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Cells and Organs of the Immune System

Anwarul Azim Akhand and Nazmul Ahsan

Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh

1.1 Introduction

Living animals grow in an environment that is heavily populated with both pathogenic and non-pathogenic micro-organisms. These micro-organisms contain a vast array of toxic or allergenic substances that may be life-threatening. Pathogenic microbes possess a variety of mechanisms by which they replicate, spread and threaten host functions. To counteract this array of threats, the immune system has evolved functional responses using specialised cells and molecules. The immune system is, therefore, a system of cells, organs and their soluble products that recognises, attacks and destroys any sort of threatening entity. By doing so, the immune system primarily protects us from various toxic substances and pathogens. At the same time, it essentially distinguishes dangerous substances from harmless ones. Infiltration with bacterial or viral molecules, for example, can be a dangerous attack on an organism, whereas inhalation of odorant or infiltration of food antigen into the bloodstream is harmless. The destruction of malignant cells is desirable but unnecessary attacks against host tissues are undesirable. Therefore, the cells of the immune system must be capable of distinguishing self from non-self and, furthermore, discriminating between non-self molecules which are harmful or innocuous (e.g. foods).

Two overlapping mechanisms are employed by the immune system to destroy pathogens: the innate immune response and the adaptive immune response. The first is relatively rapid but non-specific and therefore not always effective. The second is slower; it requires time to develop while the initial infection is going on. Although slower, this response is highly specific and effective at attacking a wide variety of microbial pathogens. The detailed mechanism of immune responses is discussed in Chapter 3.

The innate immune system has several first-line barriers that mostly act to limit entry and growth of microbial pathogens. These include physical barriers such as the skin, mucosal epithelia and bronchial cilia. Chemical and biochemical barriers include acidic pH of the stomach and sebaceous gland secretions containing fatty acids, lysozyme and beta-defensins. Once a pathogen overcomes these barriers and gains access to the body, cellular components must come forward to combat the invading organisms.

The immune response to a pathogen depends on sequential and integrated interactions among diverse innate and adaptive immune cells. Innate immune cells mount a first line of defence against pathogens, as antigen-presenting cells communicate the infection to lymphoid cells, which then co-ordinate the adaptive response and generate memory cells that help to prevent future infections. The cells of the innate and adaptive immune response normally circulate in the blood and lymph, and are also scattered throughout tissues and lymphoid organs. The primary lymphoid organs, including the bone marrow and thymus, regulate the development of immune cells from immature precursors. The secondary lymphoid organs - including the spleen, lymph nodes and specialised sites in the gut and other mucosal tissues - co-ordinate the antigen encounter with antigen-specific lymphocytes and their development into effector and memory cells. Blood vessels and lymphatic systems connect these organs, uniting them into a functional whole.

1.2 Hematopoietic Stem Cells: Origin of Immune Cells

Most immune system cells arise from hematopoietic stem cells (HSCs) in the fetal liver and postnatal bone marrow. HSCs are pluripotent cells, i.e. they have the potential to produce all blood cell types. They also have self-renewal capability. Remarkably, all functionally specialised, mature blood cells (erythrocytes, granulocytes, macrophages, dendritic cells and lymphocytes) arise from a single HSC type (Figure 1.1). The process by which HSCs differentiate into mature blood cells is called haematopoiesis. The differentiation of HSCs into various types of immune cells occurs under the influence of cytokines. Two primary lymphoid organs are responsible for the differentiation of stem cells into mature immune cells: the bone marrow, where HSCs reside and give rise to all cell types; and the thymus, where T cells complete their maturation. First, let us focus on the structural features and function of each cell type that arises from HSCs.

1.3 Cells of the Immune System

The immune system may seem like a less substantial entity than the heart or liver; however, immunity collectively consumes enormous resources, producing a large number of cells that it engages for successful function. After being produced from the bone marrow, the immune cells undergo significant secondary education before they are released to patrol the body. Many immune cell types have been identified and extensively studied. Among them, blood leucocytes provide either innate or specific adaptive immunity. They are derived from myeloid or lymphoid lineages. The myeloid lineage produces highly phagocytic cells, including polymorphonuclear neutrophils (PMN), monocytes and macrophages that provide a first line of defence against most pathogens (Table 1.1; see also Figure 1.1). The other myeloid cells include polymorphonuclear eosinophils, basophils and their tissue counterparts - mast cells. They are involved in defence against parasites and in allergic reactions. The lymphoid lineage produces cells that are mainly responsible for humoral immunity (B lymphocytes) and cell-mediated immunity (T lymphocytes).

Figure 1.1 Haematopoietic stem cells produce all blood cells by a process of haematopoiesis.

Table 1.1 Myeloid cells and their properties.

Cell Morphology Count/L Function Neutrophil PMN granulocyte 2 to 7.5 × 109 Phagocytosis and killing of microbes Eosinophil PMN granulocyte 0.04 to 0.44 × 109 Allergic reactions, defence against parasites Basophil PMN granulocyte 0 to 0.1 × 109 Allergic reactions Mast cell PMN granulocyte Tissue specific Allergic reactions Monocyte Monocytic 0.2 to 0.8 109 Phagocytosis and antigen presentation. Mature as macrophages in the tissue Macrophage Tissue specific Tissue specific Phagocytosis and antigen presentation Dendritic cell Monocytic Tissue specific Antigen presentation, initiation of adaptive responses

PMN, polymorphonuclear neutrophils.

1.4 Cells of the Myeloid Lineage: First Line of Defence

Myeloid cells are the front-line attacking cells during an immune response. Cells that arise from a common myeloid progenitor include erythroid cells such as red blood cells (RBCs) and myeloid cells such as white blood cells (granulocytes, monocytes, macrophages and some dendritic cells). Granulocytes are identified by characteristic staining patterns of 'granules' that are released in contact with pathogens. Granulocytes mainly include neutrophils, basophils and eosinophils.

1.4.1 Neutrophils

Neutrophils are the most abundant of the leucocytes, normally accounting for 50-70% of circulating leucocytes. They have a short life span. They circulate in the blood for 7-10 hours and then migrate to the tissue spaces, where they live only for a few days and do not multiply. During an active infection, the number of circulating neutrophils may increase two- to three-fold. Some neutrophils may remain attached to the endothelial lining of large veins and can be mobilised during inflammation. Neutrophils are about 10-20 µm in diameter and their nucleus is segmented into 3-5 connected lobes; hence they are called polymorphonuclear leucocytes. These cells are highly motile which allows them to move quickly in and out of the tissue during infection. They use their granules to ingest, kill and digest pathogenic micro-organisms. The primary granules include cationic defensins and myeloperoxidase. The secondary granules mostly include iron chelators, lactoferrin and various proteolytic enzymes such as lysozyme, collagenase and elastase. They do not stain with either acidic or basic dyes. The azurophilic granules are mostly lysosomes. Neutrophils dying at the site of infection contribute to the formation of the whitish exudate called pus.

1.4.2 Basophils

Basophils are a type of bone marrow-derived circulating leucocyte. They are also highly granular but with mononuclear appearance and are 12-15 µm in diameter. They account for less than 0.2% of leucocytes, and are therefore difficult to find in normal blood smears. They contain histamine, do not participate in phagocytosis and share many similarities with mast cells. In...