Avocado Consumption and Immune Response: A Review on Ethiopian Context

Immune System: An Overview

The immune system protects the body against infections and other external and internal threats by utilizing three distinct layers, depending on the nature of the threat: physical (e.g., skin, epithelial lining of the gastrointestinal and respiratory tracts) and biochemical barriers (e.g., secretions, mucus, and gastric acid), numerous different immune cells (e.g., granulocytes, CD4 or CDS T and B cells), and antibodies (i.e., immunoglobulins).

The first line of defence is innate immunity, which combines physical and biochemical barriers with a non- specific, leukocyte-mediated cellular response to defend against pathogens. If the pathogen manages to avoid these innate defences, a more complex, adaptive, antigen- specific response is triggered, mediated by T and B lymphocytes, which produces antibodies to target and destroys the pathogen. The adaptive immune system involves an antigen-specific response mediated by T and B lymphocytes that is activated by exposure to pathogens; this works with the innate immune system to reduce the severity of infection. The complement system can work with both the innate and adaptive immune systems; i.e., immunity from serum antibodies produced by plasma cells; i.e., an immune response that does not involve antibodies, but responds to any cells that display aberrant the major histocompatibility complex (MHC) markers, such as cells invaded by pathogens (Figure 1) [8].

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Life-style factors affecting immune function: An overview

Immunological maturity is achieved by adolescence, and young adults should be well fortified against attack by pathogens [9]. Nevertheless, several lifestyle-related factors affect immune competence in healthy adults and increase their risk of infection (Figure 2). In particular, energy-dense, micronutrient-poor convenience foods combined with a sedentary lifestyle, leading to obesity, make less bioavailable the immune-competent nutrients, suboptimal immune response, and increased risk of infection [10]. However, prolonged and excessive exercise, over-training is also thought to impair immune function [11, 12, 13]. Pollution and cigarette smoking compromise immune function, particularly when combined with poor nutrition [14]. Chronic, psychological stress is another Dhar G. Avocado Consumption and Immune Response: A Review on Ethiopian Context. Med J Clin Trials Case Stud 2019, 3(S1): 000S1-0001.

factor that can impact immune function, suppressing cellular and humoral responses [15]. Alcohol consumption has variable effects on immunity; moderate amounts of polyphenol-rich alcoholic beverages potentially provide some immune protection, but excessive consumption can suppress many aspects of immune function and consequently increase the risk of infection [16]. Sleep is an important homeostatic regulator of immune function and plays a specific role in immunological memory [17].

There is a bidirectional interaction among nutrition, infection and immunity: the immune response is compromised when nutrition is poor, predisposing individuals to infections, and a poor nutritional state may be exacerbated by the immune response itself to an infection [18]. It is clear that optimal immuno- competence depends upon nutritional status [19]. The risk of infection is also influenced by gender, age, genetics, early programming, vaccination history, pathogen exposure, specific health conditions, and diseases.

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Immune-competent Nutrients present in Avocado and their role in Immune Response: An overview

The nutrients which support and stimulate the immune system are called “Immuno nutritional elements”. Adequate nutrition (macronutrients and micronutrients) Dhar G. Avocado Consumption and Immune Response: A Review on Ethiopian Context. Med J Clin Trials Case Stud 2019, 3(S1): 000S1-0001.

Vitamin C: Role of Vitamin C in innate Immunity: (i) as an effective antioxidant that protects against ROS( reactive oxygen species) and RNS( reactive nitrogen species) produced when pathogens are killed by immune cells [25, 26]. (ii) To regenerate other important antioxidants such as glutathione and vitamin E to their active state? [25]. (iii) To promote collagen synthesis, thereby supporting the integrity of epithelial barriers [14]. (iv) To stimulate production, function and movement of leukocytes (e.g., neutrophils, lymphocytes, phagocytes) [25, 26]. (v) To increase serum levels of complement proteins [26]. (vi)In antimicrobial and Natural Killer (NK) cell activities and chemotaxis [14]. (vii) To involve in apoptosis and clearance of spent neutrophils from sites of infection by macrophages [27]. Role of Vitamin C in adaptive Immunity: (i) to increase serum levels of antibodies [26, 27]. (ii) Lymphocyte differentiation and proliferation [14, 27]. Vitamin A: Role of Vitamin A in innate Immunity: (i) To maintain structural and functional integrity of mucosal cells in innate barriers (e.g., skin, respiratory tract, etc.) [26]. (ii) For normal functioning of innate immune cells (e.g., NIC cells, macrophages, neutrophils) [26]. Role of Vitamin A in adaptive Immunity: (i) for proper functioning of T and B lymphocytes, and to generate of antibody responses to antigen [26]. (ii) To involve in development and differentiation of Helper T cell-1(Th1) and Helper T cell-2 (Th2) cells and supports Th2 anti-inflammatory response [14]. Vitamin E: Role of Vitamin E in innate Immunity: (i) act as fat-soluble antioxidant [14]. (ii) To protect the integrity of cell membranes from damage caused by free radicals [26]. (iii) To enhance Interleukin- 2(IL-2) production and NK cell cytotoxic activity [10]. Role of Vitamin E in adaptive Immunity: (i) To enhance T cell-mediated functions and lymphocyte proliferation [14]. (ii) To optimize and enhance Th1 and suppresses Th2 response [14]. Vitamin B6: Role of VitaminB6 in innate Immunity: (i) to regulate inflammation [28]. (ii) cytokine production and NK cell activity [28]. Role of Vitamin B6 in adaptive Immunity: (i) for endogenous synthesis and metabolism of amino acids, the building blocks of cytokines and antibodies [26]. (ii) Lymphocyte proliferation, differentiation and maturation [26]. (iii) to maintain Th1 immune response [14]. (iv) antibody production[28]. Folate: Role of Folate in innate Immunity: (i) to maintain innate immunity (NK cells) [14]. Role of Folate in adaptive Immunity: (i) involved in cell-mediated immunity [28]. (ii) Important for sufficient antibody response to antigens [28] (iii) to support Th-1 mediated immune response [28]. Zinc: Role of Zinc in innate Immunity: (i) as an antioxidant to protect against ROS and RNS [25]. (ii) To modulate cytokine release and induces proliferation of CD8+ T cells [14]. (iii) To maintain skin and mucosal membrane integrity [14]. Role of Zinc in adaptive Immunity: (i) cellular growth and differentiation of immune cells that have a rapid differentiation and turnover [29]. (ii) Essential for intracellular binding of tyrosine kinase to T cell receptors, required for T lymphocyte development and activation [25]. (iii) To support Th1 response [14]. Iron: Role of Iron in innate Immunity: (i) to involve in regulation of cytokine production and action [14]. (ii) To form highly-toxic hydroxyl radicals, thus involved in the process of killing bacteria by neutrophils [14]. (iii) To generate of ROS that kill pathogens [26]. Role of Iron in adaptive Immunity: (i) important in the differentiation and proliferation of T lymphocytes [26]. (ii) Essential for cell differentiation and growth, component of enzymes critical for functioning of immune cells (e.g., ribonucleotide reductase involved in DNA synthesis) [14]. Copper: Role of Copper in innate Immunity: (i) act as a free-radical scavenger [21]. (ii) Having antimicrobial properties [26]. (iii) Accumulates at sites of inflammation, important for IL-2 production and response [28, 26]. (iv) Innate immune response to bacterial infections [26]. Role of Copper in adaptive Immunity: (i) support in T cell proliferation [28]. (ii) Antibody production and cellular immunity [30]. Selenium: Role of Selenium in innate Immunity: (i) essential for the function of selenium-dependent enzymes (selenoproteins) that can act as redox regulators and cellular antioxidants, potentially counteracting ROS [14, 26]. (ii) selenoproteins are important for the antioxidant host defence system affecting leukocyte and NK cell function [28]. Role of Selenium in adaptive Immunity: (i) involved in T lymphocyte proliferation Dhar G. Avocado Consumption and Immune Response: A Review on Ethiopian Context. Med J Clin Trials Case Stud 2019, 3(S1): 000S1-0001.

[21, 28], (ii) participating in the humoral system (e.g., immunoglobulin production) [28].

Avocado and Immune Response: Scientific Evidences

Avocado contains substantial amounts of bioactive compounds such as phytosterols, β-sitosterol. The β- sitosterol in avocado also has a special effect on immunity, contributing to the treatment of diseases such as cancer, HIV and infections. In relation to cancer, it works by suppressing carcinogenesis and in HIV by strengthening the immune system [31]. This compound enhances lymphocytes proliferation and natural killer cell activity, which inactivates invading microorganisms [32].

Avocado can help in absorption antioxidants. Most carotenoid-rich fruits and vegetables are low in lipids. It has been documented that eating carotenoids (antioxidants including lycopene and beta-carotene) with avocado or avocado oil increased their absorption, which is attributed primarily to the lipids present in avocado [33].

Oxidative stress can induce neuronal damages and modulate intracellular signalling, ultimately leading to neuronal death by apoptosis or necrosis. There is evidence for increased oxidative damage to macromolecules in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. The critical review results indicated that compounds in avocado are unique antioxidants, by suppressing radical generation, acting as effective neuropreventive agents [34].

Jaquelina and his colleagues (2013) reported that antimicrobial activity of avocado with the help of antimicrobial peptides (AMP) to control of pathogens [35]. Basic scientific research studies a systematic review and meta-analysis of the available high-quality randomized clinical trials indicated that 300 mg of avocado and soybean unsaponifiables (ASU; an extract prepared from avocado and soybean oil) per day (with or without glucosamine and chondroitin sulfate) appears to be beneficial for patients with hip or knee Osteoarthritis. This is indicating anti-inflammatory function of avocado [36].

According to Andriamanalijaona, et al. (2006), avocado and soybean unsaponifiables (ASU) exert a preventive action on the deleterious effects exerted by IL-

1beta in periodontal diseases [37]. California Hass avocados have the highest content of lutein among commonly eaten fruits, lipophilic extract of avocado can inhibit the growth of both androgen-dependent (LNCaP) and androgen-independent (PC-3) human prostate cancer cell lines in vitro. Incubation of PC-3 prostate cancer cells with the avocado extract led to G2/M cell cycle arrest accompanied by an increase in p27 protein expression [38].

Avocado extract selectively induced apoptosis in human oral cancer cell lines by modulation of reactive oxygen species [39]. In the same year, Castillo-Juarez et al. concluded that antibacterial activity of a methanolic avocado extract against Helicobacter pylori, a cause of gastritis implicated in the etiology of gastric cancer [40]. The facial skin is frequently subjected to ongoing oxidative and inflammatory damage by exposure to ultraviolet rays and visible radiation, which can be controlled by carotenoids. Avocado's highly bioavailable lutein and zeaxanthin (type of carotenoids) may help to protect the skin from damage from both UV and visible radiation [41].

Ethiopian Context

In Ethiopia, avocados are very popular to everybody irrespective of age, sex, socio-economic class. Ethiopians are preparing juice by mixing avocado with sugar and milk or water, usually served with “Vimto”(locally called, brand name may be different, made up of grapes juice mostly) and a slice of lemon. Beside this, multiple layered fruit juices (locally called Spris) made of avocados, mangoes, bananas, guavas, and papayas is one of the favourite for Ethiopians. Avocados are also used to make salads and with bread as sandwiches as well as consumed raw. But avocado farming and marketing is not that much organised throughout the country. Even, there is no specific database available related to avocado consumption in any part of Ethiopia. According to Ethiopia National Food Consumption Survey (2013), the proportion of diet contributed by Vitamin A rich fruits and vegetables among women of Gambella region and Southern region relatively higher than other part of the country; Amhara region is comparatively better position in children Vitamin A rich fruits and vegetables consumption. Not only regional, difference is there between urban and rural population consumption also. But overall Vitamin A rich fruits and vegetables consumption is very low throughout the country [42]. The researchers have already documented that tobacco use, Dhar G. Avocado Consumption and Immune Response: A Review on Ethiopian Context. Med J Clin Trials Case Stud 2019, 3(S1): 000S1-0001.

physical inactivity, unhealthy diet (low dietary diversity and faulty dietary practices), excessive alcohol use, as well as "Khat" consumption are widely prevalent in Ethiopia, those behaviours are antagonist for bioavailability of immune-competent nutrients (those life- style factors related to immune system have been already mentioned in this article) [43].