Understanding The Immune System
The immune system includes two closely related components—innate immunity and adaptive immunity (Chaplin 2010; Parkin 2001).
Innate Immune System
Innate immunity is the body’s first response to foreign and potentially harmful substances. It is ready to mobilize rapidly, and can nonspecifically attack particles that trigger an immune response (antigens) (Drake 2010; Chaplin 2010; Abbas 2009). Important components of the innate immune system include:
- Physical and chemical barriers, such as the skin and its secretions, the lining of the gastrointestinal and respiratory tracts, and stomach acid (Drake 2010; Abbas 2009; Storey 2008).
- Phagocytic white blood cells, immune cells (eg, neutrophils, macrophages, monocytes, and dendritic cells) that engulf and destroy invaders and activate the adaptive immune system (Chaplin 2010; Drake 2010).
- Natural killer cells or NK cells, specialized immune cells that act rapidly to destroy abnormal cells, especially tumor cells and virus-infected cells (Iannello 2013; Wang 2012; Chaplin 2010; Storey 2008; Abbas 2009).
- Acute-phase proteins are involved in both innate and adaptive immunity. Some acute-phase proteins, including C-reactive protein and fibrinogen, are useful clinical markers of inflammation (Jain 2011; Storey 2008; Abbas 2009; Du Clos 2004; Heidari 2012).
Adaptive Immune System
If the innate defense system does not eliminate the threat, the next level of defense is the adaptive immune system (Drake 2010; Abbas 2009), which responds specifically to individual antigens. The adaptive immune system includes antibody-mediated immunity and cell-mediated immunity (Delves 2014).
- Antibody-mediated immunity. In antibody-mediated immunity, immune cells known as B cells produce and secrete antibodies into the blood and other tissues. Antibodies recognize and bind to specific antigens that occur on the surface of bacteria, viruses, fungi, or allergens, (or in the case of autoimmune conditions, self-cells,) in order to eliminate them or tag them for destruction by other immune cells (Delves 2014; Drake 2010; Abbas 2009).
- Cell-mediated immunity. Cell-mediated immunity relies on T cells, and can be active against infected cells, as well as phagocytic cells that have already engulfed harmful micro-organisms (Rezzani 2014; Abbas 2009; Griffith 2015; Mitchell 2010; Drake 2010). The thymus gland, located in the chest behind the breastbone, is responsible for the production of mature T cells. Age-related atrophy of the thymus plays a major role in immune senescence (Rezzani 2014; Abbas 2009; Griffith 2015; Mitchell 2010). Three important T-cell types that participate in cell-mediated immunity are helper T cells, cytotoxic T cells, and regulatory T cells:
- Helper T cells. Helper T cells augment the function of other immune cells. They promote antibody production by B cells, and help other immune cells recognize and kill microbes and infected cells (Abbas 2009).
- Cytotoxic T cells. Like NK cells, cytotoxic T cells directly attack and destroy foreign, infected, and abnormal cells, including cancerous and non-self cells (Waterhouse 2006; Delves 2014; Drake 2010; Storey 2008).
- Regulatory T cells. Regulatory T cells generally control or terminate an immune response to a perceived invader, minimizing tissue damage and helping protect against conditions in which the immune system reacts excessively, such as autoimmune diseases and allergies (Delves 2014; Drake 2010; Dimeloe 2010; Storey 2008; Belkaid 2007).
Emerging research suggests regulatory T cells may play a role in immune senescence. Some types of regulatory T cells appear to accumulate with age and may weaken the immune response to pathogens or malignant cells. At the same time, it appears that numbers of other types of regulatory T cells remain the same or even decline (Jagger 2014). Furthermore, the function of regulatory T cells may change with age (Jagger 2014; Fessler 2013; Schmitt 2013). Thus, a balanced and properly functioning array of regulatory T cells appears to be necessary to avoid smoldering chronic inflammation while maintaining immune competence and protection against infections and cancer.
Overall, the impact of regulatory T cells in the context of immune senescence cannot be stated categorically, and may vary among individuals. For example, a person with a history of autoimmune disease could potentially benefit from increased regulatory T-cell numbers or activity, while someone prone to infections or cancer but without a history of autoimmune disease might benefit from decreased regulatory T-cell activity (Belkaid 2007; Jagger 2014; Fessler 2013).
Microbiota and Immunity
The approximately 30 trillion bacteria that inhabit our bodies are collectively referred to as the microbiota. Most of these bacteria colonize the gastrointestinal tract, where nearly 70% of the immune system resides (Maranduba 2015; Vickery 2011; Vighi 2008; Sender 2016).
Disruption in the balance of the intestinal microbiota can increase inflammation, lead to infection, and contribute to disease development (Duncan 2013). Antibiotics and other drugs, toxins, diet, and harmful microbes can disrupt the proper balance of the gut microbiota (Carding 2015; Modi 2014). Changes in the populations of gut microbes may also be associated with aging (Duncan 2013).
Compared with the diet of people living in less-developed countries, the typical Western diet tends to be lower in fiber and higher in fat and refined carbohydrates. These dietary differences influence the composition and function of gut microbes, which can in turn modify immune function (Graf 2015; Noverr 2004; Vieira 2014).
The immune-enhancing and life-prolonging effects of caloric restriction may be partially explained by alterations in the gut microbiota (Vieira 2014). Animal and clinical studies have shown that caloric restriction may increase beneficial microorganisms in the gut and decrease detrimental ones. Caloric restriction may also reduce the amount of immunity-provoking compounds (ie, antigens) taken up by the gut, reducing the stress on the immune system (Festi 2014; Simoes 2014; Oh 2016; Zhang 2013).
Clinical trials have shown probiotics can enhance immune function in the elderly, potentially reducing the frequency and severity of infectious diseases (Maijo 2014; Duncan 2013; Ibrahim 2010; Candore 2008). Probiotics are live microorganisms that, when ingested via food or supplements, benefit health by restoring or maintaining a favorable balance of the intestinal microbiota (Homayouni Rad 2013; Duncan 2013; Homayoni Rad 2016).
One randomized controlled trial that enrolled over 700 healthy volunteers showed a preparation containing probiotics (Lactobacillus plantarum, Lactobacillus rhamnosus, and Bifidobacterium lactis), lactoferrin, and prebiotics (non-digestible fibers that can serve as a food source for benefical gut bacteria) reduced the incidence of respiratory diseases during the cold season. The probiotic formulation reduced the number, severity, and duration of upper respiratory infections; improvements in bowel function were also observed (Pregliasco 2008). In another trial, the same probiotic blend, given with colostrum (antibody-rich “first milk,” produced in late pregnancy), reduced flu incidence compared with vaccination and with no treatment (Belcaro 2010). Another probiotic, Bacillus subtilis CU1, enhanced the immune response and reduced the frequency of respiratory infections in elderly study participants (Lefevre 2015).