21.2Immune cells and structure


Immune cells are produced in the bone marrow

With regard to the cell cycle, tissues in higher animals can be divided into three types. The first type is tissue in which cells do not proliferate once the animal has reached maturity (e.g., nerve cells). In the second type, the cells are normally in the G0 phase of the cell cycle and are resting but can proliferate if required (e.g., hepatocytes). The third type of tissue is that in which cells continue to replicate constantly (e.g., epithelial cells). Cells involved in immune responses belong to the third group. They are produced in the bone marrow throughout an individual’s life and are distributed within the body as they differentiate (Figure 21-1). Bone marrow cells that can differentiate into all types of blood and immune cells are called hematopoietic stem cells. These cells enter the circulation after differentiating into erythrocytes, platelets, leukocytes and other cells (Table 21-1).

Leukocytes include neutrophils (whose main function is to ingest bacteria), eosinophils, and basophils. Eosinophils and basophils are related to the elimination of parasites. Together with macrophages, which are created through the differentiation of monocytes in the blood, all of these cells are involved in innate immunity and inflammation. However, they also play the role of effectors in acquired immune response (described below). Natural killer cells, which are a type of lymphocyte lacking T cell receptors and immunoglobulins, also act as effectors in acquired immune response.

Figure 21-1 Immune system cells differentiated from hematopoietic stem cells of the bone marrow and their distribution

Immune cells are characterized by their lineage, differentiation phase, and localization. They can be distinguished by morphology and the CD marker molecules expressed on the cell surface. The bone marrow and thymus are called primary lymphoid organs, in which immunoglobulin (B cell receptor molecules) and T cell receptor molecules are genetically recombined. Secondary lymphoid organs are the sites of immune response, in which lymphocytes (T and B cells) and antigen presenting cells interact. The differentiation and activation of these cells are regulated by cytokines, whereas their migration is regulated by chemokines.

Table 21-1 Major immune cells

Dendritic cells sense and capture foreign microorganisms, allergens, and denatured self-components; they subsequently process these proteins and present them to T cells. Dendritic cells play a critical role in initiating the acquired immune response, which is described below. Dendritic cells are a diverse group of cells derived from the bone marrow and are formed via multiple pathways.

Among lymphocytes, the T and B cells are mainly responsible for acquired immunity. These lymphocytes have T cell receptors and immunoglobulin respectively on their cell surfaces, which specifically bind to specific antigens. T cell receptor and immunoglobulin genes are recombined during proliferation and differentiation of these cells that take place in the thymus and bone marrow respectively. Through genetic recombination, these receptors can achieve almost infinitely diverse variations in the structure of the site that binds to antigens (see Selection 4 of Chapter 21). This mechanism for recombining specific genes is a feature unique to the vertebrate immune system and cannot be seen in other cells. Furthermore, only one type of recombined receptor molecule exists in each lymphocyte clone. Consequently, when lymphocyte clones respond to antigens and proliferate, the number of lymphocyte subpopulations with T cell receptors or immunoglobulins that can bind to a specific antigen increases. This is the essence of the acquired immune responses.

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Immune cell lineage and differentiation phase

As shown in Figure 21-2, cells of the immune system not only circulate in the blood and lymphatic vessels as leukocytes but are also distributed across various tissues of the body. These cells, in their entire life, monitor foreign invasion and pathological changes in cells in the body while changing their positions and differentiating to change the state of genetic expression. The lineage of numerous immune system cells and their differentiation phase have conventionally been classified and defined according to morphologic and staining characteristics. However, modern molecular genetic methods allow them to be clearly distinguished according to clusters of differentiation (CDs). CDs are cell surface marker molecules that can be identified and defined using monoclonal antibodies (see Appendix). While not as detailed and complete as the lineage mapping of all the cells in nematodes, the lineage and differentiation phases of immune system cells of higher animals have been well defined by combining over 300 CDs. The CDs are closely linked to the functional characteristics of various immune cells, and therefore the entire picture of the immune system in which diverse types of cells migrate from location to location while changing their characteristics is gradually being revealed.

Figure 21-2 Distribution of immune cells, changes in localization due to invasion by antigens

When antigens invade through damaged skin, dendritic cells in the skin ingest the antigens and move to the lymph nodes while processing them. There, the dendritic cells present fractions of the antigens that have been broken down into peptides. T cells circulating through the body adhere to high endothelium in the arteriola inside the lymph node, through which they enter the lymph nodes, then recognize the antigens and become activated.

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Primary and secondary lymphoid organs: site of immune cell growth

The lymphoid organs are sites at which immune cells exist in large numbers and where they proliferate, differentiate, and become activated. Cells destined to become T or B cells proliferate and undergo gene recombination of T cell receptor and immunoglobulin in the thymus and bone marrow, respectively, which are called primary lymphoid organs. Lymphocyte clones are cells responsible for acquired immunity and thus express only one type of receptor gene out of the diverse variations created through genetic recombination. Among the almost infinite variety of binding structures resulting from recombination, naturally, some receptors have recognition specificity for structures included in “self” components. Here, the primary lymphoid organs play an important role in the elimination of clones with such receptors to establish antigen-specific "immune tolerance."

Antigen-specific immune responses can be referred to as the proliferation and differentiation of cell clones that express receptor molecules with specificity for a certain antigen. It is in the lymph nodes, spleen and mucosa-associated lymphoid tissues (MALT), where T cells and antigen presenting cells such as dendritic cells and macrophages meet and initiate antigen-specific acquired immune responses, causing T cells to proliferate. Moreover, B cells also become activated at these sites to proliferate and differentiate into cells secreting immunoglobulin. These sites are called secondary lymphoid organs.

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