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). MALT is present 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 asphytohaemoglutinin (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 ].
Polymorphonuclear granulocytes (neutrophils) originate from bone marrow derived myeloid cells, and circulate in the bloodstream. Neutrophils live for 6-20 h and constitute approximately 60% of the total number of leucocytes. They bear surface receptors for IgA, IgG and complement components. Neutrophils play a primary role in non-specific immunity by engulfing and digesting microorganisms, and their absence usually proves fatal [17].. Mast cells are present in the skin and mucosal surfaces, and basophils circulate in the blood, where they constitute 0.5 to 2% of the circulating leucocytes. Although direct proof of common origin is lacking both mast cells and basophils are involved in type 1 immediate hypersensitivity reactions, when they release inflammatory mediators following allergen binding to IgE on their surface . They also bear receptors for complement components. Circulating basophils show an increase in allergic disease states and are seen in secretions of patients with allergic rhinitis. Eosinophil granulocytes originate from myeloid precursors in the bone marrow and circulate in the bloodstream, where they constitute 2-5% of the total number of leucocytes, although they may account for up to 20% in individuals with immediate sensitivity diseases or helminth infestation. They live for 6-20 h and bear receptors for IgG and complement components. Thus their primary activities are to engulf and digest immune-complexes important against helminth infection, and the release of enzymes that are able to inactivate biologically-active substances such as histamine in type I hypersensitivity reactions [18].