In the previous blog, we saw how our immune system deals with the virus. Now lets look at why it seems to take a fancy for a certain segment of the population, and few other facts and figures.
Effects of Aging on the Immune System
Aging appears to have little effect on the lymphatic system’s ability to remove fluid from tissues, absorb lipids from the digestive tract, or remove defective red blood cells from the blood. However, aging has a severe impact on the adaptive immune system. Before getting to see why and how exactly this happens lets first look at our adaptive immune response again in a bit detail.
Antibody-mediated (Humoral) immunity vs Cell-mediated immunity response
Adaptive immunity can be divided into antibody-mediated (humoral) immunity and cell-mediated immunity.
Antibody-mediated immunity involves proteins called antibodies, which are found in extracellular fluids, such as the plasma of blood, interstitial fluid, and lymph. B cells give rise to cells that produce antibodies.
Cell-mediated immunity involves the actions of a second type of lymphocyte, called T cells. Several subtypes of T cells exist, each responsible for a particular aspect of cell-mediated immunity. For example, cytotoxic T cells are responsible for producing the effects of cell-mediated immunity. Cytotoxic T cells have two main effects:
They lyse (break down) cells and
They produce cytokines. A cytotoxic T cell binds to a target cell and releases chemicals that cause the target cell to lyse. The major method of lysis involves a protein called perforin.
Antibodies do not necessarily protect against viral infections, because many viruses can spread directly from cell to cell and thus avoid encountering antibodies in the bloodstream. It is also known that persons who fail to make antibodies are very susceptible to bacterial infections but are not unduly liable to viral infections. Protection in these cases results from cell-mediated immunity, which destroys and disposes of body cells in which viruses are actively growing, thus depriving microorganisms of their place to grow and exposing them to antibodies.
Now that we are equipped with knowledge lets jump into how age effects our immune system and response.
One major cause of age-related immune deficiencies is thymic involution, the shrinking of the thymus gland that begins at birth, at a rate of about three percent tissue loss per year, and continues until middle age, when the rate declines to about one percent loss per year for the
rest of one’s life. At that pace, the total loss of thymic epithelial tissue and thymocytes would
occur at about 110 years of age. Thus, this age is a theoretical limit to a healthy
human lifespan. This process appears to be genetically programmed.
What regulates the adaptive immune response are Tregs or in other words Regulatory T Cells. They keep tabs and help in regulating or suppressing other cells in the immune system. Tregs suppress activation, proliferation and cytokine production of T cells, and are thought to suppress B cells and dendritic cells. Treg homeostasis depends on an intact thymic function as well and therefore thymic involution with age has a profound impact on the immune response regulation.
In many individuals, the ability of helper T cells to proliferate in response to antigens decreases. Thus, antigen exposure produces fewer helper T cells, which results in less stimulation of B cells and cytotoxic T cells. Consequently, both antibody-mediated immunity and cell-mediated immunity responses to antigens decrease. Both primary and secondary antibody responses decrease with age. More antigen is required to produce a response, the response is slower, less antibody is produced, and fewer memory cells result. Thus, a person’s ability to resist infections and develop immunity decreases.
This is one of the major reasons why most of the people
who are dying because of the Covid-19 virus are
the elderly. Their immune systems are severely
compromised due to the loss of thymic
epithelial tissue.
*23% of Italians are aged 65 years or older, the high case-fatality in Italy is somewhat explained by the demographic characteristics.
Declining production of new naive T cells (due to shrinking Thymus, where these T Cells mature) is thought to be a significant component of immunosenescence, the age-related decline in immune system function. The natural process of aging goes hand in hand with immuno-senescence, a degeneration of the immune system that is characteristic of a greater susceptibility to infections, an inadequate immune response to vaccinations, and an increased propensity for autoimmune diseases and cancers.
In fact, according to the U.S. Center for Disease Control (CDC), approximately 80 % of aged individuals are
afflicted with at least one chronic disease as a result
of a declination of immune function.
Lymphopenia (also known as lymphocytopenia ) is a term used to describe the state where you have a reduced level of a lymphocytes (Natural Killer Cells, B & T Cells). Lymphocytes (one group of White Blood Cells) play a decisive role in maintaining immune homeostasis (Tregs) and inflammatory response throughout the body. T cells make up the greatest proportion of lymphocytes, and T-cell lymphocytopenia is the most common. However, this condition can affect all three cell types. Viruses has been shown to induce apoptosis and subsequent depletion of lymphocytes due to this. Basic researches confirmed that chemicals (TNF-α, interleukin-6, and other pro-inflammatory cytokines) released during the immune response could induce lymphocyte deficiency. The virus might also directly infect lymphocytes, resulting in lymphocyte death. Lymphocytes also express the coronavirus receptor ACE2 and may be a direct target of viruses.
So if we put all of this together, it is a no-brainer why the demographic
which is most impacted by this disease are the elderly.
Effects of Stress on the Immune System
Psychoneuroimmunology. Yep that’s quite a mouthful but there is a field of study which focuses on connections between the immune system, the central nervous system, and the endocrine system. Why study this connection? Well our immune system cannot exist in isolation. After all, it has to protect the entire body from infection. Therefore, the immune system is required to interact with other organ systems, sometimes in complex ways. It needs to interact and coordinate with neurotransmitters, hormones, cytokines, and other soluble signalling molecules, enabling the mechanism of “crosstalk” between these systems.
One such hormone which has a significant and often detrimental impact on the immune system or rather the immune response is Cortisol. Cortisol is involved in around 20% of gene expressions in our body. Its ability to suppress T-Cells is so strong, it is even administered during transplants to suppress the hosts immune system so it won’t reject the donor organ. It is also used in many anti-inflammatory drugs.
So what has this to do with stress? One well-established interaction of the immune, nervous, and endocrine systems is the effect of stress on immune health. In the human vertebrate evolutionary past, stress was associated with the fight-or-flight response, largely mediated by the central nervous system and the adrenal medulla. This stress was necessary for survival. The physical action of fighting or running, whichever the animal decides, usually resolves the problem in one way or another. On the other hand, there are no physical actions to resolve in most modern day stresses. The effect of stress can be felt by nearly every organ system, and the immune system is no exception.
In a KFF Poll conducted in the United States, 45% of adults reported that their mental health has been negatively impacted due to worry and stress over the virus. As the pandemic wears on, it is likely the mental health burden will increase as measures taken to slow the spread of the virus, such as social distancing, business and school closures, and shelter-in-place orders, lead to greater isolation and potential financial distress.
Effects of Vitamin D on the Immune System
Vitamin D, a steroid hormone has important roles in addition to its classic effects on calcium and bone homeostasis. It is involved in more than 1000 different gene expressions in our body. Vitamin D can be obtained from the diet however it is mostly synthesized via endogenous synthesis. This process occurs in a sequence that starts in our skin following exposure to ultraviolet light from the sun and continues in the liver and kidneys, where the vitamin's active hormone (Calcitriol - D3) form is made. Since ultraviolet light (and cholesterol) is required for vitamin D synthesis, inadequate amount of sunlight is one of the major causes of vitamin D deficiency.
Multiple factors might affect vitamin D levels like age, being indoors, dark
skin (too much melanin slows down the absorption), sunscreen use, and
low cholesterol levels might impede vitamin D3 biosynthesis.
Factors affecting Vitamin D synthesis are:
Age
Efficiency of cutaneous biosynthesis of vitamin D declines with age. Older adults are 63 % more likely to have vitamin D deficiency and 46 % more likely to have vitamin D insufficiency than young adults according to this study.
Obesity
Obese individuals have greater than 50% less bioavailability of vitamin D compared to non-obese individuals based on this study. This is because vitamin D is a fat soluble hormone so it has greater difficulty being released into the bloodstream due to the extra surface area.
Latitude
Where we live makes a huge difference in the amount of UVB radiation availability. The farther we live from the equator, the harder it is to absorb UVB radiation, which means less of it reaches our skin to facilitate the production of vitamin D.
Skin Colour
Melanin, which is a natural sunscreen that protects us from the damaging effects of UVA also has a negative effect on our ability to produce Vitamin D. The darker the skin (more melanin), the longer one needs to spend in the sun to absorb UVB.
Vitamin D and the Immune connection
As we learned in the previous blog, SARS-CoV-2 virus enters our cells via the ACE2 receptor.This way the virus particles bind to numerous ACE2 molecules and sequester them from the cell surface, making them unavailable for other key physiological processes, such as blood pressure regulation, inflammation, body fluid homeostasis, among others due to over-expression of renin (an enzyme produced in the kidneys) and subsequent activation of the renin-angiotensin-system. This can also promote neutrophil infiltration, excessive inflammation, and lung injury. Once lung infection progresses to hypoxia, renin is released, setting up a vicious cycle of decreasing ACE2. Lower levels of ACE2 promote more damage, culminating in acute respiratory distress syndrome, or ARDS.
The beneficial effects of vitamin D on protective immunity are due in part to its effects on the innate immune system. Vitamin D plays an important part in the innate immune response. Vitamin D has numerous effects on cells within the immune system. It inhibits B and T cell proliferation, blocks B cell differentiation, immunoglobulin secretion and facilitates the induction of T regulatory cells. These effects result in decreased production of pro-inflammatory chemicals (Cytokines - TNFα, IL2, IL-17, IL-21 etc) and increased production of anti-inflammatory chemicals (Cytokines - IL4,5,10).
Given the importance of vitamin D for a functional immune system, its widespread insufficiency (and perhaps exacerbated in quarantine conditions, due to limited sunlight exposure), It is imperative to get adequate exposure to sunlight or maybe at least consider temporary
vitamin D supplementation.
The practice of quarantine began during the 14th century, in an effort to protect coastal cities from plague epidemics. Cautious port authorities required ships arriving in Venice from infected ports to sit at anchor for 40 days before landing. The origin of the word quarantine is from the Italian “quaranta giorni”, or 40 days.
Effects of Human Microbiome on the Immune System
We humans are mostly microbes, around 100 trillion of them. Microbes far outnumber our human cells. The number of genes in all the microbes in one person's microbiome is over 100 times the number of genes in the human genome.
It’s hard to do systems biology,
when we ignore 99% of the systems!!
The bacteria in the microbiome help digest our food, regulate our immune system, protect against other bacteria that cause disease, and produce vitamins including B vitamins B12, thiamine and riboflavin, and Vitamin K, which is needed for blood coagulation. It is is essential for human development, immunity and nutrition.
In the age of sterility, where people are told to clean their hands with antibacterial or antimicrobial soap, spray their bathrooms and kitchens with bleach and other sanitizers and wash their dishes and clothes at "germ-killing" settings is sure an effective way to keep germs at bay but what about all the health benefits these germs bestow upon us. According to the 'hygiene hypothesis', people who grow up in areas with high levels of sanitation lack normal evolutionary exposure to microbes, pollen and other microscopic things in the environment. The lack of that exposure (add to this cesarean births) negatively affects the development of their immune system, according to the hypothesis.
Considering we are more microbial than human, exposure to microbes is an essential part of being human. Most of our immune system is comprised of tissue that requires activation by the microbes we’re exposed to. This doesn't mean that we should not take hygiene seriously. What this simply means is we shouldn't go overboard with deploying antibacterial soap and germ-killing cleaning products, and other sterile habits which indiscriminately kill germs, including good bacteria that help maintain a strong and diverse microbiome. The more diverse our microbiome is, the healthier we are.
As we learned from the previous blogs, the chances of us having a match (lock) of a pathogen's 'key' are so astronomically high that it’s safe to say there’s one in our body somewhere. The problem however is finding it before the pathogen does irreversible damage and usually there is delay between the initial exposure to a pathogen and the production of large quantities of antibodies. If pathogens can reproduce rapidly during this delay period, they can impede normal body functioning and cause illness/disease.
Our immunity is built based on our exposure to pathogens not to mention repeated exposure, as our immune cells have a shelf life and we lose immunity over a period of time (hence the booster shot for vaccines). So it is rather imperative to get dirty (pun intended). Getting over obsessed with hygiene, sterilizing everything, not getting exposed to the beneficial micorbiome enough etc
is proving to be detrimental to our wellbeing.
Efficacy of wearing a mask
The virus is usually transmitted through droplets during sneezing or coughing. The vast majority of the droplets are less than 100 microns (0.1mm) across. Surgical masks are designed to prevent large droplets passing from one person's mouth to another person or surface. N95 respirators protect the wearer from breathing in particles between 0.1 micron to 0.3 micron in diameter. When fitted correctly the respirators filter 95 per cent of airborne particles.
Unlike N95 respirators, the disposable surgical masks and other masks most people use are not designed to block the very smallest particles from entering the nose and mouth. They do lower the risk of infection but it’s next to impossible to create a perfect fit. So the masks most people wearing are rather redundant and end up causing more harm than good.
Now that we are locked and loaded with all the relevant information and knowledge we need about the coronavirus, how our immune system functions, it is up to us how we approach our life in general. We all should go out and bask in the sunshine, get stuck into dirt and stop getting obsessed with being overtly hygienic to the point of getting sterile, eat a wide variety of foods, stop letting stress get to us, spend quality time with family and friends, do what gives us joy, learn to appreciate the little things in life and learn to be contended. Easier said than done eh, but we got to start somewhere right. Stay safe and stay healthy..
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