogenetic ladder, from insects to plants to humans. They can even respond to distress signals spewed out by stressed cells all over the body. In short, the immune system is prepared to fight food as it would a germ.”
“One critical method by which the conversations between. microbes and immune cells help prevent disease is by training our bodies to distinguish harmless food and germs from their toxic coun terparts. A great deal of this dialogue takes place within the intes-tines. The intestines contain the largest reservoir of macrophages in the body. Their lives are often hard and brief, constantly yielding to younger replacements circulating in the blood. Not only do they heal wounds and fight germs, as in other tissues, but they also learn to live alongside a multitude of gut microbes, functioning within complex layers of the intestinal immune system.
At the inner lining of the intestines, the interface between "self" and the exterior world, rectangular epithelial cells shove tightly against each other like bricks, limiting the entry of harmful sub-stances. These cells soak up nutrients and secrete a protective layer of slippery, watery mucus that coats the digestive system and contains an antibody called immunoglobulin A (IgA), which bars the entry of toxins and bad germs. The mucosal immune system exists not only in the intestines but also in other body cavities exposed to the environment, including the nares, lungs, eyes, mouth, and geni-talia. Burrow deeper into the wall of the intestines and the immune system's vernacular bares a cohesiveness that unites historically fractured segments of immunology. Beyond the fence of epithelial cells lies the lamina propria, loosely packed tissue that holds most intestinal immune cells, the blood supply, and lymph vessels. Here, innate and adaptive immune cells, including macrophages, dendritic cells, and B and T lymphocytes, mingle. Within the lamina propria sits the gut-associated lymphoid tissue, the largest lymphatic organ in the body, consisting of special patches of lymphoid tissue found throughout the intestines and lymph nodes all over the abdominal cavity. Teeming immune cella in these areas stand ready to ignite an inflammatory attack against adverseries.”
“In creating this fine balance, the gut errs towards tolerance, dampening its immune responses, a characteristic that evolved to prevent needless immune activation and inflammation against benign substances. Intestinal macro-phages, the gatekeepers of tranquility in the gut, are distinct from macrophages in other parts of the body. Healthy intestinal macrophages are trained to tolerate, so their ability to recognize microbial structures and to induce an inflammatory response is muted.
They remain patient when provoked by microbes and often shy away from making inflammatory cytokines, although they are still able to engulf, swallow, and kill when needed. But sometimes the response can go awry, with genes and the environment colluding to disrupt a yin-yang state, creating food allergies, celiac disease, inflammatory bowel disease, or other problems.”
“A complex picture of the immune system began to manifest.
The presence of an animal's genetic code does not in itself suffice to create a mature, healthy immune system. Microbes must assist in this nuanced task, as revealed by the isolated anguish of germ-free mice.”