Editor's Note
The number of infections with the new crown Omicron strain has risen, attracting the attention of a wide range of readers. As a professional science popularization number for aging research, it has been noted that many aging and new crown are inextricably linked, in fact, many studies have proved that new crown is an "aging-related disease". On the one hand, many anti-aging molecules can alleviate symptoms and assist in treatment; on the other hand, telomere shortening leads to an increase in the number of new coronavirus receptors in the human body and an increase in the risk of infection.
Whether it is various vaccines, Pfizer's Paxlovid, or Lianhua Qing plague and other treatment measures, from the mechanism point of view, it is to suppress the replication of the virus and improve the body's ability, but in the end, the virus is completely eliminated or autoimmunity. However, the immunity is strong and weak, and with the weakening of age, anti-aging can enhance immunity, and naturally can also fight against the new crown.
In this way, from the perspective of immunity, we urgently and deeply sorted out the operation mechanism of the immune system, the causes of low immunity, and summarized practical health advice, hoping to help everyone fight the virus.
Illustration: Synopsis (too long to see the condensed version)
Enhancing Immunity and Immune Response section in Part III;
There is a tutorial on the calorie limit calculator at the end of the article;
The document form, audio, and video learning methods of this article are also mentioned at the end of this article.
1. Introduce the process of various pathogens, including the new crown virus, which are normally destroyed by the body's immune system;
2. Analyze the reasons for the gap in immunity between people, including genetic factors, aging of the immune system caused by increasing age, bad living habits, excessive stress, pregnancy, disease, etc.;
3. Provide a series of practical strategies to improve immune system function, including dietary nutrition, maintenance of basic exercise, smoking cessation, decompression, calorie restriction, immune enhancement supplements and other daily interventions, and introduce medical measures such as hormone therapy, immune-enhancing drugs, vaccines and other medical measures (summarized in the figure below)
Figure note: Immune enhancement strategies mentioned in this article (temporalist arrangement)
The article is long, and if you want to go straight to the topic, you can swipe to the recommendations section to enhance resistance and immune response. This article is universal and practical, and you are welcome to share it with your relatives and friends for reference.
Why is it said that viral infections are ultimately defeated by the immune system?
Note: Outline of this part
1. Introduction to the immune system
The immune system is a system composed of immune organs, immune cells, and immune molecules (secretions of immune organs and cells), which mainly play a role in defending against foreign viral and bacterial infections and eliminating aging/diseased/dead cells.
According to function, the immune system's defense or immune response to pathogen occurrence can be divided into two types: innate immunity and adaptive immunity, which are different in composition, as detailed in the following figure:
Figure note: Composition of the immune system - innate immunity
Figure note: Composition of the immune system - adaptive immunity
When healthy cells are infected with the virus, intermediates that replicate viral genetic material (such as double-stranded RNA intermediates for the new coronavirus) activate the host's intracellular defenses and induce the host to synthesize interferons. Interferon on the one hand inhibits the proliferation of the virus, on the other hand, it releases warning signals to the immune system, usually the virus first activates the innate immune system, then activates the adaptive immune system, and finally kills the virus and removes the infected diseased cells, which can be cured.
2. The process by which the immune system kills the virus
(1) 3-5 days after infection, innate immunity is dominant
The first 3-5 days of infection with the virus are a battleground for natural killer cells (NK cells), macrophages, dendritic cells, and neutrophils in the innate immune system:
The surface of the virus-infected cells will express a signal of infection, which makes them detected by patrolling natural killer cell (NK) cells, which are subsequently induced by NK cells for apoptosis.
As hard as NK cells work to clear the virus, there are macrophages, dendritic cells, and neutrophils. The first 2 are responsible for eating the virus particles between the cells and displaying the virus fragments on their surface; the neutrophils are "suicide attacks", and after eating the virus, they also die and become what we call "pus".
The above immune cells occur within 3-5 days of the body's infection, which curbs the replication and spread of the virus to a certain extent, but there is always a part of the new crown virus that will break into the next line of defense: the adaptive immune system.
The process by which macrophages and dendritic cells exhibit viral debris (forming the MHC-antigen complex) is called "antigen presentation," and these two types of cells, also known as antigen-presenting cells (APCs), are necessary to activate the adaptive immune response.
Note: How APC labels antigens
(2) In the late stage of anti-infection, innate immunity + adaptive immunity
The protagonists of adaptive immunity are T lymphocytes and B lymphocytes, which usually reside in lymph nodes. Macrophages and dendritic cells that have engulfed the virus migrate to the lymph to find T lymphocytes, which are stimulated to activate, rapidly clone and proliferate and differentiate into helper T cells (Th), regulatory T cells (Treg), and killer T cells (Tc), thus activating the ultimate and more powerful path of killing:
Th cells activate B lymphocytes, promote their clonal proliferation, and release antibodies in large quantities (up to 2000 antibodies/sec for several days); antibodies tightly envelop free viral particles between cells, directly neutralizing their toxicity;
Tc cells can not attack free viruses, but attack cells infected by viruses, it recognizes infected cells through its own surface receptors (TCR), releases perforin, granulase, and breaks the cell structure, genetic material, in addition to infected cells, cancer cells are also its killing objects;
After the disease is controlled, most of the T cells and B cells involved in the battle undergo apoptosis through the Fas-FasL pathway, and those who survive become memory lymphocytes that have a memory of the virus, and when the same virus invades again, they immediately activate and proliferate and respond quickly;
Treg cells are the sweepers of the immune response, responsible for suppressing the immune effect after the condition improves, preventing them from overmagnifying the body itself, and play an important role in maintaining the balance of immunity.
Note: Summary of the adaptive immune response process
The essence of various medical measures to combat new crown pneumonia is to strengthen the patient's autoimmune response with external forces and exacerbate the above-mentioned anti-virus reaction, but the "executor" of anti-virus must also count the immune system itself. People with immune aging or immunodeficiency may have more severe symptoms, slower recovery, and more sequelae.
Enhancing Immunity and Immune Response section in Part III;
There is a tutorial on the calorie limit calculator at the end of the article;
The document form, audio, and video learning methods of this article are also mentioned at the end of this article.
Second, the cause of low immune function
Some people can keep their nucleic acid negative in the case of the new crown infection of their roommates, and some people have healed themselves when they are unaware of the virus after infection; in contrast, some people are fully armed "passing through the yang road" and are still recruited, vomiting and diarrhea after infection with the new crown, and being plagued by sequelae for a long time after treatment... Why is the immunity gap between people so large? Genetic factors, immune aging, and life factors may explain such phenomena.
Note: Outline of this part
1. Genes cause individual immunity to be uneven
First, because human ancestors lived in different regions, and cross-regional trade was not as smooth as it is now, there was relatively little exchange between different races. Therefore, due to the cumulative influence of regional materials, climate, geographical environment and other factors, there are some differences in the working mode of the immune system between different races today.
According to archaeology, human ancestors came to China from the African continent 80,000-120,000 years ago, migrated from Africa to Europe about 40,000-60,000 years ago, and in the process of adapting to the New World, the immune systems of these migrating descendants evolved. For example, a study by the University of Montreal found that African-American macrophages kill three times faster than Europeans, and 30% of the 12,000 genes of the two are different before they are infected by bacteria, and the direction and degree of change in the immune response are far from each other.
Immune function varies between individuals of the same race. A large-scale study found that for the same influenza A virus, some people were asymptomatic after infection, some people were severely symptomatic, and the gene expression patterns of the two types of people in the immune response were very different (see figure below), indicating that the "working habits" of the immune system differed between people.
Due to genetic influences, everyone's immune system is not exactly the same, and people who are born "weak and sick" are indeed disadvantaged in the face of the new crown. In addition, there are some factors that can also lead to a decline in human immunity.
2. Immune aging: earlier than the first hundred hairs
Picture note: The immune system (red line) goes downhill from around 20 years old (from dxline.info)
The immune system has two important organs: the thymus gland and the bone marrow, which are the birthplace of immune cells and affect the overall number and functional integrity of immune cells. However, they age earlier than we think.
(1) Thymus atrophy
The thymus gland is the place where T cells mature, and thymus senescence mainly affects the number and composition of T cells. The development space of T cells in the thymus is called the thymus epithelial space, where lymphoid precursor cells differentiate into naïve T cells (Na ve T cells), and eventually develop into helper T cells and killer T cells according to demand.
Human thymus function from adulthood began to degenerate, thymic epithelial space will increase with age year by year, to 70 years old, thymic epithelial space is only 1/1 of the maximum time, the volume of the entire thymus gland is also "shrunk" a lot, as shown in the following figure:
Note: Thymus degeneration occurs when we are young
Thymus atrophy will lead to a decrease in T cell regeneration, and the quality and function will change, and the proportion of various T cell subtypes will also change. Scientists believe that the decrease in T cells and the change in the proportion of subtypes are the main causes of immune aging. Because T cells are the strongest and most excellent immune cells, they are the elite teachers of anti-virus and anti-cancer.
Why does the thymus "abandon" us before we reach the so-called "age of old age"?
There is currently no uniform answer internationally, but many of the answers tend to be evolutionary antagonistic pleiotropy. We can understand that nature's focus is on when we were young, not when we were old. In nature's view, the biggest hurdle we need to overcome is the risk of prenatal stillbirth, and the risk of neonatal infection and death after birth. Our ancestors did not live to be gray-haired, so nature's judgment of these 2 "biggest difficulties" is objective. Once you have passed these 2 levels, when you grow up and face the danger of hunting or farming, you have a mature body and strong physical strength, and nature "does not have to worry about it", so the thymus gland that is born with full work is always accompanied by the growth and expansion of our other organs, and it is going to wither in the opposite direction.
(2) Hematopoietic stem cell senescence
The "mother of immune cells" hematopoietic stem cells in the bone marrow belong to adult stem cells, have no telomerase activity, and cannot maintain their own telomere length, so they must withstand replication aging (RS) after a certain number of replications. In addition, studies have shown that stress and stress can also promote bone marrow hematopoietic stem cell aging, such as accumulated oxygen radicals (ROS) can cause DNA damage, environmental factors (neuro-endocrine bone marrow microenvironment) can make young bone marrow hematopoietic stem cells aging faster.
Note: Bone marrow hematopoietic stem cells are the "mothers" of various immune cells
The aging of bone marrow (hematopoietic stem cells) will greatly reduce the production of "raw materials" of immune cells, and the final result is that the overall reduction of immune cells, the proportion of mast cells and dendritic cells associated with inflammatory reactions increases, and the proportion of B lymphocytes and T lymphocytes with the ability to kill viruses decreases.
This explains why the elderly are prone to acute and chronic inflammation, but at the same time have low immunity: the number of pro-inflammatory immune cells increases, and the immune effector cells that perform anti-disease functions become fewer.
3. Constant stress
Which part of your body do you think is dealing with your stress?
The answer is the immune system.
The immune system is originally used to fight infection, monitor cancer and aging, but in the stress state, cortisol, norepinephrine, epinephrine and other hormones activate hormone receptors on the surface of immune cells, mobilize immune cells, and prepare them for response. Long-term, reciprocating stress stimulation is a drain on the precise and expensive immune system, such as the sleep deprivation phenomenon we mentioned in the chronic inflammation article, which repeatedly stimulates the immune response, ultimately leading to an increased risk of autoimmune disease.
In addition, negative emotions are also harmful to immunity. Human studies have found that depressed patients have overall leukocytosis, mild decrease in NK cells, decreased T cells, and both have decreased function; neutrophils are increased, but phagocytic function is decreased. Widows have reduced T cell responsiveness, T and B lymphocyte proliferation is inhibited (especially in February), NK cell lethality is reduced, and plasma cortisol hormone concentrations, which symbolize stress, increase.
4. These people are also immunocompromised
After weaning, infants and young children, due to the immune support of breast milk, need to train the immune system through countless times of illness recovery in order to form a truly their own immune barrier.
Pregnant women are also at a time of low immunity in their lives due to fluctuating hormone levels and the need to deliver large amounts of nutrients to the fetus.
People who are sedentary, obese (especially abdominal obesity), and have a variety of chronic diseases have serious chronic inflammation in the body, which will also deplete resistance and immune response.
In the current global environment where the new crown virus strain continues to mutate and the time for the virus to truly become extinct is still unpredictable, we need to fight a protracted health defense war. Since the cure of viral infection relies on immunity, if we can start from the factors that affect immune organs and immune cells, we may be more reliable than expecting new and side-effect-free drugs.
III. Recommendations for Enhancing Resistance and Immune Response
The immune system is stable and efficient, affected by multiple factors, but for all groups, diet, exercise, smoking cessation, and decompression are the "golden oil" that restores immune health. Pay attention to these aspects, and the personal "fight against the epidemic" is half successful.
Note: Outline of this part
1. Diet
Dietary nutrition is important for maintaining immune balance, and as a result, the incidence of infectious diseases is higher in famine countries. People who are picky eaters, over-diet, and have poor absorption and metabolism are often immune to vitamin deficiencies and protein deficiencies.
The nutritional status available to cells is a key factor in determining the intensity, efficiency, and outcome of the immune response. Protein deficiency as a key source of nutrients is associated with impaired anti-virus processes such as lymphocytes killing viruses, phagocyte engulfing and presenting pathogens, complement activation, antibody synthesis and secretion. Therefore, during the epidemic period, meat (including seafood, river fresh), eggs and milk should be eaten as much as possible to ensure protein intake to maintain the normal operation of the immune system.
The recommended daily average protein intake in the United States is about 0.8g, but this is the most basic intake to prevent malnutrition, and does not include complex work-life affairs, anti-epidemic stress, and additional consumption of protein by sports and fitness. For people of different ages and different physiques, the recommended daily protein intake is different, and the summary is as follows, which is used as a dietary reference during the epidemic period (reference source: EXAMIN).
In addition to protein, macronutrients such as vitamins and minerals also support immune functioning.
Families with abundant fruits and vegetables can supplement dietary fiber, vitamins, and minerals through fruits and vegetables, because B, vitamin C, vitamin D, zinc and other elements are closely related to immune system function. For example, in the depths of the epidemic blockade management area, take out the multivitamin complex tablets with ash, or turn to the pharmacy to ensure the supply to buy multi-dimensional tablets, which can make up for the lack of vitamins caused by the shortage of materials and insufficient food types to a certain extent, and help maintain resistance and immune response.
2. Exercise
Ancestors hunted and collected every day, evolved an immune system that matched exercise, and the "temptation to lie flat" after school and after work seemed to make us forget that "exercise is a necessary condition for the immune system to work well."
(1) Guidelines for fortified immune fitness for young people
Adults should do at least 150-300 minutes of moderate-intensity aerobic exercise per week, or 75-150 minutes of high-intensity aerobic exercise.
Common aerobic exercise includes: brisk walking, running, swimming, playing ball, cycling... So how to judge the intensity of exercise?
"Moderate intensity" means that you can no longer sing a song while exercising; "high intensity" means that you can no longer say sentences while exercising. Everyone's physical conditions and athletic ability are different, without deliberately pursuing heart rate or type of exercise, according to the above methods, you can basically judge the "medium intensity" and "high intensity" that are considered by their own body.
People in North America love fitness very much, and the American Exercise Guide 2018 recommends on the basis of aerobic exercise: strength training involving each major muscle group should be performed 2 or more days a week, which will lead to more improvements in aging indicators (including immune indicators) than aerobic exercise.
Illustration: The main muscle groups of the human body (Calisthenicmovement)
(2) Recommendations for intensive immunization campaigns for the elderly
For the elderly who are prone to aging, a safer form of exercise can be opted for - balance training. Improving muscle strength and limb stability through balance training can help the elderly prevent falls, and the most popular balance training is the long-established tai chi from the mainland. For the elderly with limited physical activity ability and obvious weakness, grasp the principle of "starting low, slow progress", balance training at the same time, supplemented by some flexibility training such as muscle stretching, and then further challenge light weight strength training to improve physical fitness.
It is well known that exercise helps maintain the ability of the thymus, T lymphocytes, and NK cells to enhance resistance and virus killing in terms of the immune system. It should be noted that high-intensity exercise should be carried out intermittently, and the duration and total duration of a single time should not be too long - the body's recovery will damage the function of lymphocytes, NK cells, and neutrophils, and blunt the immune system. Be sure to sleep enough that night after exercise to help the exercise tissues and organs repair themselves.
In addition to deliberately carrying out a certain intensity of outdoor or home physical exercise, working from home in the epidemic area, especially computer workers, should also get up every half hour for simple activities, such as pouring water, stepping in place, and stretching shoulders and arms, which can prevent the rise of chronic pro-aging inflammation caused by sitting for a long time, and reduce the risk of cardiovascular disease and all-cause death.
3. Quit smoking
Cigarettes are immune system killers, not only destroying the respiratory mucosa and making them more susceptible to infection with viruses, but also inhibiting the body's immune response to pathogens, interfering with immune recognition, and aggravating autoimmune diseases. There are more than 7,000 chemicals in tobacco, which have complex effects on macrophages, NK cells, dendritic cells, T lymphocytes, B lymphocytes (pictured), the U.S. Centers for Disease Control and Prevention (CDC) has written: Cigarettes may make your immunity weaker when fighting viruses and stronger when attacking yourself.
4. Unzip
Regular sleep and a cheerful mood help the immune system to work at its best possible. The meditation reported several times by the Time School is a means to not only relieve stress and improve immune aging, but also to protect telomeres and promote health and longevity, and the well-known athlete Gu Ailing is also a loyal enthusiast.
During the epidemic, major sports apps and fitness communities have launched home practice courses, many of which have meditation and practice, which everyone can operate.
5. Calorie restriction
Calorie restriction (CR, which refers to the reduction of dietary calories by 10-50% per day) has been around for more than 80 years and has been shown by various studies to benefit animal health and even extend the lifespan of many species, it promotes the production of new T cells in the thymus gland and prevents the accumulation of old T cells. CR also reduces the body's nutritional perception and metabolic burden, and has a good control effect on the chronic inflammation of overweight, obesity, and "three highs" mentioned above, and the chronic inflammation is alleviated, and the pace of immune aging is naturally slowed down.
Figure Note: Results of some studies on calorie restriction in healthy people
The trouble with CR is that it requires daily calculation of total calories in food, and long-term adherence (months or even years) to have obvious and solid results. During the CR period, special attention needs to be paid to avoiding malnutrition, especially in the diet section, we also mentioned that amino acids are the most powerful fuel for the immune system, and CR pursues to eat "less and fine", rather than "less and sloppy".
Specific to the number of calories, first of all, you can search for the Internet "TDEE Calculator" to calculate the total daily energy expenditure (remember to enter the fitness frequency and daily work nature), according to about 80% of the TDEE calories to plan dietary calories, you can play a mild calorie restriction effect.
Friends who can't operate, you can find the time assistant (any of the staff with "time pie" in the WeChat friends list) to get the TDEE calculator, calculation tutorial, and can also refer to the average TDEE of different ages shown in the figure below.
Figure note: TDEE of people who have a daily habit of light exercise (such as jogging, brisk walking).
It should be noted that CR can either reduce dietary calories by 20% for mild restriction, or it can be harsh to reduce dietary calories by 50%, and in some model animals, strict CR has a very significant effect. However, people have complex social attributes, work, exercise, labor, emotions, energy have a certain consumption, such as the intention to adhere to CR, daily dietary calories we recommend not less than the basal metabolic value (BMR), otherwise it may lead to emotional overeating, obesity, rapid loss of muscle mass and other issues, affecting the quality of life and physical health.
Figure note: BMR calculation formula
6. Supplements for maintaining healthy immunity
For now, we recommend stockpiling and consuming immune support supplements.
A number of plant extracts have been shown to enhance the patrolling and disinfecting functions of immune cells, including mushroom extracts, immune-boosting probiotics, β-dextran, fucoidan, fucoidan, garlic, echinacea, licorice root extract, astragalus extract, curcumin, ginseng extract, elderberry, and more.
7. Hormone therapy
Hormones such as thyroxine, growth hormone, dehydroepiandrosterone (DHEA), and sex hormones (such as testosterone) may enhance the immune response of the elderly and delay the aging of the immune system. But no matter how the hormone should be used with caution, such as growth hormone, its effect molecule IGF-1 has long been found and the overall life expectancy is negatively correlated, many IGF-1 missing dwarfism patients, look younger than their peers, and even "look like a lifetime will not be old." Exogenously given sex hormones may cause endocrine imbalances, which can cause health risks in the breast, testicles and other parts, and we do not encourage the public to use as daily health care therapy.
8. Immune enhancing agents
For people with particularly low immunity, especially those with identified and immune-affecting diseases, clinical interventions can be used to artificially stimulate the body's immune response (only for introduction, please follow the doctor's advice):
Immunomodulators IL-2, IFN-γ, IL-12, which have the effect of promoting the activation, proliferation and differentiation of immune cells;
Indomethacin enhances the ability of macrophages and dendritic cells to present viruses and activate T\B lymphocytes by blocking PGE2 (prostaglandin E2);
Dimercaptoethanol significantly improves the insufficiency of thiol (-SH groups, required for protein synthesis) in senescent cells, which is conducive to improving protein synthesis in the body and delaying immune aging;
Thymus peptide is a hormone secreted by the thymus gland, which participates in T cell differentiation and enhances the function of T cells and NK cells, and supplementation with thymus peptide can play a role in temporarily strengthening the immune response;
Interferon is an alarm after cell infection, and also has the effect of inhibiting viral proliferation and stimulating immune cell function;
9. Vaccines
Vaccines are the greatest inventions, without which humans would probably perish from an infectious disease.
The principle of the vaccine is to inject antigens that cannot proliferate (such as virus shells without genetic material) into the human body, wait for the body to recognize and respond to it, and after the completion of the immune response, the body stores a large number of memory lymphocytes, and the next time it encounters a similar virus, the body can make a faster and stronger response. This is also the reason why people who have completed all vaccinations in the COVID-19 outbreak have mild symptoms after infection.
In view of the current anti-epidemic situation, we also recommend that readers who do not have injections of booster needles inject boosters as soon as possible, especially the elderly at home, or those who are immunocompromised due to illness.
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Between the time school readers are eager to pay attention to the sequelae of the new crown virus and whether it has an impact on the aging of the body after recovery. We have collected several people who have recovered from COVID-19 for interviews from the Time School readers, and will follow up in the next week. In addition, we will conduct live discussions on how to strengthen the immune system and COVID-19-related issues in the future (and we will also seek to connect with the recovered to share).
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