Apr
24
2022

Immune System Responses against Covid-19 or anti-Covid Vaccination

This article is about immune responses against Covid-19 or anti-Covid vaccination.

Investigations of the immune system showed that people who had Covid-19 and subsequently were vaccinated had an immune response that lasted for at least one year. In the following a discussion follows about the details why this is so.

The WHO confirmed more than 430 million cases of Covid-19 since the pandemic started. 4.9 billion people or 63.9% of the world population received at least one vaccination as of late February 2022.

How vaccination against Covid-19 works

The vaccine attacks the spike protein of the Covid-19 virus (SARS-CoV-2). The body produces antibodies through B cell activation. These are lymphocytes that originated from the bone marrow (hence B cells). They are capable of producing large amounts of antibodies that target the spike protein of the virus. It takes at least two vaccinations with the Pfizer vaccine to get a good antibody response. A booster vaccine brings the antibody titer even higher.

Cell-mediated response by killer T cells

When the virus enters a cell, the antibodies are no longer effective. Here the T killer cell comes into play. T killer cells are lymphocytes that were thymus processed (hence the name T cells) and activated by the vaccine. T killer cells function as a second line of defence. These immune cells specialize in detecting virus-infected cells. They immediately destroy these cells before the virus has a chance to replicate and shed more virus copies into the blood stream. It is the T cell response that prevents hospitalizations and deaths. Media coverage misled the public to believe that the bulk of the immune response would be from antibody production. However, the truth is that the T cell response is what is responsible for recognizing Covid-19 variants and why people survive Covid-19 with very little complications.

Long term immunity

When people had a Covid-19 infection the activated B cells that produced antibodies and the T killer cells get converted into memory cells. With a re-infection the memory cells can reactivate themselves to turn again into active B cells producing antibodies and T killer cells. The key for immunity with multiple vaccinations is also the memory cell pool. Those with two Pfizer vaccinations and a booster vaccine are much more immune to Covid-19 than those who only received one or two vaccinations.

Waning immunity

Following an infection with Covid-19 the immunity comes to a peak at 3 months after the start of the infection. The CDC said that people who are 90 days post-infection do not require a quarantine when they meet someone with an active Covid infection. By about 6 months immunity is declining. This is also true for people after double vaccination and a booster vaccine.

Hybrid immunity

The immune response after either a natural infection with Covid or following vaccinations with anti-Covid vaccines lasts only about 6 months. On the other hand, scientists observed that people recovering from Covid infections who subsequently received an anti-Covid vaccine just once had a very strong immune response that lasts for over a year. This is called hybrid immunity. This type of immune response triggers a very strong antibody response that is lasting longer. Immunologists are now researching whether the hybrid immunity is achievable with an improvement to vaccines. Results of this will not be available for several years.

Immune System Responses against Covid-19 or anti-Covid Vaccination

Immune System Responses against Covid-19 or anti-Covid Vaccination

Conclusion

The immune response to Covid lasts for about 6 months; the same is true for the immune response after a vaccination. But when a person comes down with Covid and he or she receives a vaccination one month later, the immune response lasts for over one year. Scientists call this hybrid immunity. At this point experts recommend to have a booster vaccine every 6 months. But immunologists are researching for ways to incorporate the mechanisms of hybrid immunity into vaccines, which likely will not be available for several years.

Avoid deliberate exposure to Covid-19

Some persons who read about the response after a Covid infection and a vaccination misinterpreted this. They took this as an “invitation” to expose themselves to the virus in the hope to boost their immunity. However, a Covid infection remains an illness with potentially serious consequences. There is no way to predict whether the course of an infection will be mild or extremely severe. In addition, a significant number of patients come down with “long covid” and struggle with breathing problems, lack of energy and more. Covid is still here, and our best protection remains the full vaccination including boosters and hygienic measures. This involves masks, frequent handwashing and disinfection of surfaces in daily life.

Jan
22
2022

Booster Vaccinations Against Covid-19 Variants are Very Effective

This article will inform you that booster vaccinations against Covid-19 variants are very effective. Studies in patients from Israel who received a third vaccination (booster shot) showed much less omicron infections. Researchers compared the number of omicron infections in patients with only two shots and another group with three vaccinations (regular vaccination+booster shot). In patients who had booster shots infection rates were 10-fold lower.

Antibody titers matter

What seems to be happening is that antibody titers against Covid-19 rise after each vaccination providing more and more protection against the virus. Patients in this study had 90% less Covid-19 infections after a booster (=3 shots with the Pfizer vaccine) when compared to a double vaccinated group. Researchers compared nursing home residents who were previously sick with Covid-19 versus those who were not. They did PCR tests in April or June of 2020 to identify that there was a past history of Covid-19 infection with a subsequent recovery. Within 3 weeks after one dosage of an anti Covid-19 vaccine their antibody tests rose to above 40,000 arbitrary units (AU) per milliliter. The threshold was 50 AU to be positive.

The Israeli experience

An Israeli study was published on Nov. 5, 2021. Researcher determined the antibody titers in blood samples after anti-Covid-19 vaccinations. They investigated the antibody titers after two vaccinations and compared them to antibody titers after three vaccinations. The latter vaccination is often referred to as a booster shot. 97 study participants had blood tests taken after two vaccinations with an average antibody titer of 440 AU/mL. Any value above 50 was considered to be seropositive. However, 10 to 19 days following the booster shot the average antibody titer rose to 25,468 AU/mL, which is an enormous increase.

Older age patients and kidney transplant patients responding to booster shots

After two vaccinations there were lower antibody titers in older patients aged 67-74 compared to patients age 18-55. But after the booster shot this age difference was no longer present. On the sideline the researcher also followed a group of kidney transplant patients. These would be considered to be patients with a chronic disease. Initially, following the standard two vaccinations these patients were negative for an antibody response. But after the third vaccination (booster shot) 49% of the kidney transplant patients showed a positive antibody test.

Antibody titers in patients with past natural Covid-19 infection

Researchers also investigated the antibody response of patients against the spike protein of Covid-19. As this publication shows after a natural Covid-19 infection plus one vaccination of the Pfizer/Moderna vaccine the antibody titer was 20,120 arbitrary units per milliliter. In contrast, the other group consisted of two vaccinations of the Pfizer/Moderna vaccine. They had antibody titers of 22,639 arbitrary units per milliliter. This was not significantly different from the first group. It also did not matter whether in the first group the prior natural Covid-19 infection was 1, 2, 3 or more months before the first vaccination with the Pfizer vaccine.

Discussion

New information emerged since the beginning of the Covd-19 pandemic. There was confusion about how often people would need a vaccination before they would be immune against Covid-19. After one vaccination with the Pfizer/Moderna vaccine the protection rate against Covid-19 is around 50%. After two vaccinations the protection rate is around 95%. Experience with the booster vaccination teaches us that the protection rate is almost 100%. There was no difference between the antibody response of the group with the age of 18-55 and the group with the age of 67-74 after the third shot (booster shot).

But there is a proviso: the immune system must be capable of full activation to produce enough antibodies by the B cells. B cells are the lymphocytes that traveled through  the bone marrow after which they started producing antibodies against viruses. As the results with the kidney transplant patients showed, only 49% of them were able to produce positive antibody titers. The reason for this is that kidney transplant patients must take immune system suppressing drugs to avoid a rejection of the kidney transplant.

Other reason for poor antibody response

Other patients with chronic diseases (diabetics, autoimmune disease patients etc.) and patients older than 60 can also have a weaker immune system. Part of this can be when one or more of the 14 supplements is missing that are necessary for a full immune response. It is important before the Covid-19 vaccinations to take the 14 necessary supplements to get a good antibody response.

Booster Vaccinations Against Covid-19 Variants are Very Effective

Booster Vaccinations Against Covid-19 Variants are Very Effective

Conclusion

Several studies showed that the antibody response after the anti-Covid-19 vaccine increases significantly. The measurements revealed that after two injections the antibody titer was 440 AU/mL. After the third (booster) injection the antibody titer increased significantly to 25,468 AU/mL. This explains why some people after one or two vaccinations still may be able to come down with Covid-19, but after the additional booster injection (3rd vaccination) the immune response in terms of antibody production is 58-fold higher than after the second vaccination. This gives the immune system a full response. Some patients with chronic diseases (obesity, diabetes, autoimmune diseases etc.) will have certain immune deficiencies. This explains a higher infection rate among these people as well as a higher mortality rate. We all can take the booster vaccine against Covid-19. In addition, we can take the 14 immune supplements to stimulate our immune system.

Dec
25
2021

Drugs that May be Useful in the Treatment of Covid-19

This article deals with drugs that may be useful in the treatment of Covid-19. There are several drugs that may be useful in the treatment of Covid-19. Lately an antidepressant like Luvox has been in the limelight. But antiviral drugs like ritonavir from Pfizer and remdesivir from Gilead Sciences also reduced the number of hospitalized patients with Covid-19. Finally, Merck introduced molnupiravir, an antiviral drug against Covid-19. The health authorities in Great Britain recently approved this drug for use in Covid-19 patients in Great Britain. Apart from drugs, vitamin D3 is still an important factor in preventing and treating Covid-19 as I will mention below.

Luvox for better survival from Covid-19

The Lancet published a study on January 2022 about the effect of Luvox on patients with Covid-19 symptoms. 741 patients received the antidepressant Luvox, 756 received placebo pills. In the Luvox group patients received 100 mg of Luvox twice per day for 10 days. From the Luvox treated patients only 11% had to go to tertiary care for treatment. In contrast, from the placebo group 16% had to go to tertiary care. There were 17 deaths in the Luvox group and 25 deaths in the placebo group. The Luvox group definitely showed a positive effect, although the results were not outstanding. In the following I am discussing other drugs that may be useful in the treatment of Covid-19.

Antiviral agent Remdesivir Improving survival from Covid-19

Here is a run-down of the survival statistics with remdesivir. This drug is manufactured by Gilead Sciences in cooperation with Pfizer. 541 patients received a loading dose of 200 mg on day 1. Subsequently they received 100 mg daily for another 9 days. 521 received placebo pills. The median recovery time in patients with remdesivir was 10 days. Those on placebo pills recovered only after 15 days. The mortality rates were 6.7% with remdesivir and 11.9% for the placebo group on day 15. There was a mortality of 11.4% with remdesivir and mortality of 15.2% with placebo pills on day 29. Although the effect between the remdesivir group and the placebo group was significant, the effect would not be enough to stop transmission of the virus on a population basis. Health Canada made the decision to use remdesivir in severe COVID-19 disease cases.

Merck introduced molnupiravir, another antiviral drug against Covid-19

Molnupiravir was approved in the UK as an antiviral drug for early and moderately severe cases of Covid-19. It is difficult to get data on the Merck’s molnupiravir drug. But this publication states that there is a 50% reduction of mild to moderate cases of Covid-19 cases with molnupiravir. Professor Peter Horby from the University of Oxford pointed out “the proportional reduction in the risk of hospitalisation or death is impressive. But it is important to remember that the absolute risks were 14% reduced to 7%, so quite a lot of people need to be treated to prevent one hospitalisation or death.” Others pointed out that the side-effects are very similar between placebo pills and molnupiravir pills. Overall molnupiravir appears to be a useful addition in the treatment of Covid-19.

Higher doses of vitamin D3 effective in treating and preventing Covid-19

Higher doses of vitamin D3 will mitigate the course of influenza and of Covid-19 coronavirus. Researchers outlined 3 mechanisms of how vitamin D works:

  • Maintaining tight epithelial junctions making it more difficult for the Covid-19 coronavirus to penetrate.“
  • Killing enveloped viruses through induction of cathelicidin and defensins.” These powerful antiviral polypeptides can kill viruses that have invaded the bloodstream within 1 to 2 days.”
  • And reducing production of proinflammatory cytokines by the innate immune system, thereby reducing the risk of a cytokine storm leading to pneumonia.” It is people who get the viral pneumonia that are at a high risk of death. By bringing the blood level up to the higher range of normal, between 50 and 80 ng/mL, patients that have encountered Covid-19 coronavirus are more likely to survive.
Drugs that May be Useful in the Treatment of Covid-19

Drugs that May be Useful in the Treatment of Covid-19

Conclusion

Beside distancing, the wearing of masks and frequent hand washing other methods are emerging to fight the virus that causes Covid-19. Vaccinations are very effective, although they are less effective in patients with a weakened immune system. But there are also drugs that may be useful in the treatment of Covid-19. Newer studies have shown that the antidepressant Luvox has a mild effect on helping Covid-19 patients. Last year remdesivir came into the market. And this year Merck added molnupiravir, another antiviral pill. We should not forget that vitamin D3 is an effective antiviral vitamin. But it is only effective, provided the patient takes enough vitamin D3. The blood level must reach the high normal level of 50-80 ng/mL vitamin D in the blood. Up to now vaccinations and booster shots are the most effective way to prevent Covid-19 infection. Vitamin D3 and molnupiravir are also very effective.

Part of the above was previously published here.

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May
15
2021

Research about Side Effects of the AstraZeneca Vaccine

Research about side effects of the AstraZeneca vaccine revealed some worrisome facts. An article that appeared in the German “Frankfurter Allgemeine Zeitung” explained that people should not worry about the vaccine.

The heading of the article was:” People no longer have to be afraid of the AstraZeneca-Vaccine.” But subsequently it describes how vaccinating with the AstraZeneca vaccine against Covid-19 developed blood clots in some people. Researchers at the University of Greifswald examined 7 cases where following the vaccine blood clots developed.  Dr. Andreas Greinacher is Head of the department of Transfusion Medicine in Greifswald, Germany. He said that blood clots are extremely rare following vaccinations. The 7 people who did form clots in sinuses (big vein structures) of the brain had all antibodies against platelets. Normally platelets help with hemostasis for wounds, but when specific antibodies bind to platelets, they can cause blood clots.

Research about side effects of the AstraZeneca vaccine identified blood clots as a problem

The Greifswald medical team said that they know how to treat this blood clot condition when it occurs. They are using blood clot dissolving medication like heparin and warfarin to dissolve the clots. But if this treatment is not instituted right away, the patient could get a stroke or pulmonary emboli, which is a life-threatening condition. Normal minor side effects of the vaccine occur on the first and second day after the vaccination. If blood clots appear in brain veins, symptoms of severe headaches develop on day 4 or 5 following the vaccination. Other patients might develop a painful leg due to a blood clot in the leg veins. If this should happen, the patient must present immediately at the emergency department of a hospital. Physicians will start anticoagulation therapy right away. The 7 patients who developed blood clots did so between day 5 and 14 following the AstraZeneca vaccination.

European decision to reinstate the AstraZeneca vaccine

The European Medical Agency stated that the benefits would outweigh the risks of the AstraZeneca vaccine. They recommended reinstatement of vaccinations with the vaccine. However, there remain problems with the vaccine. First, the effectiveness of the vaccine was initially determined to be 79%, but retesting showed it is only 76%. Next the Paul-Ehrlich-Institut that monitors complications of medical procedures in all of Germany determined 31 cases of blood clots. 9 patients died from them.

Interestingly, the EMA has reversed their opinion about the AstraZeneca vaccine on April 6, 2021 as can be seen from this press statement. Now they are saying that there is a clear association between the vaccine and rare blood clots in the brain.

In the US the CDC and FDA have not approved the AstraZeneca vaccine. The CDC also said that the Johnson-Johnson’s vaccine should be put on hold until a re-examination of the blood clot issue is clarified.

Discussion

The Pfizer and Moderna vaccines are pure RNA vaccines that are known to have very few complication rates. Researchers stated that only very few people develop clots in their brain or leg veins. They also stated that the majority of people benefit from the AstraZeneca vaccine. This is a simplification. There are other vaccines that doctors can use as alternatives that do not produce clots. It would be better to ask why there is clot formation with the AstraZeneca Vaccine!

The AstraZeneca vaccine contains a DNA adenovirus

The AstraZeneca vaccine contains remnants of a DNA virus, namely an adenovirus. Researchers added the gene for the coronavirus spike protein to the DNA adenovirus.

The DNA shell from the adenovirus helps to protect the vaccine at fridge temperatures, which increases the shelf life of the vaccine. But as with other DNA vaccines there are more complications possible. Researchers reviewed this  question already 10 years ago.

In the end we are still faced with RNA vaccines against Coved-19 that work, versus a DNA vaccine that has possible complications with blood clots. I for one would not accept anything else but an RNA vaccine that does not have the clot formation side effect. I feel that the authorities should stop the AstraZeneca vaccine for now. The researchers should carry out further studies to see whether improvements can make the vaccine safer.

Research about Side Effects of the AstraZeneca Vaccine

Research about Side Effects of the AstraZeneca Vaccine

Conclusion

The AstraZeneca vaccine contains a deactivated DNA adenovirus. Researchers added the gene for the coronavirus spike protein to the adenovirus. This is a completely different approach from the RNA vaccines that do not have these side effects. The fact that some patients developed blood clots is likely explainable on the grounds that they received a DNA vaccine. In my opinion the authorities released the AstraZeneca vaccine prematurely. They should put a hold on this vaccine until scientists can develop improvements to the vaccine. In the meantime, people should receive the safer RNA vaccines.

To continue vaccinating with AstraZeneca vaccine is unacceptable

I disagree that governments allow a vaccine that has serious complication rates for which doctors offer anticoagulation therapy. It is only a matter of time that a few deaths occur, because the blood clots escaped diagnosis. The company has now renamed the vaccine as Vaxzevria. This seems to be a move of AstraZeneca to move away from the complications of the AstraZeneca vaccine. This does nothing to help solve the problem with the blood clots that don’t only occur “in a few cases”. We are dealing with a serious side effect, and you should ask yourself the question, whether it is worth the risk.

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Oct
17
2020

What can Happen to Your Body Over Months of Isolation

A recent article by CNN describes what can happen to your body over months of isolation at home. The article is rather negative showing all the possible things that can go wrong. I have been isolated as well since March 2020. I handle the isolation differently than described in the article. I will comment to each point what can be done differently to avoid the complications mentioned.

Muscle loss

The CNN article makes the point that inactivity can make you lose muscle bulk within only one week. A lack of exercise weakens your muscle strength. And muscle strength has been associated with longevity.

My comment:

I do a brisk walk of 5 to 7 kilometers daily. This maintains my muscle bulk. But I have a treadmill in the basement and a couple of weights that I can use, if it rains outside.

There is a danger that heart and lungs get weaker

You need to raise your heart rate and you also need to perfuse your lungs through exercise. Many people do not like exercise. They sit in front of the TV for hours or they surf the net on the computer. Even just reading a book does not give you enough exercise to get your heart rate up and increase your lung perfusion.

My comment:

A brisk walk with proper distancing gives you fresh air, exercises your muscles, your heart and your lungs. It maintains your cardiovascular fitness.

Weight gain

Being home all the time allows you to look into the fridge more often and eat snacks that are processed. People tend to eat more often than 3 times a day. The end result is that you gain weight. In the beginning of the epidemic people stocked up on non-perishable foods. Often they contain more sugar and carbohydrates. Consuming these foods leads to weight gain. Wearing masks, frequent hand washing, isolation practices and change of normal routines makes people get stressed. Stress leads to overeating and weight gain.

My comment:

In the last 6 months that I did home isolation my body mass index (BMI) stayed in the 21.0 to 22.0 range. I ate three meals a day. I avoided processed foods as they are overloaded with sugar, salt and refined carbs. Once a month I do a 5-day fasting mimicking diet according to Dr. Longo. This ensures that my BMI stays within the range I indicated. Otherwise I eat a Mediterranean diet, which is anti-inflammatory.

Your posture could suffer

When you are seated in front of the computer or the TV you tend to engage in poor postures. This can lead to strains of your back, neck, shoulders and hips. Staring at the computer screen or the TV can also give you eye strain.

My comment:

The key is movement, such as getting up and walking around; doing other activities like lawn mowing, weed eating or doing dishes. This interrupts any longer stretch of bad posture.

Your sleep quality can suffer

The more exposure to sunlight during the day you get, the more vitamin D you produce in the skin. Some people lack the necessary enzymes in the skin to convert cholesterol into vitamin D. But exposure to sunlight also helps to reinforce your diurnal hormone rhythm. This is also called circadian rhythm. Avoid blue lights (TV, computer, iPhones etc.) in the evening before bedtime as this can interfere with a deep sleep later. Also go to bed early enough (between 10 and 11 PM) to allow your circadian rhythm to take over.

My comment:

Some people (above the age of 60) benefit from 3 mg of melatonin at bedtime. After the age of 60 people no longer produce enough melatonin in the pineal gland. If I wake up in the middle of the night, I take another 3 mg of melatonin prior to 3AM. Caution: after 3 AM melatonin can give you a bit of a hangover in the morning.

Your brain can slow down

The brain needs nutrition and exercise. Exercise can eliminate certain amino acid by-products that otherwise turn into neurotoxins. With exercise you even prevent neurotoxins to enter the brain.

My comment:

I find that I must at least do a brisk walk of 4 kilometers a day. It prevents back pain, helps me sleep better and keeps my mind clear. But as mentioned earlier I prefer doing a brisk walk for 5 to 7 kilometers a day. In the past (prior to March 2020 when the Covid-19 pandemic started) I went to the gym every day. When it finally reopened, they had one Covid-19 case at the gym. I decided that it is too dangerous to go back to the gym until a safe Covid-19 vaccine is available in the summer of 2021. I feel the same way about flying. It is not worth the risk. I can just stay local and do my own program. The pleasure of traveling can wait until the summer of next year.

What can Happen to Your Body Over Months of Isolation

What can Happen to Your Body Over Months of Isolation

Conclusion

A recent CNN article described the dangers of passively staying in home isolation. I felt that this article was on the negative side. I found that by including a regular brisk walking program into my daily lifestyle the day got more structured. I felt I had more energy and I had no aches or pains. If I spent too much time watching TV or spending in front of the computer, I developed back aches and felt sluggish. I incorporated a 5-day fasting mimicking diet according to Dr. Longo once per month into my regular Mediterranean diet. This allowed me to keep my body mass index in the 21.0- 22.0 range. Doing what I described above I could continue to hold my weight, have energy and stay pain free for many more months. But when the Covid-19 vaccine arrives in spring/summer of 2021 I hope that things will return to normal.

Jul
25
2020

The Immune System Changes With Age

When we are young, we do not think about our immune system, but the immune system changes with age. When we are older than age 60, we notice that we may be taking longer to recover from a flu.

How does the immune system work?

There are two parts to the immune system, the innate immune system and the adaptive immune system. The innate immune system works to protect us from bacteria, viruses, toxins and fungi from the time we are born. The adaptive immune system uses B lymphocytes from the bone marrow to produce antibodies against viruses. This provides often lifelong immunity against this specific virus, but takes 3 to 5 days to kick in. Vaccinations can also trigger antibody production to protect us from viruses in the future. Both the adaptive and the innate immune system work together closely.

What are the ingredients for a fully functioning immune system?

The immune system consists of various immune organs that are distributed throughout the body. The bone marrow produces lymphocytes, granulocytes, macrophages, eosinophils and basophils. The adenoids in the back of the nasal passages and the tonsils in the back of the throat contain a lot of lymphocytes that are ready to protect us from colds and flus. We have lymph nodes throughout the body and they are connected with lymphatic vessels. The lymph nodes filter the lymph fluid that travels in the lymphatic vessels.

Other sites of lymphocyte production

The small intestine contains the Peyer’s patches, a collection of lymphocytes that protect our gut from invading bacteria or viruses. The spleen is located in the left abdominal cavity under the diaphragm. It removes old red blood cells and provides lymphocytes for the immune system. The thymus gland is located between the breast bone and the trachea. It changes bone marrow derived lymphocytes (B cells) into T lymphocytes that can process antigens from viruses and pass them on to the adaptive immune system for a full antibody response.

Cellular interactions between various players of the immune system

Back in the 1970’s it was already known that there were bone marrow derived B lymphocytes and thymus processed T lymphocytes. We knew then that B cells were involved in antibody production (adaptive immunity). T lymphocytes were thought to turn into killer T lymphocytes to kill cancer cells. But some T cells were T helper cells to process antigen and present it to B lymphocytes for antibody production.

More research since then refined what we know about the cells of the immune system.

Natural killer cells (NK cells)

Natural killer cells (NK cells) are part of the innate immune system. They attack cancer cells and cells that are infected by viruses. It takes about 3 days for their full action to develop. NK cells utilize the cell surface histocompatibility complex to decide whether to destroy a cell or not. T cell lymphocytes do not have the ability to do that. In the Covid-19 coronavirus situation NK cells play an important role to combat the disease right away.

Monocytes

They are large white blood cells that can differentiate further into macrophages and dendritic cells. Monocytes are part of the innate immunity, but they have an antigen presenting capability, which makes them also part of the adaptive immunity.

Memory T cells

The immune system learns to adapt to viruses and bacteria that we have come in contact with. The reason for the memory of the immune cells are the memory T cells. They replicate like stem cells, which keeps a clone of T lymphocytes, T helper cells and cytotoxic T killer cells in the background. They circulate through the body including the lymph glands and the spleen.

Immunosenescence as we age

There are several factors that come together, which age our immune system. The term for this is “immunosenescence“. There are genetic differences and differences due to the sex hormones. Estrogens increase the response of the immune system. In contrast, progesterone and androgens (including testosterone) decrease the immune response. This may be the reason why women tend to live longer than men.

As we age there are more and more memory T cells (both cytotoxic T cells and T helper cells). This weakens the formation of the natural killer cells (NK cells) of the innate immune system. Even the initiation of the adaptive immune system can be slower when we age and also the response to the flu vaccine. In addition, this can pave the way to autoimmune diseases.

The immune system changes with age: Evidence of immunosenescence

The following 3 factors show whether a person has immunosenescence:

  • The immune system has difficulties to respond to new viruses/bacteria or to vaccines
  • Accumulation of memory T cells crowding out cells of the rest of the immune system
  • Low-grade inflammation that is chronic and persists (“inflamm-aging”)

The process of immunosenescence starts with the involution of the thymus gland around the time of puberty. At that time the sex hormone secretion is highest. At the same time a growth factor from the bone marrow and the thymus gland decreases. It has the name interleukin-7 (IL-7). The end result is a slow decrease of the innate immune system with age and a more substantial weakening of the adaptive immune system due to a lack of naïve T and B cells. 

Chronic viruses can weaken the immune system further

The varicella herpes zoster virus causes chickenpox. In some people the chickenpox virus can persist, but the immune system actively keeps it controlled. In the 60’s or 70’s when the immune system is weakened from aging, there can be a flare-up as shingles, a localized form of the chickenpox virus.

Another virus, the human cytomegalovirus can cause a chronic infection that often persists lifelong. In this case the immune system is chronically weakened because of a massive accumulation of T memory cells, which keeps the human cytomegalovirus infection at bay.

What we need when the immune system changes with age 

Vitamin A

Both the innate and adaptive immunity depend on vitamin A and its metabolites. The skin cells and mucosal cells function as a barrier, which is important for the innate immunity. The skin/mucosal lining of the eye, the respiratory tract, the gastrointestinal and genitourinary tracts help the innate immunity to keep viruses and bacteria out of the body. Vitamin A is important to support macrophages, neutrophils and natural killer (NK) cells. In addition, vitamin A supports the adaptive immune system, namely T and B lymphocytes, so that the body can produce specific antibodies against viruses.

I do not take vitamin A supplements as I eat diversified foods like spinach, vegetables, poultry, Brussels sprout, fish and dairy products that contain vitamin A and carotenoids.

Vitamin C

This vitamin is a powerful antioxidant. It can neutralize reactive oxygen species, which are produced when the immune cells fight viruses and bacteria. Neutrophils, lymphocytes and phagocytes are all supported by vitamin C. Vitamin C and E co-operate in their antioxidant functions. Vitamin C is essential for a strong antibody response with bacterial or viral infections. I take 1000 mg of vitamin C once daily.

Vitamin D

The immune system is very dependent on vitamin D as the immune cells all contain vitamin D receptors. People who have less than 10 ng/mL of vitamin D in the blood are vitamin D deficient. They have much higher death rates when they get infected with the Covid-19 coronavirus.

Vitamin D regulates the expression of target genes. At the center is the vitamin D receptor, which is a nuclear transcription factor. Together with the retinoic X receptor (from vitamin A) the vitamin D receptor binds small sequences of DNA. They have the name “vitamin D response elements” and are capable of initiating a cascade of molecular interactions. The result is a modulation of specific genes. Researchers identified thousands of vitamin D response elements that regulate between 100 and 1250 genes.

You need enough vitamin D for your immune system

When enough vitamin D is present in the blood (more than 30 ng/mL) the immune system releases the peptides cathelicidins and defensins, which effectively destroy bacteria and viruses.

Vitamin D has mainly an inhibitory function regarding adaptive immunity. It inhibits antibody production from B cells and also dampens the effect of T cells. Researchers reported that vitamin D3 is useful in the treatment of autoimmune diseases.

I am a slow absorber of vitamin D3 as repeat blood vitamin D levels showed. I need 10,000 IU of vitamin D3 daily to get a blood level of 50-80 ng/mL (=125-200 nmol/L). This is the higher range of normal. Everybody is different. Ask your physician to check your blood level of vitamin D. Toxic vitamin D blood levels are only starting above 150 ng/mL (= 375 nmol/L).

Vitamin E

This is a vitamin that is fat soluble and helps the body to maintain its cell membranes. But researchers found that vitamin E also stimulates the T cell-mediated immune response. This is particularly important for the aging person to prevent respiratory tract infections. I take 125 mg of Annatto tocotrienols per day (this is the most potent form of vitamin E).

Vitamin B6

This vitamin is important for antibody production by B cells. Vitamin B6 regulates the metabolism of amino acids, which in turn form proteins. Antibodies and cytokines require vitamin B6. The T helper immune cells that initiate an adaptive immune response depend on vitamin B6 as well. I take a multi B complex vitamin (Mega B 50) twice per day, so I supplement with a total of 100 mg of vitamin B6 daily.

Folate

Folic acid is a coenzyme for the metabolism of nucleic acids and amino acids. Studies in humans and animals have shown that folate deficiency leads to increased susceptibility to infections. People with folate deficiency develop a megaloblastic anemia with immune weakness that leads to chronic infections. With my B complex supplement I get 2 mg of folic acid daily.

Vitamin B12

Methylation pathways depend on vitamin B12 as a coenzyme. Vitamin B12 is also involved as a coenzyme in the production of energy from fats and proteins. In addition, hemoglobin synthesis depends on vitamin B12. Patients with vitamin B12 deficiency develop pernicious anemia. These patients also have a weak immune system due to natural killer cell activity suppression and because circulating lymphocyte numbers are significantly decreased.

Treatment with cyanocobalamin reverses the immune weakness rapidly and treats pernicious anemia at the same time. I take 50 micrograms twice per day as part of the Mega-B50 multivitamin tablet. But I also inject 1000 micrograms of vitamin B12 every 6 months subcutaneously to be sure it is absorbed into the body. In older age the intrinsic factor from the stomach lining, which is required for absorption of vitamin B12 in the small intestine, can be missing, leading to vitamin B12 deficiency despite swallowing supplements.

Minerals required for a good immune response

Researchers identified five minerals that are essential for a strong immune system. They are zinc, iron, selenium, copper and magnesium.

Zinc

Zinc is important for a normal function of the innate and adaptive immune system. As zinc cannot be stored in the body, taking regular zinc supplements (30 to 50 mg daily) is important. I take 50 mg of amino acid chelated zinc daily.

Iron

Iron is important for cell oxygen transport and storage, DNA synthesis and for mounting an effective immune response. In particular it is the T cell differentiation and proliferation where iron is needed. Iron deficient people get a lot of infections because the immune system is paralyzed. I eat one spinach salad or steamed spinach daily, which gives me enough iron supply per day.

Selenium

Selenium is a trace mineral that is important for a normal immune response and for cancer prevention. When selenium is missing, both the adaptive and innate immune system are suffering. In this case viruses are more virulent. With selenium supplementation cell-mediated immunity is improved and the immune response to viruses is more potent. I take 200 micrograms of selenium per day.

Copper

Deficiency in copper results in a very low neutrophil blood count and causes susceptibility to infections. Copper is a trace mineral that participates in several enzymatic reactions. It is important for the innate immune response to bacterial infections. A well-balanced Mediterranean diet contains enough copper, which is why I do not supplement with extra copper.

Magnesium

An important cofactor for vitamin D in the body is magnesium. Magnesium participates in many enzymatic reactions. Between vitamin D and magnesium, the immune system is strengthened. I take 150 mg of magnesium citrate twice per day. By the way, magnesium also helps us to get a restful sleep, if we take it at bedtime.

Other dietary factors that strengthen the immune system

Polyunsaturated omega-3 fatty acids

It is important to note that polyunsaturated omega-3 fatty acids are essential for the body and help to modulate the immune system. I take 1800 mg of omega-3 (EPA/DHA) twice per day. I also like to eat fish and seafood at least 3 times per week.

Probiotics

Prebiotics benefit both the innate and the adaptive immune system. They strengthen the epithelial gut barrier, which is an important innate immune defence. Probiotics also lower the risk for Clostridium difficile gut infections. I take one probiotic every morning.

The Immune System Changes With Age

The Immune System Changes With Age

Conclusion

The immune system consists of different organs like the bone marrow, the spleen, lymph glands, Peyer’s patches in the gut, the thymus gland and more. There is the innate immune system, which responds immediately to a virus like the Covid-19 coronavirus. The adaptive immune response involves antibody production against, for instance, the measle virus or the mumps virus. With the aging process the immune system slows down (immunosenescence). This involves an accumulation of memory T cells and a depletion of natural killer cells (NK cells). This means that the innate immunity is getting weaker as we age and chronic inflammation occurs more often. This is the reason why people above the age of 65 get more severe symptoms from the Covid-19 coronavirus. They are also more affected by influenza-type illnesses.

Take supplements to strengthen the immune system

I reviewed the cofactors of a healthy immune system in some detail. It is important that you pay attention to these, particularly the vitamin D3 intake. With a strong immune system, we can survive viral infections better, including the current Covid-19 coronavirus. Future research will likely detect how to reactivate a sluggish immune system in older people. This way vaccination responses following flu injections will become more reliable in seniors.

Dec
07
2019

The Use Of Oncolytic Viruses For Cancer Treatment

In the first place, preliminary experiments indicate that the use of oncolytic viruses for cancer treatment may become a reality. There are several lines of research that point to the fact that oncolytic viruses can make a difference in treating incurable cancer patients.

Notably, Canadian researchers had reported in 2011 that oncolytic viruses created by genetically modifying smallpox vaccine viruses would enter tumor cells of patients, but not damage normal cells. Specifically, a high percentage of the end stage patients responded with tumor regression.

Shortly after Mayo Clinic physicians were desperate when two patients with end stage multiple myeloma, a vicious bone tumor, did not respond to chemotherapy. Significantly, they tried something unconventional: high doses of the measles vaccine in an attempt to stimulate the immune system. Here is an overview from 2014 that shows that many different cancers respond to various immunological approaches.

Study from Holland regarding end stage melanoma patients

Here is a small human study involving end-stage melanoma patients treated with the oncolytic virus T-VEC combined with pembrolizumab (Keytruda). It is important to realize that Keytruda helps to reactivate a T-cell response to the cancer cells. In this case the cancer cells absorb the oncolytic virus (T-VEC), but it leaves normal cells alone. Inside the cancer cells the oncolytic virus multiplies and destroys the cancer cells. In this 2017 study 21 patients with terminal, nonresectable melanoma received treatment with T-VEC and Keytruda. Specifically, 62% of the patients showed an objective response to the treatment. Moreover, 33% fulfilled the criteria of an immune-related response. In the past terminal patients like these had a 0% response to radiotherapy or chemotherapy.

History of research about oncolytic viruses

To begin with, in 1912 rabies virus treatment against cervical carcinoma was a first attempt to treat cancer. Researchers conducted many experiments between 1950 and 1970 with wild type or naturally attenuated viruses. This included, for example, hepatitis A and B viruses. In 1991 cancer researchers developed the concept of genetically engineered oncolytic viruses. Today cancer researchers know that the protection mechanisms in most cancer cells have deficiencies. This involves the interferon‐beta signal pathway. Having said this, there is an opportunity to let oncolytic viruses destroy cancer cells, while normal cells stay unaffected. An oncolytic virus that cancer experts use in human cancers is the genetically engineered herpes simplex virus type I (HSV‐1). Others that cancer researchers developed have strange names like T‐Vec, G47∆, JX594, CG0070 and Reolysin.

Various cancers that researchers treated with oncolytic viruses

Here are a few examples of cancers where researchers used oncolytic viruses to exert a significant therapeutic effect.

Glioblastoma

Glioblastoma is a deadly form of a brain tumor, which has a high rate of mortality. Researchers have investigated new avenues to treat this cancer. Researchers tested the genetically engineered dendritic vaccine. Initial clinical trials showed significant effectiveness compared to non-treated controls. In a large phase 3 clinical trial 331 patients with newly diagnosed glioblastoma received treatment at the time of neurosurgery with dendritic cell vaccine. 30.2% of the patients were still alive and doing well after 3 1/3 years. Without the added vaccination procedure all of these patients would have died in the past because of the aggressiveness of the glioblastoma.

Multiple myeloma

Researchers could cure multiple myeloma and other cancers by using the measles vaccine. Here is a report by the popular press about two women who had multiple myeloma. One woman got cured by high doses of a measles vaccine. The other women experienced some relief, but did not survive.

This publication explains that oncolytic viral therapy of cancer is a lot more complicated than originally thought.

Prostate cancer

Researchers found that vaccines against prostate cancer were effective with the combination of oncolytic virus therapy with regular anti-cancer treatments. But oncolytic virus therapy alone has a poorer prognosis than a combination of chemotherapy or radiotherapy with oncolytic virus therapy.

Cervical cancer

The high-risk HPV16 strain most often causes cervical cancer. The HPV (human papilloma virus) vaccine targets patients with previous exposure to HPV16. However, researchers have noticed that in some cases a phenomenon called the “HPV immune escape” has allowed in some vaccinated women to still develop cervical cancer. Now a group of researchers are investigating how the vaccine could be improved by finding out how the immune system is being tricked in these cases by the HPV virus to bypass the antibodies of the vaccine.

Pancreatic cancer

This cancer is very difficult to detect in the early stages, and as a result the outlook for chemotherapy or radiotherapy is extremely poor. Researchers have used several approaches as an alternative to conventional therapy. Immunotherapy is an option. Mayo clinic researchers have already announced that the measles vaccine approach will likely be applicable to pancreatic cancer treatment as well in the near future. However, other clinical trials are on the way to use alternative vaccination procedures.

Neuroblastoma, glioma and melanoma

This link shows that the FDA has accepted engineered oncolytic herpes virus (engineered to secrete GM-CSF) as a treatment against melanoma. Other approaches with engineered bacteria can affect neuroblastoma and glioma.

Survival data using oncolytic viruses for cancer treatment

Cancer researchers have completed a number of smaller clinical trials at this point. One of them describes end stage melanoma (stage III and IV) where the only treatment was with the oncolytic virus T‐Vec. The overall response rate compared to the control, which was only 5.7%, the experimental group with T-Vec was 26.4%. This is considered a good response rate given that we are dealing with end stage melanoma patients.

Mechanism of how oncolytic viruses stimulate the immune system to overcome various cancers

As mentioned above oncolytic viruses multiply in the cancer, once they have been incorporated. This leads to cancer cell death. It exposes the dead cancer tissue to the immune system. What helps in the process is that inhibitory proteins from the cancer cells that used to inhibit the immune system are no longer provided by the dead cancer cells. The end result is that the immune system mounts a formidable response against the cancer cells through killer T cells. This immune response also affects remote metastases of the same histological cancer type. This review article summarizes how oncolytic viruses work for cancer cell destruction and how this method can be combined with other treatment modalities.

The Use Of Oncolytic Viruses For Cancer Treatment

The Use Of Oncolytic Viruses For Cancer Treatment

Conclusion

Currently various cancer centers are involved with clinical trials in humans to test the power of oncolytic viruses. What cancer researchers have learnt is that oncolytic viruses are a useful tool to kill cancer cells. But the immune system of cancer patients is in a suppressed state. Pembrolizumab (Keytruda) is a medication that will stimulate the immune system by stimulating killer T cells to destroy cancer cells. The combined effect of killing cancer cells with oncolytic viruses and stimulating the immune system is the big news. This has been the breakthrough that cancer researchers have been waiting for. Now several clinical trials are on the way where survival rates for cancer patients given the new combination therapy are assessed.

Oncolytic virus therapy here to stay

It is a treatment which is no longer a thought model with animal experiments. Well known medical centers are using it in patients, and as the results become more obvious, it will very likely become a new treatment modality for cancer.

Jan
31
2013

Staying Healthy During Exotic Travel

A study of 82,825 ill travelers from Europe, North America, Israel, Japan, Australia and New Zealand was published who were interested in staying healthy during exotic travel. They had traveled the world between June 1996 and August 2011. The data was based on the GeoSentinel surveillance network database. There were 3,655 patients (4.4%) who were seriously sick with one of 13 tropical diseases. There were 13 deaths (=0.4%), 10 of which were from malaria. Two died from melioidosis. This is an infectious disease caused by a bacterium found in soil in Southeast Asia (including Thailand, Laos, southern China, Singapore, Malaysia, Burma and Vietnam), Taiwan and northern Australia. One person died from severe dengue. The interesting fact is that there was not a single case of Ebola virus, although this is a highly publicized and lethal illness in Africa. The majority of travelers sustained malaria and typhoid.

The tropical diseases were either due to viral illnesses, bacterial infections or protozoan infections.

Frequent viral illnesses encountered by visitors to Asia were dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS); avian influenza, Lassa fever as well as other tropical hemorrhagic fevers, Japanese encephalitis including other tropical encephalitis cases, Rift Valley fever and yellow fever.

This is a list of the bacterial infections that were reported: Anthrax, Carrion’s disease (=Bartonella bacilliformis), epidemic typhus, leptospirosis, melioidosis, murine typhus, paratyphoid fever, plague, relapsing fever, scrub typhus, spotted fever group rickettsioses and typhoid fever.

An interesting side-note is that even in familiar places like Hawaii leptospirosis is re-emerging as this link shows. So, it is important for visitors to Kauai and the Big Island of Hawaii (Waipio valley) to refrain from swimming in streams or natural ponds and to not expose your face to cascading waterfalls as leptospirosis can enter through the eyes, the nose, the mouth and scratches on the skin.

Finally, the following protozoan infections were found frequently: East African sleeping sickness, falciparum malaria and Plasmodium knowlesi malaria.

Staying Healthy During Exotic Travel

Staying Healthy During Exotic Travel

Each travel region has its special infection characteristics. With travel to Central America infectious diseases ranked in decreasing frequency like this: typhoid fever, leptospirosis, falciparum malaria and paratyphoid fever. In the Caribbean falciparum malaria was followed by typhoid fever, leptospirosis and paratyphoid fever. In South America the highest on the list was again falciparum malaria, followed by typhoid fever, paratyphoid fever and leptospirosis. In Sub Saharan Africa the highest number of falciparum malaria cases were registered (2633 of them), followed by 42 cases of typhoid fever, paratyphoid fever and leptospirosis. In the Middle East only one case of falciparum malaria, one case of typhoid fever and 2 cases of paratyphoid fever were reported. In contrast there were many more infections reported in South Central Asia (India): 286 cases of typhoid fever, followed by parathyroid fever, falciparum malaria and leptospirosis. All of the cases of typhoid fever and parathyroid fever in India were adequately treated with antibiotics and no deaths resulted from that. This is an example where no vaccine is available for prevention, but swift medical treatment could help immediately when an infection had occurred.

In South East Asia (Malaysia, Philippines, Indonesia) leptospirosis was on top, followed by typhoid fever, falciparum malaria and parathyroid fever. North East Asia (Korea, Mongolia), had only 3 cases of typhoid fever and 1 case of paratyphoid fever. Oceania (Polynesia) reported 26 cases of falciparum malaria, followed by paratyphoid fever and typhoid fever.

Several interesting observations were made with regard to this study.

  1. Most patients with travel acquired tropical illnesses presented within less than 17 days at the doctor’s office at home and 91% of them had developed a fever.
  2. The spectrum of the tropical disease that was diagnosed and treated varied according to the geographic destination where the traveler had been, which is consistent with the observations mentioned above (different distribution of tropical diseases depending on which area was traveled). Visitors to West Africa had a high rate of falciparum malaria, visitors to India sustained largely enteric fevers; and leptospirosis,  scrub typhus and murine typhus were the dominant tropical diseases for visitors to South East Asia.
  3. Males were found to be less diligent in using chemoprophylaxis for malaria prior to their travel than females. Overall only a minority had attended a travel clinic prior to their travel for immunizations and chemoprophylaxis for preventable tropical disease such as malaria.
  4. Other global life-threatening diseases like meningitis, other forms of septicemia, severe bacterial pneumonia and legionnaires also have to be considered as they occurred in roughly 30% of returning travelers.
  5. Malaria was the largest percentage of the tropical diseases that travelers brought home and 67% of all cases were male patients. They were mostly visiting West Africa where they acquired malaria (typically from Nigeria,  Ghana and the Ivory Coast). As mentioned they accounted for 10 of the 13 deaths.

The authors recommend that travelers should prepare themselves for trips to the tropics and subtropics, preferable visiting one of the travelers’ clinics. The recommended procedures should be followed meticulously. Not all of the diseases can be prevented, but if the traveler turns sick, they should seek medical advice as soon as possible in the country where they travel as these physicians often have special expertise in these tropical diseases.

One of the comments of the study was that often people visit relatives and friends in an area where tropical disease exists without any chemoprophylaxis or vaccinations beforehand. The visitors were under the impression that prior living in the area as a child would still protect them now during the travel as an adult, which is not the case. This can be prevented by visiting a travel clinic well before the planned trip, so there is enough time for vaccinations and possible blood tests.  

More information on:

1. Traveler’s diarrhea:  http://nethealthbook.com/infectious-disease/parasites/travelers-diarrhea/

2. Parasites: http://nethealthbook.com/infectious-disease/parasites/