Immunity, Inflammation and Disease: What the Physician Should Know

Review Article

Austin Immunol. 2023; 6(1): 1021.

Immunity, Inflammation and Disease: What the Physician Should Know

Elroy Patrick Weledji¹*; Eleanor Ngounou²

¹Department of surgery, Faculty of Health Sciences, University of Buea, Cameroon, W/Africa

²Department of Biomedical Sciences, Faculty of health Sciences, University of Buea, Cameroon, W/Africa

*Corresponding author: EP Weledji Livanda Kongo hill, lumpsum quarters, PO Box 126, Limbe, S.W. Region Cameroon. Tel: 237699922144 Email: elroypat@yahoo.co.uk

Received: October 31, 2023 Accepted: December 01, 2023 Published: December 08, 2023

Abstract

The immune response system contributes to the body’s defence against infection, toxic or allergenic substances and is concerned with the recognition of tumour cells. In responding to a challenge the immune system is able to distinguish the body’s own cells and components (self) via the major histocompatability complex (HLA-DR) class 1 from cells that are foreign (non-self). The abnormalities of the immune response is demonstrated in the immunodeficiency diseases (congenital and acquired), the hypersensitivity reactions that may be involved in producing autoimmune diseases and the switching-off of T cell function by cancer cells. The genetic regulations of the immune system have major implications in clinical medicine as to the understanding of autoimmune disease and the idiotypic network that militates against autoimmune response and excessive immune responses. The relationship between immune function and tumour cells is highly complex but crucial to the understanding of both tumour rejection and progression mechanisms. The improved knowledge of the immune system has expanded the role of immunotherapy and vaccine therapy in oncology. The article reviewed the essential immune mechanisms in health and disease, and the clinical implications.

Keywords: Antigen; Tumour; Immune response; Autoimmunity; Immunotherapy; Hypersensitivity

Introduction

The body’s first line of defence against the environment (innate immunity) comprises a layer of epithelial cells which line all external surfaces. Once, this has been breached, the roles of the immune system and inflammation is to limit the damage, eliminate the foreign substance and promote repair [1,2]. Antigens are substances that induce an immune response, and proteins are the most antigenic material, followed by carbohydrates and lipids which are weakly antigenic. A large molecule, such as protein, may have several different sites (epitopes) to which dissimilar clones of immunologically competent cells respond. Some foreign proteins possess epitopes similar to those on self- proteins, accounting for some cases of auto-immunity i.e. the environmental aetiology of autoimmune disease. Immunological tolerance, the state of specific unreactivity to the body’s own tissue is thought to be acquired during fetal life when the immune system has not reached immunological maturity. Therefore, the body does not mount significant antibodies against its own tissues. Nevertheless, clones of cells which can produce ‘autoantibody’ (‘forbidden clones’) are thought to be produced throughout life and are either suppressed by large amounts of ‘self’ antigen or by antigen-specific T suppressor cells. ‘Autoantibodies’ are produced to a wide variety of antigens in autoimmune disease. These autoantibodies may be organ-specific, e.g. intrinsic factor antibodies in pernicious anaemia, thyroid antibodies in Hashimoto’s disease, or non-organ specific, e.g. antinuclear factor in Systemic Lupus Erythematosus (SLE). Autoimmune disease states are thought to arise when this system of mopping up forbidden clones breaks down [3]. The body can react to an antigen by producing antibody (humoral immunity) or specific T lymphocytes (cellular immunity). Antibodies belong to the class of serum proteins known as immunoglobulins. The T lymphocytes can be directly cytotoxic (T cytotoxic cells), or may produce cytokines (T helper cells) which are short-lived ‘hormones’ that acts on other cells to enhance or suppress their activity. Interleukins (lymphocyte activating factors) are specific lymphokines active between cells of the immune system and affect antibody production. The role of complement- a multi-molecular activation system of plasma proteins dependent in part on the sequential activation of a series of proteolytic zymogens is to promote inflammation, phagocytosis of antigens and immune complexes by macrophages (opsonization), and, lysis when activation is at or near the surface of a target cell. Abnormalities of the immune response are seen in the immunodeficiency diseases and the hypersensitivity reactions. Immunodeficiency may be inherited or may occur as a result of infection or drug therapy. It includes defects in antibody production (hypo- or agammaglobinaemia, selective IgA deficiency), complement fixation (C1 esterase inhibitor(hereditary angioedema), C1q (discoid lupus erythematosus), C1q, C1r, C4 or C2 (immune complex vasculitis), C3 or C3b inhibitor (Kline-felter’s syndrome), C5, C6, C7 or C8 (recurrent Neisseria); T lymphocyte function, (thymic aplasia, purine nucleoside phosphorylase deficiency, ataxia telangiectasia, Wiskott-Aldrich syndrome, Bloom’s syndrome, Severe Combined Immunodeficiency (SCID)); and phagocyte functioning (Job’s syndrome, Chronic Granulomatous Disease (CGD), Chediak-Higashi syndrome, myeloperoxidase deficiency) [5]. Immunological priming can lead, on further exposure to antigen, to either secondary boosting of the immune response or to an excessive damaging inflammatory reaction (antibody and cellular immune response) termed hypersensitivity. The implications of the immune response in health and the inflammatory (hypersensitivity) reactions (type I- anaphylactic, type II- cytotoxic, type III- immune complex mediated, type IV-cell mediated/ delayed, type V- stimulating antibody, and type VI- antibody-dependent cell mediated cytotoxicity) in disease are discussed. The proliferation of normal cells is carefully regulated but tumour cells have undergone mutations which makes them capable of uncontrolled growth. The immunological mechanisms involved in cancer growth are highly complex and the understanding of the relationship between immune function and tumour cells is important [6].

The Immune System

The primary lymphoid organs include the bone marrow and the thymus. They create special immune system cells called lymphocytes. Secondary lymphoid organs include the lymph nodes, the spleen, the tonsils and Mucosally Associated Lymphoid Tissue (MALT) in the gut, pharynx, bronchi, breast tissue, genitourinary system and the salivary and lacrimal glands. Lymphoid organs appear early in gestation. The thymus appears first, producing cells at 8 weeks which become immunocompetent at 11 weeks. The total population of lymphoid tissue is completed by 16 weeks of gestation. The bone marrow gives rise to the cells of the blood (the haemopoietic system). Some of these cells are involved in the recognition of antigen and mounting of an immune response (lymphocytes), while others are involved in elimination (e.g. macrophages and granulocytes). The thymus is derived from the third and fourth pharyngeal pouches, thus giving it an epithelial framework. It becomes populated by T lymphoblasts produced in the bone marrow, matures in the thymus generating large numbers of specific T lymphocytes. Thymus output is essential during early life to establish immune competence and homeostasis but is dispensable thereafter [1,7]. The tissue cells of the mononuclear phagocyte system are derived from blood monocytes and constitute approximately 5% of the total number of leucocytes. They are large and possess a bean-shaped nucleus. They have abundant cytoplasm containing lysosomes, rough endoplasmic reticulum and other organelles, rendering them capable of division and longevity. Immunoglobulin (IgG, IgE) and complement (C3, C5) receptors on their cell surface allow them to bind immune complexes. They can be divided depending on their function into antigen presenting cells, macrophages, multinucleate giant cells and sinus-lining histiocytes. Within the immune system the Antigen Presenting Cells (APC) are of particular importance. They are involved in interactions between T cells and B cells as a result of their ability to bind antigen-antibody complexes on their surface. The presentation of partially degraded antigen-antibody complexes or free antigen to T and B lymphocytes is important in humoral immunity. Tissue histiocytes are related cells, pinocytotic and facultative phagocytes found in most organs, particularly lining sinusoidal spaces in the spleen, lymph node and liver Their engulfment and digestion of cell debris and foreign material is important in non-specific immunity [8-10].

Lymphocytes are distributed in all organs, tissues, interstitial fluids except the brain. Lymphocytes account for up to 45% of the circulating blood leucocytes. They are divided into T lymphocytes (thymus- derived T cells)-70% of total lymphocytes, B lymphocytes cells derived from the bursa of Fabricius (in birds)-20% of total, and ‘Null’ Cells (10% of total). T cells are mainly involved with cell mediated immunity whilst B cells are involved in humoral immunity. Immunological memory is carried by long-living T and B cells. The T lymphocytes migrate from the bone marrow to the thymus where they are processed by the thymic epithelial cell hormone, which transforms them into immunocompetent cells. They are activated to form ‘blast’ cells by specific antigens and non-specific mitogens such as Phytohaemoglutinin (PHA). The activation involves macrophages (antigen- presenting cells), which process and present the antigen to the lymphocytes. T lymphocytes live for months or years and are divided into subsets depending on their role in the immune response, either regulating antibody production through the secretion of interleukins ( T helper (TH ) or T suppressor cells (Ts), directly cytotoxic (T cytotoxic (Tc) or taking part in delayed hypersensitivity reactions (T delayed hypersensitivity cells (TD)). Following the T cell interaction with antigen in association with the HLA glycoprotein (the T cell receptor complex), non-specific lymphokines and interleukins are released which amplify the immunological response. For example many bacteria and protozoa can survive within phagocytic cells (macrophages).These cells may be activated by Macrophage-Activation Factor (MAF) from specifically sensitized T lymphocytes, causing release of intracellular lysosomal enzymes and destruction of the infecting agents. T lymphocytes are the most potent mediators of adaptive anti-tumour immune response. The T cell mediated immunity can be transferred by giving T cells to a genetically compatible individual. In addition, the transfer factor, a soluble extract of T cells, can transfer some T cell functions which is applied in immunotherapy for cancer or infection [1,2]. It is important to note that T cells have proteins on them that turn on an immune response for an example when an infection is present, and other proteins that turn it off. These are called checkpoint proteins because if T cells are active for too long, or react to things they shouldn’t, they can start to destroy healthy cells and tissues [11]. B lymphocytes are derived from the bone marrow, are thought to be processed in the fetal liver and spleen and the adult bone marrow in mammals, and live for days or weeks. Although B cells and T cells are fundamentally similar, they differ in their surface receptors and markers (Table 1). They use antigen receptors to recognize foreign material, and both undergo a first stage of proliferation in one organ while simultaneously inducing specificity through rearrangement of their antigen-receptor genes. They then undergo a second antigen- driven proliferation at another site, usually a secondary lymphoid organ. Finally, they produce a functional cell, B cells giving rise to immunoglobulin-secreting plasma cells and T cells to functional cytotoxic T cells and helper T cells. Although antibody synthesis is inhibited by Ts cells, TH and B cell interaction is essential for an optimal humoral response to most antigens [1,2]. The Human Immunodeficiency Virus (HIV) is an RNA retrovirus that infects human T lymphocytes. The suppressed cellular immunity manifesting as the Acquired Immune Deficiency Syndrome (AIDS) allows the development of malignancies (Kaposi’s sarcoma, lymphoma) and opportunistic infections (pneumocystis jiroveci pneumonia, cryptosporidium, Cytomegalovirus (CMV), herpes simplex (SV), disseminated tuberculosis and candida 5-10 years later [12]. B cell and T cell hyperplasia are the basis of lymphomagenesis with T- cell lymphomas being clinico-pathologically more severe than B-cell lymphomas. The combination of recurrent plasmodium (P. falciparum) malaria and Epstein-Barr Virus (EBV) infection very early in childhood cause B cell hyperplasia which is an essential component of Burkitt’s lymphomagenesis. This EBV-associated lymphoma was one of the first tumours shown to have chromosomal translocation (chromosome 14) that activates an oncogene (c-MYC). The transformation of these cells compromises host defence and evolves mechanisms to escape immune surveillance. Thus, Burkitt’s lymphoma patients do not usually exhibit the B- symptoms (fever, night sweats, and weight loss) [13,14]. HIV-associated Burkitt’s lymphoma is associated with EBV in approximately 40% of cases [13]. T cell hyperplasia is mainly caused by infection with the Human T- Lymphotropic Retrovirus (HTLV-1) virus which may give rise to adult T-cell lymphoma/ leukaemia [15]. The ‘Null’ cells originate from the bone marrow but are lymphocytes that do not possess the phenotype surface markers of either T or B cells. Some may be identical to ‘Killer’ (k) cells, which have cytotoxic properties against target cells coated with antibody, and some may be ‘Natural Killer’ (NK) cells, which are thought to lyse certain tumour cells [1,16].

Citation: Weledji EP, Ngounou E. Immunity, Inflammation and Disease: What the Physician Should Know. Austin Immunol. 2023; 6(1): 1021.