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biopharmaceuticals biochemistry and biotecnology - Walsh G.

Walsh G. biopharmaceuticals biochemistry and biotecnology - John Wiley & Sons, 2003. - 572 p.
ISBN 0-470-84327-6
Download (direct link): biochemistryandbiotechnology2003.pdf
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Leukocytes (white blood cells) encompass all blood cells that contain a nucleus, and these cells basically constitute the cells of the immune system. They thus function to protect the body by inactivating and destroying foreign agents. Certain leukocytes are also capable of recognizing and destroying altered body cells, such as cancer cells. Most are not confined exclusively to blood, but can circulate/exchange between blood, lymph and body tissues. This renders them more functionally effective by facilitating migration and congregation at a site of infection.
Leukocytes have been sub-classified into three families: mononuclear phagocytes, lymphocytes and granulocytes. These can be differentiated from each other on the basis of their interaction with a dye known as Romanowsky stain.
Mononuclear phagocytes consist of monocytes and macrophages and execute their defence function primarily by phagocytosis. Like all leukocytes, they are ultimately derived from bone marrow stem cells. Some such stem cells differentiate into monocytes, which enter the bloodstream from the bone marrow. From there, they migrate into most tissues in the body, where they settle and differentiate (mature) to become macrophages (sometimes called histocytes). Macrophages are found in all organs and connective tissue. They are given different names, depending upon in which organ they are located (hepatic macrophages are called Kupffer cells, CNS macrophages are called microglia, while lung macrophages are termed alveolar macrophages). All macrophages are effective scavenger cells, engulfing and destroying (by phagocytosis) any foreign substances they encounter. They also play an important role in other aspects of immunity by producing cytokines, and acting as antigen-presenting cells.
Lymphocytes are responsible for the specificity of the immune response. They are the only immune cells that recognize and respond to specific antigens, due to the presence on their surface of high-affinity receptors. In addition to blood, lymphocytes are present in high numbers in the spleen and thymus. They may be sub-categorized into antibody-producing B lymphocytes, T lymphocytes, which are involved in cell-mediated immunity, and null cells.
T lymphocytes may be sub-categorized on a functional basis into T helper, T cytoxic and T suppressor cells. T helper cells can produce various cytokines, which can stimulate and regulate the immune response. T cytotoxic cells can induce the lysis of cells exhibiting foreign antigen on their surfaces. As such, their major target cells are body cells infected by viruses or other intracellular pathogens (e.g. some protozoa). T suppressor cells function to dampen or suppress an activated immune response, thus functioning as an important ‘off5 switch.
Most T helper cells express a membrane protein termed CD4 on their surface. Most T cytotoxic and T suppressor cells produce a different cell surface protein, termed CD8. Monoclonal antibodies specifically recognizing CD4 or CD8 proteins can thus be used to differentiate between some T cell types.
Null cells are also known as ‘large granular lymphocytes’ but are best known as ‘natural killer’ (NK) cells. These represent a third lymphocyte sub-group. They are capable of directly lysing cancer cells and virally infected cells.
192 BIOPHARMACEUTICALS
Box 4.1. Leukocytes, their range and function (continued)
The third leukocyte cell type are termed granulocytes, due to the presence of large granules in their cytoplasm. Granulocytes, many of which can be activated by cytokines, play a direct role in immunity and also in inflammation. Granulocytes can be sub-divided into three cell types, of which neutrophils (also known as polymorphonuclear leukocytes; PMN leukocytes) are the most abundant. Attracted to the site of infection, they mediate acute inflammation and phagocytose opsonized antigen efficiently due to the presence of an IgG Fc receptor on their surface. Eosinophils display a cell surface IgE receptor and thus seems to specialize in destroying foreign substances that specifically elicit an IgE response (e.g. parasitic worms). These cells also play a direct role in allergic reactions. Basophils also express IgE receptors. Binding of antigen-IgE complex prompts these cells to secrete their granule contents, which mediate hypersensitivity reactions.
Table 4.2. Cytokines, as grouped on a structural basis
Cytokine family Members
‘b-Trefoil’ cytokines Fibroblast growth factors
Interleukin-1
Chemokines Interleukin-8
Macrophage inflammatory proteins
‘Cysteine knot’ cytokines Nerve growth factor
Transforming growth factors
Platelet-derived growth factor
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