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.

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Aug
31
2013

Peanut Allergies Are Deadly

In the US 1.5 million suffer from peanut allergies (Ref.1). People who have peanut allergies have to avoid peanuts and foods that contain even traces of peanuts lifelong. Here is a recent example of a 13-year old girl who died at a camp when she tried food contaminated with peanuts. Before we discuss peanut allergies in detail, we need to review first how the immune system is functioning.

How the immune system is primed to develop an allergy

Our immune system knows the difference between our own body components and substances that come from the outside. Scientists call this tolerance to our own surface proteins; and scientists call it an immune reaction that is mounting as a reaction to anything different from the surface antigens. There are different cells that make up the immune system. One of the main working cells of the immune system are the lymphocytes, with B cells originating from the bone marrow producing antibodies when an immune reaction occurs. Antibodies fit like a lock and key to the surface of an antigen, in this case the peanut protein. T helper cells are T lymphocytes (thymus derived lymphocytes) that help the B cells to recognize the difference between the own protein components and the outside components. There are also T killer cells, which get activated when parasites or viruses enter the body. With regard to peanut allergies it is the B cells and T helper cells that interact and the B cells produce a powerful, very specific IgE antibody directed against peanut protein. There are memory B cells, which continue to produce these specific anti-peanut protein antibodies and cause severe allergic reactions when future exposure to peanuts (even traces) occurs. So, the more often a person who is allergic to peanuts encounters even traces of peanuts, the immune system will get boosted and produce even more antibodies of the IgE type through reactivated B memory cells (Ref. 2). 98% of the population does not react to peanut exposure with allergies, but the other 2% who may have genetic susceptibility factors that predispose them to this often develop life-threatening reactions (an anaphylactic reaction).

What is an anaphylactic reaction to peanuts?

The most extreme form of allergies involving IgE antibodies can cause anaphylaxis. In the beginning stages of a peanut allergy there may only mild symptoms such as hives on the skin, itching and tingling around the mouth, a runny nose, a scratchy throat, wheezing, stomach cramps, vomiting or diarrhea. However, with a more severe allergy an asthma attack can develop, blood pressure drops leading to fainting or shock and severe airway obstruction in the throat or lungs can cause suffocation.

I vividly remember an 11-year-old boy who was brought in by ambulance to the emergency room of the hospital where I was working as the on-call physician. He had a hard time talking as his throat was swelling up as part of his anaphylactic reaction, within minutes he passed out completely (shock). Fortunately an anesthetist was in the department and could intubate him very quickly. However, despite adrenaline treatment, oxygen  by artificial ventilation and high doses of corticosteroid drugs he did not wake up until 10 hours later. In retrospect it turned out that he had eaten some crackers of a familiar brand that he knew as being free of peanut flour. However, he had seen an ad that the same brand of crackers was available as cheese crackers and he tried one of these, which prompted his admission to the hospital. The parents read the ingredients later: the label on the cheese crackers noted in small print that the flour of the cheese crackers contained peanut flour! Always read labels, even if it is a familiar brand! Fortunately for this boy he did not have brain damage from the time of his unconsciousness. He has been extremely careful since and is reading labels and avoiding unknown food items.

Peanut Allergies Are Deadly

Peanut Allergies Are Deadly

Cross-reactions between peanuts and other allergens

Allergies can be made worse when a person has inhalant allergies from pollens of trees or grasses that can share protein components from protein found in foods. The latest findings are that there are cross allergies between Fenugreek and lupine, which are both legumes, as are peanuts, so there are common antigens present in their proteins. A mouse-testing model has shed more light on this. Fenugreek has been shown to control mild diabetes by improving insulin resistance, but it cannot be consumed by persons who are highly allergic to peanuts because of the cross allergy mentioned.

There are other possible cross allergies to legumes like lentils, soy and chickpeas.

Other factors that can cause allergies to get worse

In the past the RAST test was often used.  This is a blood test for common food allergies that can cause severe allergic reactions like egg, milk, peanut, tree nuts, wheat, crustacean shellfish and soy. However, since about 2010 this has been replaced by the more sensitive ImmunoCAP Specific IgE test. Children who have food allergies to egg, milk, wheat, nuts, peanuts and soy often outgrow these allergies when they age, in other words their immune system can develop tolerance to many of these foods. Not so with peanut allergies ! They tend to be very persistent.

The immune responses to food allergies are complicated as there are immediate type immune reactions and delayed type immune reactions. The immediate immune responses are investigated with the above mentioned ImmunoCAP Specific IgE test. The delayed immune responses can be measured using the ELISA test. Positive IgE antibody tests for peanut protein are a marker that the person affected likely has more other allergies and they should be investigated by a knowledgeable allergist in that regard (Ref. 2).

What complicates the allergy sufferers’ lives even more is the fact that new wheat varieties since the 1970’s, called Clearfield wheat have a much higher gliadin (gluten) and lectin content than the old wheat varieties. As a result of exposure to this new type of wheat gluten intolerance and leaky gut syndrome have increased substantially in the world population (Ref.3). In addition, genetically modified foods like soy, corn, sugar beets, canola and others have challenged the immune system of sensitive humans even more. We do know that some people can develop autoimmune diseases from GMO foods and modern wheat, and this may be the reason that a host of diseases that belong into this disease category (MS, rheumatoid arthritis, Hashimoto’s thyroiditis, ankylosing spondylitis etc.) are much more common now than in the past. The geneticists who developed GMO foods seemed to be unaware how sensitive the immune system is, which will detect a few different amino acid sequences in a protein mounting a strong immune response to it.

Treatment for peanut allergies

The key for sufferers from peanut allergies is to avoid exposure to it. Read labels and use common sense. If something is not labeled, do not be tempted to eat it. Peanut flour is often mixed into the dough of crackers, not being labeled properly or only in fine print. With peanuts the antibodies usually circulate in the blood life long as the B memory cells do not diminish and get reactivated very quickly on repeat exposure producing antibodies again. As exposure to peanuts can cause severe asthma or anaphylactic shock, it is important to carry an EpiPen with you and to know how to use it.

In Europe attempts have been made to develop an oral desensitization method for food allergies including peanut allergies, but it has not produced concrete results yet. Recently, however, research from Texas, USA showed that it is possible to desensitize patients with peanut allergy by oral desensitization. In Australia where food allergies are more prevalent than in the US, tolerance to peanut, nut and shellfish allergies is being pursued by oral immunotherapy. Another group in Australia has developed a vaccination method using peptides, which are a sequence of amino acids, but shorter than the full peanut protein. It appears that this is the future direction of  treatment for peanut and other IgE mediated allergies: a kind of vaccination treatment to induce competing antibodies, which will neutralize the allergic IgE antibodies.

Conclusion

Peanut allergies have become more troublesome as the food industry has mixed peanut flour into Thai sauces, drinks, cookies, crackers and such. The person allergic to peanuts must read food labels and eat as much single-ingredient natural food as possible. This goes against the tendency of food processors who produce foods with a long rat tale of ingredients. If you see a label “may contain nuts or peanuts”, stay away from this product, as it is safer. Always carry an EpiPen or Twinject with you, just in case you develop an anaphylactic reaction (you only have a few minutes to stop the allergic reaction with adrenaline). In the future vaccination with a peanut protein specific peptide vaccine as mentioned regarding the Australian research, will probably become the treatment of choice.

More information on status asthmaticus (an acute asthma attack): http://nethealthbook.com/lung-disease/asthma-introduction/asthma-treatment/

References

1. Adkinson: Middleton’s Allergy: Principles and Practice, 7th ed. Chapter: Food Allergy. © 2008 Mosby.

2. Mandell: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 7th ed.© 2009 Churchill Livingstone.

3. William Davis, MD: “Wheat Belly Cookbook. 150 Recipes to Help You Lose the Wheat, Lose the Weight, and Find Your Path Back to Health”. HarperCollins Publishers LTD., Toronto, Canada, 2012.

Last edited Nov. 7, 2014