Immune Theory
A key attempt at disparaging my writing during the C19 pandemic was that I wasn’t an immunologist, and that I couldn’t possible understand how the immune system works. My response typically explained that we were utilising a theory of immunity, and that none of us really knows for sure how the immune system(s) work.
Is our knowledge of human immunity based on a theory?
Our knowledge of human immunity is based on a scientific theory called the "immune theory of disease." This theory explains how the human immune system works to protect the body from invading pathogens such as bacteria, viruses, and parasites. The immune theory of disease has been extensively researched and tested over many years and is supported by a vast body of evidence.
The immune theory of disease states that the immune system is comprised of a complex network of cells, tissues, and organs that work together to defend the body against invading pathogens. This includes cells such as white blood cells, antibodies, and complement proteins, as well as lymphatic tissues such as the spleen, lymph nodes, and thymus gland.
The immune system is also able to recognize and remember specific pathogens it has encountered before, which allows it to mount a more effective response if the pathogen is encountered again in the future. This is the basis for vaccination, which works by introducing a harmless version of a pathogen to the immune system, allowing it to build immunity to the real pathogen.
Overall, the immune theory of disease is a well-established scientific theory that has been extensively researched and tested, and it provides a strong framework for understanding how the human immune system works to protect the body from disease.
How does the immune system know what is a pathogen so it can defend?
The immune system in theory has the ability to recognise and distinguish between different types of substances in the body, including pathogens (disease-causing agents) and harmless substances. It is suggested to do this by using a variety of specialised cells and molecules that work together to detect and respond to pathogens.
One key component of the immune system theory is the presence of molecules called antigens. Antigens are found on the surface of pathogens, as well as on other foreign substances that are not normally present in the body. When the immune system encounters an antigen, it triggers a cascade of events that leads to the activation of immune cells and the production of antibodies that can recognise and neutralise the pathogen.
Another important component of the immune system is the ability to distinguish between "self" and "non-self" cells and molecules. This is accomplished through the presence of molecules called major histocompatibility complex (MHC) proteins, which are found on the surface of cells in the body. The immune system is able to recognise and respond to cells that have abnormal MHC proteins, which may indicate that they are infected or cancerous.
In addition to these mechanisms, the immune system also has specialised cells called dendritic cells, which are capable of capturing and presenting antigens to other immune cells. This helps to ensure that the immune system can theoretically mount a targeted and effective response to pathogens.
Overall, it is suggested that the immune system is able to recognise and respond to pathogens through a combination of antigen recognition, detection of abnormal MHC proteins, and specialised cells that can capture and present antigens to other immune cells.
How does this compare to morphology theory?
The immune theory of disease, which explains how the human immune system works to defend the body against pathogens, is a distinct and separate theory from the morphology theory of disease.
Morphology theory, also known as the germ theory of disease, is a theory that explains how infectious diseases are caused by specific microorganisms, such as bacteria, viruses, and parasites. This theory proposes that microorganisms are responsible for causing diseases, and that the transmission of these microorganisms from one individual to another is what leads to the spread of infectious diseases.
While the immune theory of disease and the morphology theory of disease are related in that they both deal with the causes and mechanisms of infectious diseases, they are fundamentally different. The immune theory of disease focuses on how the body's immune system responds to pathogens, while the morphology theory of disease focuses on the microorganisms themselves and how they cause disease.
It's worth noting that both the immune theory of disease and the morphology theory of disease have been extensively researched, modelled and tested over many years and are supported by a vast body of evidence. These theories have been critical in advancing our understanding of infectious diseases and developing effective strategies for preventing and treating them. However, they are still theories, so claims that specific therapeutics such as vaccines have certain degrees of efficacy must be viewed from the stance that their foundation is built upon theoretical knowledge no matter how well supported such theories are in the “science” community/industry.
What about danger theory?
The danger theory of immunity is another scientific theory that seeks to explain how the immune system responds to threats. Those that know me will know that I prefer this theory and have been working on a similar model that expands upon the work. While I am a long way from completing studies, I did use my model for my own n=1 C19 study.
Unlike the immune theory of disease, which focuses on the recognition and response to pathogens specifically, the danger theory proposes that the immune system is activated by signals of danger, rather than the presence of a specific pathogen.
Danger theory suggests that the immune system recognises and responds to danger signals that are released by damaged or stressed cells, rather than relying solely on the recognition of foreign pathogens. These danger signals, which can include molecules such as heat shock proteins, may be produced in response to a variety of stressors, including physical trauma, infection, or exposure to toxins.
According to the danger theory, the immune system responds to these danger signals by initiating an inflammatory response, which can help to clear damaged tissue and promote tissue repair. This response is not specific to a particular pathogen or type of danger signal but is rather a general response to cellular damage or stress. This model better explains so called auto-immunity (more on this in a future post).
Danger theory has gained significant attention in recent years as scientists seek to better understand the role of the immune system in a range of diseases, including cancer, autoimmune disorders, and chronic inflammatory diseases. While it is still an active area of research and debate, danger theory has helped to expand our understanding of the complex mechanisms that govern the immune response.
What fuels are used by the immune system?
An important part of my model (proportional danger theory) was understanding how the immune system uses a variety of different fuels to support its various functions, including:
Glucose: Glucose is the primary fuel source for immune cells. Glucose is obtained from the diet and is transported to immune cells through the bloodstream. Glucose is used by immune cells to generate ATP (adenosine triphosphate), which is the primary energy source for cellular metabolism.
Amino acids: Amino acids are the building blocks of proteins, which are essential for the growth and function of immune cells. Immune cells use amino acids to synthesise proteins and other important molecules.
Fatty acids: Fatty acids are a source of energy for immune cells, and are also used to build cell membranes and produce signalling molecules. Omega-3 fatty acids, in particular, have been shown to have anti-inflammatory effects and may help to support the immune system. This is likely an effect in which they balance out Omega-6 ratios and simply eating less PUFA would reduce inflammation.
Vitamins and minerals: Vitamins and minerals are essential for many of the metabolic processes involved in immune cell function. For example, vitamin C is necessary for the synthesis of collagen, which is an important component of connective tissue, while zinc is required for the development and function of immune cells.
Overall, the immune system requires a diverse array of nutrients to function properly, and a balanced and varied diet is essential for supporting optimal immune function.
Does the thymus play a part in immunity?
The thymus plays a critical role in the development and maturation of immune cells, particularly T cells. T cells are a type of white blood cell that plays a key role in the adaptive immune response, which is the immune system's specific response to pathogens.
The thymus is a gland located in the chest, just behind the breastbone. It is most active during childhood and adolescence, and begins to shrink in size and activity during adulthood. Within the thymus, immature T cells undergo a process called thymic selection, which helps to ensure that T cells are able to recognise and respond to pathogens, but are not activated by the body's own cells and tissues.
During thymic selection, immature T cells are exposed to a variety of proteins and other molecules that are expressed by cells in the body. T cells that recognise these self-proteins too strongly are eliminated, while T cells that recognise foreign pathogens are allowed to mature and leave the thymus to populate the rest of the body.
The thymus also plays a role in the development of regulatory T cells, which are a subset of T cells that help to prevent the immune system from attacking the body's own cells and tissues. Regulatory T cells are important for preventing autoimmune diseases, in which the immune system attacks healthy tissues and organs.
Overall, the thymus is an essential organ for the development and maturation of T cells, which are critical for the adaptive immune response and for maintaining immune tolerance.
PUFA causes thymus atrophy
There is some evidence to suggest that high levels of polyunsaturated fatty acids (PUFAs), particularly omega-6 PUFAs, may contribute to thymus atrophy in animals. However, the evidence in humans is less clear, more due to limited desire (financial) to conduct research, thus more research is needed to fully understand the effects of PUFAs on thymus function.
One study in rats found that a diet high in omega-6 PUFAs led to thymus atrophy and reduced T cell function, while a diet high in omega-3 PUFAs had the opposite effect, promoting thymus growth and T cell function. Other animal studies have produced similar findings.
In humans, some studies have suggested that high levels of omega-6 PUFAs may be associated with reduced thymus function, while others have not found a significant association. One study in healthy older adults found that higher levels of omega-6 PUFAs were associated with reduced thymus size and lower T cell function, while another study in children found no significant association between omega-6 PUFA intake and thymus function.
Was Sudden Infant Death syndrome initially blamed on what was believed to be an enlarged thymus
In the past, Sudden Infant Death Syndrome (SIDS) was thought to be caused by an enlarged thymus gland. The thymus gland is largest in infants and young children and gradually shrinks as the child grows older. At the time we were simply “following the science” and “trusting the experts”.
In the early 1900s, it was believed that an enlarged thymus gland could cause compression of the airway, leading to sudden death in infants. This theory was based on observations of infants who had died suddenly and had an enlarged thymus gland on autopsy.
However, subsequent research has shown that thymic enlargement is a common finding in infants and is not necessarily associated with SIDS. In fact, we shouldn’t really even call it thyme enlargement, and should classify it as normal healthy thymus size and realise that in those deceased due to disease (even in children), the thymus will typically be atrophied.
PUFA blocks cytochrome c oxidase and decreases cellular ATP production, thus inhibiting energy available for immune responses.
Yes, there is some evidence to suggest that high levels of polyunsaturated fatty acids (PUFAs), particularly omega-6 PUFAs, may interfere with cellular energy production by blocking the activity of cytochrome c oxidase, a critical enzyme involved in the electron transport chain that generates ATP, the primary energy currency of the cell.
Research has shown that PUFA-rich diets can lead to a decrease in the activity of cytochrome c oxidase, reducing ATP production in the cell. This effect may be particularly pronounced in the brain, which has high energy requirements and is particularly sensitive to changes in energy metabolism.
While some studies have suggested that high levels of omega-6 PUFAs may have negative effects on cellular energy production, it's important to note that not all PUFAs are created equal, and some types of omega-3 PUFAs, such as EPA and DHA, “may” have differing effects on cellular energy metabolism and brain function. As with all nutrients, those which are industrially produced, such as seed (vegetable) oils seemingly have the worst effects upon health outcomes.
How much ATP can humans produce?
The amount of ATP (adenosine triphosphate) that humans can produce varies depending on various factors such as age, sex, body size, and activity level. On average, a healthy human adult can produce approximately 50-75 kg of ATP per day, which is equivalent to the body weight of an average person.
The process of ATP production occurs through cellular respiration, which involves the breakdown of nutrients such as glucose, fatty acids, and amino acids to release energy. The energy is then used to generate ATP through a series of chemical reactions that occur in the mitochondria, which are the energy-producing organelles of the cell.
During aerobic respiration, which occurs in the presence of oxygen, a single molecule of glucose can produce up to 36 molecules of ATP. However, the amount of ATP produced during anaerobic respiration, which occurs in the absence of oxygen, is much lower, typically producing only 2 molecules of ATP per molecule of glucose. Hence we don’t favour breathless exercise in a pandemic for our daily hour of exercise.
Overall, the amount of ATP produced by the human body is an important determinant of energy availability and can vary depending on a range of factors. However, a healthy and balanced diet, regular exercise, and good sleep routine can all help to optimise ATP production and support overall health and well-being.
Can humans produce 36 molecules of ATP from a molecule of glucose if Cytochrome C oxidase in blocked by PUFA? Did “Eat Out To Help Out” potentially compromise a nations immunity?
No, if cytochrome c oxidase, a critical enzyme in the electron transport chain that generates ATP, is blocked by polyunsaturated fatty acids (PUFAs), the production of ATP from glucose will be significantly reduced regardless of the number of glucose molecules that are available.
Cytochrome c oxidase is the final enzyme in the electron transport chain, and its function is essential for the production of ATP via oxidative phosphorylation. When cytochrome c oxidase is blocked, the electrons cannot be passed along the electron transport chain, leading to a buildup of electrons and a decrease in the proton gradient across the mitochondrial “membrane”. As a result, the production of ATP is reduced or even halted. Not good for energy (think long covid symptoms) or immunity (think recurrent infections).
While some studies suggest that high levels of PUFAs may interfere with the activity of cytochrome c oxidase and decrease ATP production in the cell, it is important to note that blocking this enzyme completely would result in a significant reduction in ATP production, regardless of the amount of glucose available. It is also worth noting that the effects of PUFAs on energy metabolism are complex and are influenced by a range of factors, including the type and amount of PUFAs consumed, as well as other dietary and lifestyle factors.
If cytochrome c oxidase is blocked, it will prevent the transfer of electrons from cytochrome c to molecular oxygen (O2), which is the final step in the electron transport chain (ETC). As a result, there will be a buildup of reduced electron carriers, such as NADH and FADH2, in the mitochondrial matrix.
The buildup of these electron carriers can lead to an increase in the production of ATP through substrate-level phosphorylation, which occurs in the citric acid cycle (also known as the Krebs cycle) and glycolysis. However, the amount of ATP produced through substrate-level phosphorylation is relatively small compared to the amount produced through oxidative phosphorylation, which occurs in the ETC.
Therefore, in the absence of cytochrome c oxidase, the net production of ATP would be significantly reduced, as most of the energy derived from the electron carriers would not be harnessed in the form of ATP. The exact amount of ATP that would be produced in this scenario would depend on various factors, such as the availability of substrates and the metabolic state of the cell.
It is difficult to provide an exact number for the amount of ATP produced in the absence of cytochrome c oxidase, as it depends on various factors such as the type of cell, the availability of substrates, and the metabolic state of the cell. However, it is generally accepted that the majority of ATP production in aerobic respiration comes from oxidative phosphorylation in the electron transport chain, and the absence of cytochrome c oxidase would significantly reduce the amount of ATP produced.
In general, it is estimated that oxidative phosphorylation in the electron transport chain produces around 32-34 ATP molecules per glucose molecule, while substrate-level phosphorylation (which occurs in the citric acid cycle and glycolysis) produces only a small amount of ATP, typically 2-4 ATP molecules per glucose molecule. Without cytochrome c oxidase, the amount of ATP produced would likely be much closer to the small amount of ATP produced through substrate-level phosphorylation, rather than the much larger amount produced through oxidative phosphorylation. Therefore, it is likely that the amount of ATP produced in the absence of cytochrome c oxidase would be significantly reduced compared to normal aerobic respiration.
