Humans are constantly surrounded by pathogens— disease-causing organisms such as bacterium, virus, parasite, or fungus— whether in the environment or within our bodies. Susceptible individuals who encounter harmful pathogens are at risk of developing life-threating diseases. Fortunately, the body is readily equipped with an immune system— a system capable of developing a series of protective defenses against pathogens as a natural response.
Immune System Mechanisms
There are two main parts to the immune system, namely the innate and adaptive immune system (Johns Hopkins Medicine, 2022). The innate immune system is an inborn rapid response system that includes physical barriers such as the skin, cornea, and mucous membrane lining in the respiratory, gastrointestinal, and genitourinary tract. The epidermis is composed of many layers of closely packed keratinized cells to prevent pathogens from entering the body in the first place. Mucous membrane secretes mucus, a sticky fluid that traps invading pathogens and dust. The protective physical barrier formed by mucus prevents pathogens from reaching the surface of the epithelium Other barriers such as tears, saliva, and urine contain lysozyme, a lytic enzyme that also functions as a cationic protein. Lysozyme kills bacteria by lysing bacterial cell well, peptidoglycan, to disrupt bacterial membrane and then activate autolytic enzymes in the bacterial cell for destruction (Ganz, 2006). Exposure to harmful germs, parasites, and cells do not result in immediate sickness because of these physical barriers. Should the pathogen infect the body, however, the system will recognize, then employ phagocytes such as neutrophils and macrophages to surround, cover, kill, and neutralize the invader immediately. Phagocytes find invading pathogens by causing inflammation, a sign of tissue injury cause by external trauma or infection. Upon tissue injury, mast cells will give out signaling molecules such as histamine, causing nearby capillaries to dilate. Neutrophils and monocytes will then migrate to the infected area through the widened capillary to conduct phagocytosis and prepare for tissue healing. If cells still get infected, interferon will be secreted. Interferon is an antiviral factor that “interferes” with viral replication to prevent further spreading (Kopitar-Jerala, 2017). Pathogens may also directly activate complement, a system of plasma proteins that “complements” the process of inflammation and phagocytosis. Although the body can provide a series of rapid innate immune responses, infections are not always cleared. In such cases, the acquired immune system will continue the body’s response.
The acquired immune system (with help from the innate immune system) creates antigen-specific antibodies to protect the body from a specific invader (National Center for Immunization and Respiratory Diseases, 2021). Each pathogen is composed of a several subparts unique to its molecular structure. The subpart of a pathogen that helps the immune system form antibodies is called an antigen. Macrophages swallow up and digest pathogens but leaves behind and presents the antigen part for lymphocytes to recognize then attack. When an antigen is detected, B-immune system responds by stimulating B-lymphocytes to produce antibodies to attack leftover pieces of the pathogen. While the B-lymphocytes directly attack pathogens using antibodies, T-lymphocytes attack pathogen-infected body cells. The human body is comprised of over a thousand antibodies, but each antibody is programmed to recognize only one specific antigen. After creating antigen-specific antibodies as a primary response, the immune system also produces antibody-producing memory B and T cells. Memory cells remain alive even after the antibodies have defeated a specific pathogen. The immune system takes time (up to several days) to produce antigen-specific antibodies during the body’s first encounter against a pathogen, but memory cells can recognize and directly produce specific antibodies to defend against it. Thus, the immune system will be able to respond rapidly if the body is exposed to the same antigen more than once in the future. By working together collaboratively and effectively in producing antigen-specific antibodies, natural immunity against a specific disease is achieved. Check the video below to learn how the immune system works using visuals:
Vaccine-induced Immunity
Immunity to a specific disease is achieved through the presence of antigen-specific antibodies, but only lasts for a certain time period. Although a newborn baby may acquire passive immunity (given antibodies) from its mother through the placenta, only active immunity (produce antibodies) is long-lasting or even life-long. Active immunity can be further categorized into two types, namely natural and vaccine-induced. According to the Division of Viral Diseases at the National Center for Immunization and Respiratory Diseases (2022), immunizations train the immune system to create antibodies as a form of protection against harmful diseases through vaccination. Vaccines are harmless variants of a pathogen used to stimulate the immune system to defend the body against specific pathogens and thereby, prevent specific diseases. Instead of containing the antigen itself, vaccines contain the blueprint for producing antigens. For numerous viral diseases such as measles and polio, prevention by vaccination is the only medical method to prevent illness.
Different types of vaccines may be made from different materials, but all types help protect the body against life-threatening diseases by stimulating the production of antigen-specific antibodies. For instance, mRNA Covid-19 vaccines contain material from SARS-Cov-2 (Covid-19-causing virus), protein subunit Covid-19 vaccines include harmless proteins from SARS-Cov-2, while vector vaccines contain viral vectors of SARS-Cov-2. All three of these materials are different, but all prompt the immune system to build B-lymphocytes and T-lymphocytes to fight a specific pathogen (in this case, SARS-Cov-2) if the body ever gets infected in the future. Several vaccines require multiple doses, given months or years apart to allow the production of long-lived antibodies and development of memory cells. Vaccines safely enable individuals to achieve immunity against a certain disease without having to be infected beforehand due to programmed memory. Vaccinated individuals are provided partial protection from infection, and protection from severe symptoms even if infection does occur as the body has prior experience in “fighting the same opponent”.
However, not every individual can be vaccinated. Those with underlying health conditions that weaken their immune systems (e.g. cancer, HIV) or allergies to specific vaccine components are unable to receive certain vaccines. Fortunately, they can still be protected if they live amongst others who are vaccinated— in a community with herd immunity (World Health Organization, 2020). Should the majority of people living in a community be vaccinated, the pathogen will be unable to circulate easily. Therefore, eligible individuals are highly advised to vaccinate themselves against life-threatening viral diseases, to protect themselves and others.
Impact of Lifestyle Factors on Immunity
Based on previous research done by Marsland et al. (2002) and Madison et al. (2021), psychological stress is known to affect immune function and vaccine efficacy. Individuals (even young and healthy students) who experienced significant stress and anxiety for a short period of time before getting vaccinated took a longer time to develop antibodies against hepatitis B, influenza, and pneumonia (Madison et al., 2021; Migala, 2021). Stressed individuals also experienced more side effects (e.g. fatigue and low mood) and reduced duration of immunity following a vaccine. According to Madison et al. (2021), stress and mental health conditions may lead to neuroendocrine or inflammatory changes that negatively alter vaccine efficacy, thereby necessitating a more frequent booster vaccination. Moreover, stressed and/or depressed individuals are more likely to perform unhealthy lifestyle habits, including lack of sleep, improper nutrition, and irregular exercise— all of which are factors that negatively affect antibody response following immunization.
Spiegel (2002) previously reported that short-term sleep deprivation prior to vaccination negatively impacts antibody count and thereby, efficacy of vaccines by lowering antibody count. More specifically, restricted sleep (< 4 hours) resulted in a >50% decrease of antibody production in response to influenza immunization. Sleep helps activate cytokine (IL-12 and IFN-γ) expression to regulate anti-viral immune defence mechanisms (Irwin, 2019). Sleep may also boost the number of antigen-presenting cells and T-lymphocytes (CD4+) (Lange et al., 2019), improving immunological memory formation. Meanwhile, sleep deprivation (<6 hours) results in decreased lymphocyte proliferation and innate immune cell activity against tumour and virus-infected cells by reducing up to 72% of natural killer cell activity (Frel et al., 2020). In other words, sleep plays a significant role in decreasing vulnerability and susceptibility to viral infection.
Childs et al. (2019) also demonstrated that adequate and appropriate nutrition is required for optimal immune function. Proper nutrition allows immune cells to initiate effective responses against pathogens as well as resolve unnecessary responses to avoid any underlying chronic inflammation (e.g. redness, swelling, feeling of heat and pain). For instance, micronutrients vitamin A and zinc regulate cell division to boost proliferative responses within the immune system, while the amino acid arginine helps macrophages generate nitric oxide to kill tumor cells while exerting anti-inflammatory effects (Childs et al., 2019). While undernutrition impairs immune function due to specific unmaintained roles in the immune system, overnutrition negatively alters leukocyte (including lymphocytes) count and cell-mediated immune responses. Overnutrition leads to obesity, which then results in immunodeficiency. Obesity-associated lipid build-up increases leptin (pro-inflammatory) and decreases adiponectin (anti-inflammatory) production, inducing chronic inflammation as an immune response (Heredia et al., 2012). Furthermore, obesity may result in insulin and leptin resistance, adipose tissue expansion, as well as decreased pancreas β-cell function, all of which limit metabolic responses to immunity challenges through the development of comorbidities such as Type 2 diabetes, cardiovascular diseases, hypertension, and cancer (Hardy et al., 2012; Kasuga, 2006). According to Mohammad et al. (2021), these changes negatively impair immune cell growth and proliferation, host immune defense, and glucose metabolism. Expanded ACE-2 adipose tissue could also spread infectious diseases such as Covid-19 to other tissues, increasing severity of disease. Thus, chronic inflammation and metabolic dysfunction caused by both undernutrition and overnutrition dysregulate innate immune system mechanisms, resulting in an increased risk of infectious disease susceptibility, severity, and mortality.
Additionally, Silveira et al. (2021) suggests that regular moderate-intensity physical exercise (at least 150 minutes every week) strengthens the immune system by modulating cellular immunity. During and after physical exercise, pro- and anti-inflammatory cytokines are released, while lymphocyte recruitment and circulation is increased. Such changes are associated with the reduction of excessive weight, increased physical and cardiopulmonary conditioning, optimal pro-inflammatory and pro-thrombotic states, decreased oxidative stress, and improved glycemic, insulinic, and lipidic metabolisms. Similar to the impact of optimal nutrition, regular physical exercise prevents obesity, and positively impacts all the factors that would be negatively altered by obesity. Therefore, the practice of regular physical exercise may help lower the risk of viral infections, as well as the intensity of severe symptoms and incidence of mortality caused by infections.
