Immune system leukocytes

In designing drugs to target immune-mediated messengers, it is important to appreciate the anatomy and biochemistry of the immune system. The anatomy of the immune system is not nearly as well delineated as that for the other messenger systems, such as the nervous system. The foot soldiers of the immune system are the leukocytes (white blood cells), which do the majority of the work within the immune system. Leukocytes may be subcategorized as follows ... 

The CB2 receptor has a more limited distribution, being localized predominantly in the immune system. Among the human leukocytes, B lymphocytes express the highest levels of CB2, followed respectively by natural killer cells, monocytes, polymorphonuclear neutrophils, T8 lymphocytes, and T4 lymphocytes. It is also found in the lymph nodes, spleen, tonsils, and thymus (Cabral, 1999). 

The circulatory system carries out many important functions that contribute to homeostasis. It obtains oxygen from the lungs nutrients from the gastrointestinal tract and hormones from the endocrine glands and it delivers these substances to the tissues that need them. Furthermore, it removes metabolic waste products, such as carbon dioxide, lactic acid, and urea, from the tissues. Finally, it contributes to the actions of the immune system by transporting antibodies and leukocytes to areas of infection. Overall, the circulatory system plays a vital role in maintenance of optimal conditions for cell and tissue function. 

There are normally 4000 to 11,000 leukocytes (white blood cells) per microliter of human blood. However, leukocytes act primarily within the tissues those found in the blood are actually in transit. Leukocytes are also found in lymphoid tissues such as the thymus, spleen, and lymph nodes. These cells are referred to as "white" blood cells because they lack hemoglobin and are essentially colorless. Leukocytes are an important component of the immune system. General inflammatory and immune functions of these cells include ... 

HA receptors are classified into 4 subtypes Hi, H2, H3, and H4 (Hill et al, 1997). All four HA receptor types are metabotropic receptors and belong to the superfamily of G-protein coupled receptors. Ionotropic HA receptors are found in invertebrates (Hardie, 1989 Gisselmann et al., 2002) but are absent from vertebrates (Haas Panula, 2003). Of the four HA receptors, only the Hi, H2, and H3 receptors are found in brain. The recently discovered H4 receptor is predominantly present on leukocytes and may have a critical role in the immune system (Nguyen et al., 2001 Bakker, 2004 Haas 8i Panula, 2003). 

Inflammation is the normal host response to infection or injury that mediates immune elimination of pathogens and tissue repair. Inflammatory processes include increased production of cytokines, chemokines, nitric oxide, and eicosanoids by the innate immune system in conjunction with altered leukocyte homing, all of which greatly impact acquired immunity. Aberrant inflammatory responses evoke both acute injury such... 

CSF levels in normal human serum are usually low or undetectable. During infections, the immune system responds by activation of leukocytes, and often this is accompanied by an increase in numbers of specific leukocytes in the circulation in order to combat the infective agent. Thus, it is not surprising that many pathogens activate CSF production, which then results in increases in numbers of progenitor cells in the bone marrow and spleen, and subsequent increases in numbers of mature leukocytes in the circulation. 

The various organs of the immune system such as spleen, lymph nodes, thymus and bone marrow containing the cells involved in the various immune responses offer the possibility to harvest these cells and perform in vitro assays for evaluation of effects on the immune system. When part of an in vivo animal study this may indicate a direct toxic effect of pharmaceuticals, that is, immunosuppression (Table 18.2). So, it is feasible to obtain cell suspensions for further evaluation such as determination of cellular subsets of T and B leukocytes by fluorescent activated cell sorter analysis (FACS analysis), and determination of natural killer (NK) cell activity of the spleen cell population. An advantage of this approach is that it may lead to identification of a biomarker to be used in clinical studies. In addition, in vitro stimulation of spleen cells with mitogens activating specific subsets may indicate potential effects on the functionality of splenic cell populations. Concanavalin A (Con A) and phytohemagglutinin (PHA) activate Tcells, while lipopolysaccharide (LPS) activates primarily B cell populations. Blood is collected for total white blood cell (WBC) determination and blood cell differential count. In addition, serum can be obtained for determination of serum immunoglobulins. 

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