**1. Introduction**

A healthy immune system is beneficial for every organ. The self-regulation of T-cell, B-cell, and natural killer cell activity creates the immune system's homeostasis. The functioning immune systems serve as a connected network in the body, defending the organs against numerous immunological diseases. Additionally, it recognises invasive pathogens like bacteria, viruses, and parasites and reacts quickly to them [1]. The innate immune system and the adaptive immune system are the immune system's two main subsystems. The innate immune system responds in a programmed way to a wide range of immunologically active proteins and immune stimuli. In comparison, the adaptive immune system responds sequentially to each stimulus by identifying the chemicals the immune cells use to operate [2]. Immunological disorders, inflammatory reactions, and the development of cancer can all be brought on by the dysregulation of immune activities. Chronic immunodeficiency has also been linked to an increase in infections that can be fatal [3]. Genetic changes are also related to some immune illnesses. These severe immunological conditions include acquired immunodeficiency syndrome (AIDS) [4]. Type 1 diabetes, rheumatoid arthritis, Hashimoto's thyroiditis and systemic lupus erythematosus are just a few major autoimmune disorders that are commonly treated using immunomodulatory medications [5].

However, the excellent health of a patient with chronic immunological problems depends on a functioning immune system. Numerous organic substances, including polyphenols, alkaloids, polysaccharides, glycosides, lactones, terpenoids, and flavonoids, have been shown to modify immune cells and have immunomodulatory effects [6]. The essential immunological cells it interacts with are macrophages, dendritic cells, lymphocytes (T- and B-cells), and natural killer (NK) cells. The primary immunomodulatory effects are brought about by secreted antibodies against various pathogens and maintain immunological homeostasis [7]. Our bodies' immune systems create a selfdefence strategy to stave off illnesses from numerous pathogens. Innate and adaptive immune cells work with anatomical and physiological barriers to form the human body's three layers of protection against pathogens. Saliva, epidermis, mucous membranes, low stomach pH, and other secretions are among the anatomical and physiological barriers that make up the immune system's first line of defence against pathogens. Other bodily fluid discharges and the stomach's low pH level can also easily interact with immune cells [8]. The second level of defence begins with inflammatory cells like mast and macrophage cells and uses complement system formation and immunomodulatory action to establish innate immunity. It covers the roles of basophils, NK cells, mast cells, neutrophils, eosinophils, macrophages, dendritic cells, and natural killer T cells in immunological activity [9]. Twenty serum glycoproteins make up the complement system, where the main immunomodulatory effects begin. Additionally, three pathways—the lectin pathway (mannose-binding lectin reaction), the alternative pathway (bacterial endotoxin reaction), and the classical pathway (antigen–antibody reactions)—are involved in the activation of the complement system. Circulatory complement-3 (C3) proteins are involved in every pathway and are crucial for immunomodulatory effects [10]. Through T and B cells, the first and second levels of defence systems generate non-specific immune responses, known as adaptive immunity. This is an antigen–antibody-associated immune cell-specific response and forms the third level of the immune defence system [9]. The primary innate and adaptive immune system function and their cells are illustrated in **Figure 1**.

Pathogen recognition receptors (PRRs) are used in the innate immune system to identify the infection pattern. Pathogen-associated molecular patterns (PAMPs) detect the microbial components of molecular proteins. The PAMPs consists of bacterial parts such flagella, nucleic acid components, and lipopolysaccharide [7]. PPR families include cytoplasmic proteins like NOD-like receptors (NLRs), retinoic acidinducible gene-I-like receptors (RLRs), and transmembrane proteins like C-type lectin receptors (CLRs), and toll-like receptors (TLRs) [11]. Antigen-presenting cells, such as dendritic cells (DCs), B cells, and macrophages, make up non-specific immune systems. In order for cytotoxic T-cells and B-cells, as well as non-antigen specific macrophages, NK cells, and eosinophils, to perform their essential roles, dendritic cells must first deliver the antigens to a group of domain-4 (CD4)-T-helper cells. Tumour necrosis factor-α (TNF-α) and cytokines (IFN-γ) are generated during the proliferation of DCs as a result of immunological responses [12]. In adaptive immunity, a defence mechanism is formed by the injected agents against the particular pathogens and stop infections. It is also referred to as acquired immunity. It

*Perspective Chapter: Phytocompounds as Immunomodulators DOI: http://dx.doi.org/10.5772/intechopen.108858*

#### **Figure 1.**

*Immune system traits and functions of different innate and adaptive immune cells. There are two types of immunity in the immune system: Innate immunity and adaptive immunity. Among the participants in the innate immune system are dendritic cells, macrophages, mast cells, granulocytes (neutrophils, eosinophils and basophils), NK cells, NKT cells and δγ T cells. The pink grid lists each cell type's primary fuctions. B cells, CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells and other cells are all part of the adaptive immune system. Under various microenvironments specialised by interacting cytokines and chemokines, as well as unique activation of particular transcription factors, CD4+ T cells can develop into Th1,Th2,Th17 and inducible Treg (iTreg) cells. CD8<sup>+</sup> T cells are in charge of verifying cytotoxicity against cancerous or virus-infected cells. Treg cells are often divided into two types, natural Treg (nTreg) cells and iTreg cells. To maintain immunological homeostasis, they can control particular immune responses, including immune tolerance. Abbreviations: TCR,T cell receptor; MHC-II, major histocompatibility complex class II; NK, natural killer cells; NK T cells, natural killer T cells; Th1,T-helper type 1; Th2,T-helper type 2; Th17,T-helper type 17; IL-2, interleukin-2; IL-13, interleukin-13; IL-17, interleukin-17; IL-22, interleukin-22.*

primarily affects T and B cells, resulting in a cell-mediated immunological response and antibody generation. This adaptive immune response is primarily supported by CD4+ T-lymphocytes (helper T-cells) and CD8+ T-lymphocytes. Additionally, these T-helper cells are developed from Type-1 T helper (Th1) and Th2 cells, and they secrete IFN-γ and IL-5 to improve adaptive immune responses [13].

#### **1.1 Immunomodulators**

Immunomodulators include immunostimulants and immunosuppressive medications [14]. The efficient and effective homeostasis that the healthy immune system generates keeps the human body free from disease. Additionally, it governs the cellular signalling molecules as the favourable host responses and has strong communication of cells via signal transduction pathways. Immune cell-acting substances can either boost or inhibit immune cells' typical efficiency and function when administered endogenously or exogenously. It is sometimes referred to as host responses for immunomodulatory actions [15]. This immunity prevents chronic immunological disorders such as AIDS, cancer, autoimmune diseases, and allergic reactions [14].

Immunostimulants, immunoadjuvants, and immunosuppressants are the three categories that comes under immunomodulators. Immunostimulants are substances that cause the immune system's cells to become active. Vaccines operate according to these principles to enhance the specific immunostimulant actions. Immune response to specific pathogenic antigens is strengthened by it. Some reports have shown that natural substances, such as phytocompounds, are known to have general immunostimulant effects. Cancer and other chronic infections like those that cause immunodeficiency disorders are also said to be attenuated. Interferon-alpha (IFNalpha) and granulocyte colony-stimulating factors are two examples of endogenous immunostimulants involved in developing immunostimulant effects [16]. Moreover, FDA also describes the immunoadjuvants therapy category for immunological illnesses. The conjugation of immunoadjuvants with a vaccination antigen results in the augmentation and potentiation of target proteins for the particular immune response against the antigen. Histamine, tuftsin, interferons, IL-1, transfer factor, and IL-1 are endogenous natural adjuvants. It can intensify the targeted antigen's interactions with the host immune system and induce phagocytosis [17, 18].

To lessen overly strong immunological reactions, immunosuppressants are also necessary. Excessive immune cell function can cause serious systemic consequences. Immunosuppressive medications are necessary for various therapeutic situations, such as organ transplantation (pre and post-surgical conditions). A few immunosuppressive drugs momentarily weaken immune cell functions. Along with these conditions, it is also used to treat rheumatoid arthritis, myasthenia gravis, and Grave's disease. Additionally, it manages graft rejection reactions in tissue (skin) and cells (bone marrow transplant) [17]. Similarly, some natural phytoconstituents suppress the immune system and treat immunological diseases by interfering with the host cell's molecular communication pathways.

### **2. Phytocompounds as immunomodulators**

More than 5000 years of history are found for medications made from natural products, compared to a few hundred years for Western medicine. More than 85,000 plant species have been used medicinally around the world. According to the WHO, up

#### *Perspective Chapter: Phytocompounds as Immunomodulators DOI: http://dx.doi.org/10.5772/intechopen.108858*

to 80% of people worldwide, primarily in developing nations, rely on herbal remedies to cure a various illnesses, including immunological disorders [19]. Additionally, about 30% of all FDA-approved medications have a botanical origin [20]. Based on this data, it's critical to look into traditional phytomedicines' chemical makeup to assess their potential as immunomodulatory agents for immunological diseases. The chemical compositions, molecular targets, and related illnesses of the representative phytocompounds are summarised. The classification of phytochemicals is given in **Figure 2**.

Numerous pharmacological effects can be attributed to phytocompounds including immunomodulatory effects. Several phytoconstituents, including polyphenols like stilbenes, resveratrol, hydroxycinnamic acids, and curcumin; flavonoids like epigallocatechin gallate (EGCG) and quercetin; alkaloids like berberine (BBR), & colchicine; terpenoids like andrographolide, & oleanolic acid; polysaccharides like pectin [21, 22] are found to act on immune system. They modulate the activity of a variety of immune cells, including dendritic cells (DCs), lymphocytes, neutrophils, monocytes, macrophages, basophils, mast cells, eosinophils, and natural killer (NK) cells. It frequently controls phagocytic cells, including neutrophils, monocytes, macrophages, basophils, mast cells and eosinophils that secrete inflammatory mediators and natural killer (NK) cells [23].

It is evidenced experimentally that the phytocompounds alter a number of the molecular targets of the immune cell signalling mechanism. In immune cells, they also modify the release of soluble substances and these include transcription factors and interleukins (IL) such as IL-2, IL-4, IL-6, IL-12, IL-17 and immunoglobulins (Igs) [24]. The transcription factors nuclear factor-κB (NF-κB) and inhibitor κB (I-κB) are frequently used to control the activity of immune cells and have immunomodulatory effects. It also phosphorylates the c-Jun N-terminal kinases (JNK/Jun) pathways, degrades the inhibition of the NF-κB p65 subunit and I-κB, increases the levels of reduced glutathione (GSH) and superoxide dismutase (SOD) dependent on T-lymphocytes, and collaterally enhances immune responses through the expression

**Figure 2.** *Classification of phytochemicals.*

of TLR4 and upregulation of cytokine genes [25]. Additionally, different immune cells and their cell signals behave in varied ways based on the pathophysiological circumstances of various body systems. Therefore, a clear, precise mechanism and the unique activity of phytoconstituents on immune cells must be thoroughly studied [26]. The following sections have detailed the specifics of phytoconstituents for the immunomodulatory mechanism of action.
