THE FUNDAMENTALS OF PSYCHONEUROIMMUNOLOGY AND THE CURRENT PANDEMIC

“Men ought to know that from the brain, and from the brain only, arise our pleasures, joy, laughter, and jests, as well as our sorrows, pains, griefs, and tears.” ~Hippocrates

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By Sajal P. and Sacheth K.D.

INTRODUCTION TO PSYCHONEUROIMMUNOLOGY

Psychoneuroimmunology is a discipline of science which deals with the interconnections between an individual’s psyche (state of mind), nervous system, and immune system. In other words, it investigates how mental health and psychological well-being can facilitate better management of physical disease and thereby the whole path to recovery. Although we do know that our immune system has attained strong and efficient ways to fight disease through complex evolutionary processes over time, it is still highly dependent on our central nervous system. The immune system depends on our central nervous system for signaling processes that eventually allow it to take immune action against pathogens. This clearly indicates that our psychological states impact the way we defend ourselves from disease. A meta-analysis conducted in 2004 by Segerstrom and Miller indicated that exposure to chronic stressors suppressed both cell-mediated and humoral immune responses. In other words, a wide range of research reveals the fact that stress inhibits our ability to form antibodies and fight diseases.

THE POWER OF YOUR MIND!

According to recent research, the brain regulates how our bodies respond to the threat of bacterial infections. It accomplishes this by the output of PCTR1 (protectin conjugate in tissue regeneration 1), a defensive molecule that aids white blood cells in killing invading bacteria. Researchers have discovered that severing the right vagus nerve in mice impairs their ability to clear E. coli infections significantly. A neurotransmitter called acetylcholine is released by the nerve, which instructs another form of immune cell (innate lymphoid cells) to increase PCTR1 output. As a result, macrophages’ ability to locate and destroy bacteria is controlled. PCTR1 belongs to a class of molecules known as specialized pro-resolving mediators, which regulate how our bodies respond to inflammation. White blood cells make it from docosahexaenoic acid, an essential fatty acid derived from fish oil.

Your brain creates chemicals that can help you live a healthier life. Endorphins, which are natural painkillers, and gamma globulin, which enhances the immune system, are two of these substances. According to research, the brain’s output is influenced by emotions, feelings, and aspirations. When you are sick but have hope and a good outlook and believe that you’ll get better, your brain is more likely to generate chemicals that help your body recover.

Studies have shown laughter to lower stress hormones, raise “healthy” cholesterol, and minimize artery inflammation. People who pictured themselves working out were able to achieve 24 percent more muscle strength, according to one report. While people who lifted weights showed better results, the research indicates that mental exercise can lead to significant changes in muscle mass. According to studies people who believe their lives are important are more likely to live happier, longer lives. Gratitude has been related to improved sleep quality and duration in studies. Numerous studies have shown that the placebo effect has an impact on treatment efficacy. Your confidence in the efficacy of such treatments could be more powerful than the treatment itself.

The Psychoneuroimmunological Link to HIV and Cancer Progression

HIV stands for Human Immunodeficiency Virus. It kills an essential type of immune cell (called CD4 cells or T cells) that helps protect you from infections over time. AIDS is a disorder caused by HIV’s destruction of the immune system. When you contract harmful diseases or have a reduced number of CD4 cells, you have AIDS.

Why do some people who test HIV positive do not test positive for AIDS?

Some psychological states have been linked to AIDS progression, while others have been linked to improved immunity and survival, according to PNI studies. The degree of fatalism about HIV, the degree and length of stress, grief, or depression, knowledge of life purpose and goals, and self-assertive capacity are all factors that influence these states. Fatalistic assumptions about HIV status have been linked to poor health outcomes. Study participants who were both fatalistic and newly bereaved had the shortest survival rates. Further research discovered that fatalistic thought and bereavement changed immune markers related to AID progression. The research found that more combined life stress and less cumulative social support increased the risk of developing AIDS by two to three times (Leserman et al., 1999). An increased measure of pessimism was linked to lower NK-cell cytotoxicity in a group of HIV-positive black women at risk for cervical cancer in a study by Byrnes et al. (1998).

Cancer is caused when abnormal or damaged cells of the body start growing uncontrollably and spread to other parts of the body. Distress or depression is linked to two essential carcinogenesis processes: weaker DNA repair and alterations in apoptosis. Helplessness and repression appear to be associated with a poor prognosis, while denial/minimizing appears to be associated with a good prognosis. A poor prognosis is predicted by having undergone loss incidents, having a low degree of social support, and having persistent depression. There may be many reasons for the apparent correlation between psychological stress and cancer. People who are stressed, for example, can develop habits that increase their risk of cancer, such as smoking, overeating, or consuming alcohol. In some studies, the stress hormone norepinephrine, which is part of the body’s fight-or-flight response mechanism, has been found to encourage angiogenesis and metastasis.

THE IMMUNE SYSTEM

Immunity is the overall ability of an organism to fight and ward off disease-causing organisms with the help of the immune system. Immunity can be of 2 types- Innate immunity and Acquired immunity.

Innate immunity is nonspecific and is present from birth. It provides a first-level response to any external disease-causing organisms. The innate immune system utilizes certain cells in the form of cellular barriers like neutrophils, basophils, eosinophils, natural killer cells, macrophages, and monocytes along with the help of physical (skin and epithelial linings in body tracts), physiological (saliva, tears, etc), and cytokine barriers. The innate immune system recognizes foreign organisms with the help of pattern recognition receptors that detect molecular patterns present in pathogens but not in normal cells. Such detection also alerts the adaptive immune system and thus facilitates the mobilization of respective antibodies to the infection site. The pathogen-infected cells release specific proteins called interferons which signal the adaptive immune system to invite a more strong and effective immune response. The other cells mentioned above play their part by detecting and phagocytosing (engulfing) pathogenic material.

Acquired immunity is the second level of immune response characterized by the memory of past information and specialized cells called B cells and T cells. The B cells produce antibodies that bind to and destroy the pathogen. The T cells help the B cells to produce antibodies and they themselves fight against the pathogen. The T cells are majorly of 2 types, i.e, the Helper T cells and the Cytotoxic T cells.

The Helper T cells are also called CD4+ T cells. They are known to help in the maturation of other immune cells or lymphocytes like the B cells. They are called CD4 T cells as they consist of a glycoprotein called CD4 on their surfaces. CD4+ T cells are activated when their receptor comes in contact with an antigen-presenting cell. Once this sensing happens, the CD4+ T cells produce cytokines to invite a stronger immune response and signal the other immune cells.

The cytotoxic T cells are also called CD8 T cells. These cells directly destroy the virus-infected cells or tumor cells once their receptors are activated by the antigen-presenting cells.

B cells produce different types of antibodies namely IgA, IgD, IgE, IgG, and IgM. Typically, antibody molecules consist of 4 polypeptide chains that make up the antigen-binding sites. Once the antigen binds to these sites, they are neutralized.

IgM is the first class of antibodies produced by the B cells. It consists of μ heavy chains, although many B cells eventually switch to making other classes of antibodies. This antibody plays a vital role in the initial response to infection.

IgG is the most common and the largest family of antibodies in the human body. They are known to be a major part of humoral immunity. They help by agglutinating and neutralizing pathogenic particles effectively. IgG is the only type of antibody that can be passed through the placenta.

There are memory B cells and memory T cells that are known to have information about previous exposure to the same pathogen. This memory helps in the faster production and effect of antibodies thereby significantly reducing the severity of later infections. The B and T cells are produced in special organs called lymphoid organs like bone marrow, thymus, spleen, etc. where they originate, mature, and proliferate into fully developed immune cells.

Stabilization/destabilization of antigens has been demonstrated to influence immunogenicity and immune polarization. For any given protein antigen there is a degree of stability, which leads to recognition and further production of antibodies against the same. Along with it the way an antigen unfolds itself determines the extent to which it is recognized by the Major Histocompatibility Complex of the antigen-presenting cells.

BRAIN ↔ IMMUNE SYSTEM INTERACTIONS

For the defense and homeostasis of the whole organism, the CNS and immune system tend to deal with complex signaling and feedback loops. IL1, which is formed by immune cells in the body as it fights infection, may have a significant impact on the brain, contributing to what researchers refer to as “sickness behavior.” Sickness behavior involves mood, memory, cognition, and sleep shifts, as well as activation of the HPA stress response.” In other words, when you’re ill, the immune system is informing your brain that you should rest.

The immune system is influenced by the brain’s endocrine and autonomic nervous systems. There are bidirectional neural mechanisms and psychological phenomena like stress and depression that may have an effect on the immune system. Acute stressors (lasting minutes) are associated with significant increases in nonspecific defenders (e.g., neutrophils, NK cells) in the bloodstream, antibody release into saliva, and increased development of cytokines that induce nonspecific immunity, all of which may be adaptive as part of the “fight or flight” response. Many of these changes are caused by sympathetic signaling via lymphocyte 2-adrenergic receptors. Shorter long-term stressors were linked to decreased cytotoxic lymphocyte activity, but antibody-producing functions remained largely unchanged. Long-term chronic stressors reduced the immune system’s cytotoxic and antibody-producing roles. The studies indicate that stress may reduce the protective immune response to a pathogen, resulting in an increased risk of morbidity and mortality, and thus using vaccines as a substitute for an infectious agent.

PSYCHOLOGICAL BASES OF AUTOIMMUNE DISEASES

The immune system misidentifies parts of your body, such as your joints or skin, as foreign in an autoimmune disorder. Autoantibodies are proteins released by the body that target healthy cells. Most common disorders involve Type 1 diabetes, Rheumatoid arthritis (RA), Psoriasis/psoriatic arthritis, Multiple sclerosis, Systemic lupus erythematosus (SLE), Addison’s disease, etc. Psychosocial stress can impair the body’s ability to regulate immune function, leading to the exaggerated responses seen in autoimmune diseases. According to a study, people who have been diagnosed with a stress-related condition are more likely to develop autoimmune disease and have a higher risk of autoimmune disease while they are younger.

CORONAVIRUS AND THE IMMUNE SYSTEM

Coronavirus is an RNA virus that results in an infection called COVID-19. The virus is spherical with around 60–140 nanometers in its diameter. The outer surface of the virus consists of proteinaceous projections called spike proteins. These proteins attach to the special receptors called ACE 2 receptors through which the viral genome enters into the host cell. Because the immediate innate immune response is weak, the virus easily propagates and reaches the respiratory tract where it encounters a strong innate immune response. By this time, the virus starts manifesting itself in the form of the already well-known COVID symptoms and becomes traceable through the testing of swab samples. At this point, cytokine proteins are released from coronavirus infected cells that signal adaptive immune response. The B cells reach the site and start producing antibodies that later prevent the entrance of the virus into new cells. The T cells help by killing virus-infected cells thereby preventing viral propagation and further infection. The T cells also use cytokines to invite a better and stronger response. In this way, the immune system takes over and completely destroys the virus inside our respiratory tracts. This whole process might take up to 6–8 weeks.

The COVID vaccines consist of inactivated/killed coronavirus particles. Once administered, they produce an immune response in the body. As a result antibodies against the SARS CoV2 will be generated in the body. Developing immunity in this way reduces the risk of getting the illness. The chances of fatality significantly reduce. It is important to note that the vaccine does not guarantee the prevention of infection, rather the severity is reduced notably. Vaccines protect individuals who are at a higher risk of infection.

Since viruses repeatedly multiply, they are at a higher chance of mutating their genome. These mutant viruses have a different way in which they affect people. Thus we can observe differences in symptomatology depending upon the variant that has led to the infection.

It is important to note that a strong and efficient immune system is a necessity for an easier and less severe recovery process from COVID-19. Thus a healthy psychoneurological immunity would be essential in helping us cope with the virus. Research conducted by Sung and Kuan suggests people take up certain steps for maintaining the same. They mentioned a healthy lifestyle, regular exercise, balanced nutrition, quality sleep, and a strong connection with people, all can help in the development of a prepared immune system in the form of psychoneurological immunity to combat the virus.

BIBLIOGRAPHY

• Dalli, J. (2017, January 5). How the brain helps the body fight bacteria. The Conversation. https://theconversation.com/how-the-brain-helps-the-body-fight-bacteria-70833
• Rasmussen HN, et al. (2009). Optimism and physical health: A meta-analytic review. Annals of Behavioral Medicine, 37(3): 239–256.
• Mind-body wellness. (n.d.). University of Michigan | Michigan Medicine. https://www.uofmhealth.org/health-library/mente
• 7 ways to heal your body by using the power of your mind, backed by science. (2016, October 24). Inc.com. https://www.inc.com/amy-morin/7-ways-to-heal-your-body-by-using-the-power-of-your-mind-backed-by-science.html
• Psychoneuroimmunology. (n.d.). ScienceDirect.com | Science, health and medical journals, full text articles and books. https://www.sciencedirect.com/topics/medicine-and-dentistry/psychoneuroimmunology
• Leiphart JM. Psychoneuroimmunology: a basis for HIV treatment. Focus. 1997 Feb;12(3):1–4. PMID: 11364257.
• Kiecolt-Glaser JK, Glaser R. Psychoneuroimmunology and cancer: fact or fiction? Eur J Cancer. 1999 Oct;35(11):1603–7. doi: 10.1016/s0959–8049(99)00197–5. PMID: 10673969.
• Garssen B. (2004). Psychological factors and cancer development: evidence after 30 years of research. Clinical psychology review, 24(3), 315–338. https://doi.org/10.1016/j.cpr.2004.01.002
• Watson, S. (n.d.). Autoimmune diseases: Types, symptoms, causes, diagnosis & more. Healthline. https://www.healthline.com/health/autoimmune-disorders#treatment
• Psychological Stress and Cancer. (2012, December 10). National Cancer Institute. https://www.cancer.gov/about-cancer/coping/feelings/stress-fact-sheet#:%7E:text=Apparent%20links%20between%20psychological%20stress,a%20person’s%20risk%20for%20cancer
• Shmerling, R. H. (2020, November 11). Autoimmune disease and stress: Is there a link? Harvard Health Blog. https://www.health.harvard.edu/blog/autoimmune-disease-and-stress-is-there-a-link-2018071114230#:~:text=A%20new%20study%20has%20raised,diagnosed%20with
• Segerstrom, S. C., & Miller, G. E. (2004). Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychological bulletin, 130(4), 601–630. https://doi.org/10.1037/0033-2909.130.4.601
• Psychoneuroimmunology and HIV disease progression. (1999, October 1). Psychiatric Times. https://www.psychiatrictimes.com/view/psychoneuroimmunology-and-hiv-disease-progression
• Innate immunity. (n.d.). ScienceDirect.com | Science, health and medical journals, full text articles and books. https://www.sciencedirect.com/topics/medicine-and-dentistry/innate-immunity#:~:text=Innate%20immunity%20is%20a%20rapid,by%20all%20plants%2
• (n.d.). NCERT. https://ncert.nic.in/ncerts/l/lebo108.pdf
• Novel coronavirus structure reveals targets for vaccines and treatments. (2020, March 10). National Institutes of Health (NIH). https://www.nih.gov/news-events/nih-research-matters/novel-coronavirus-structure-reveals-targets-vaccines-treatments#:~:text=Like%20other%20coronaviruses%2C%20SARS%2DCoV,fuse%20
• Immune response in COVID-19: A review. (n.d.). ScienceDirect.com | Science, health and medical journals, full text articles and books. https://www.sciencedirect.com/science/article/pii/S1876034120305670
• How do T lymphocytes work — Google search. (n.d.). Google. https://www.google.com/search?q=how+do+t+lymphocytes+work&oq=How+do+t+ly&aqs=chrome.0.0j69i57j0l8.4189j0j15&sourceid=chrome&ie=UTF-8
• Scheiblhofer, S., Laimer, J., Machado, Y., Weiss, R., & Thalhamer, J. (2017). Influence of protein fold stability on immunogenicity and its implications for vaccine design. Expert review of vaccines, 16(5), 479–489. https://doi.org/10.1080/14760584.2017.1306441
• Coronavirus disease (COVID-19): Vaccines. (n.d.). https://www.who.int/news-room/q-a-detail/coronavirus-disease-(covid-19)-vaccines#:~:text=The%20COVID%2D19%20vaccines,the%20virus%20if%20exposed
• Kim SW, Su KP. Using psychoneuroimmunity against COVID-19. Brain Behav Immun. 2020 Jul;87:4–5. doi: 10.1016/j.bbi.2020.03.025. Epub 2020 Mar 29. PMID: 32234338; PMCID: PMC7194899.