Involved in the Immune Response

A large number of cells are involved in the immune response and all are derived fiom the multipotential stem cells of the bone marrow. The predominant cell is the lymphocyte but monocytes-macrophages, endothelial cells, eosinophils and mast cells are also involved with certain immune responses. The two types of immunity (humoral and cell-mediated) are dependent on two distinct populations of lymphocytes, the B cells and the T cells respectively. Both the humoral and the cell-mediated systems interact to achieve an effective immune response. 

Two different systems are involved in the immune response. The innate immune system is based on receptors that can distinguish between bacterial and viral surface structures or foreign proteins (known as antigens) and those that are endogenous. With the help of these receptors, phagocytes bind to the pathogens, absorb them by endocytosis, and break them down. The complement system (see p. 298) is also part of the innate system. 

The transcription activator NF B regulates a variety of genes involved in the immune response and the inflamatory process. NF B is required for the expression of genes for the light x-chain of immimoglobulins, interleukin 2 and 6, as well as for interferon b (see chapter 11). 

Thymus organ that forms cells involved in the immune response. 

As previously indicated, the primary cells involved in the immune response are lymphocytes which have a centrally located round nucleus, lack specific granules, and have a basophilic cytoplasm containing free ribosomes. The (thymus-dependent) T-lyniphocytes are involved in cell mediated reactions and also interact with B-Iymphocytes (see later) to regulate the production of antibody, The B cells differentiate into the antibody-producing plasma cells. There is growing evidence that neither T... 

The two classes of MHC proteins are displayed on different cell types. Class I MHC proteins are found on almost all nucleated cells, including killer T cells. Class II MHC proteins are found mainly on cells involved in the immune response, including antigen-presenting cells, B cells, and T helper cells, but not T killer cells. 

Mechanism of Action. Cyclosporine and tacrolimus (see below) are known as calcineurin inhibitors because they inhibit a specific protein (calcineurin) in lymphoid tissues. This inhibition ultimately suppresses the production of IL-2, a cytokine that plays a critical role in immune response by promoting the growth and proliferation of activated T lymphocytes and other immune cells, such as NK. cells (see Fig. 37—1).5,52 Thus, cyclosporine is one of the premier immunosuppressants because of its relative selectivity for T cells and its inhibition of a key mediator of the immune response (IL-2).41 This relatively specific inhibition is often advantageous when compared with other nonse-lective drugs such as azathioprine, cyclophosphamide, and glucocorticoids that inhibit virtually all the cells and chemical mediators involved in the immune response. 

Lymphocytes are one of the primary cell types involved in the immune response. There are two general types of lymphocytes, B and T. Both are derived from bone marrow lymphoid stem cells, but T cells go through an additional maturation process in the thymus. Although the morphology of T cells and B cells is similar, the functions of these two types are distinct. After antigen exposure, B cells develop into antibody-producing plasma cells, whereas T cells are divided into functional subtypes that possess distinct cell surface antigens. 

Figure 8-7. Development routes of the principal components involved in the immune response. Macrophages, which play an important accessory role in the immune response have been omitted.

Some cell-surface receptors are attached to the plasma membrane by lipids that penetrate only into the outer leaflet of the bilayer. Posttranslational modification of proteins with GPI-lipids allows proteins such as folate receptor-2 (FOLR2) to attach to the cell surface and promote RME of the vitamin 5-methyltetrahydrofolate. Folate receptors are upregulated in certain cancers, and folate derivatives have been linked to drugs and molecular probes to treat and image certain tumors. The related GPI-linked receptor FcyRIIIB (CD16, 26.2 KDa, Fig. 1) is involved in the immune response. This receptor binds the invariant Fc region of immunoglobulin-G to promote RME of this... 

Immunity in humans can be conceptualized in a number of different ways. If ju.sl the type and specificity of the immune response are considered, the ideas of initaie and acquired immunity arc used. If only the components that arc involved In the immune response are considered, the processes can be divided into himioral and cellular immunity. If the location of the immune response is considered, we find that the immune system consists of seraxal (in the serum) immunity and mucasal (on mucosal epithelium surfaces) immunity. 

Fig. 8.1 An overview of the cells involved in the immune response both innate and adaptive components. The cells arise from a pluripotent progenitor cell within the bone marrow, with their growth and differentiation controlled by numerous growth factors. The T lymphocytes differentiate in the thymus gland.

Flavonoids affect the immune system and the body s inflammatory cells. This function is partly accomplished through the effects on enzymes involved in the immune response and the generation of inflammatory cells. Balentine et al. (1999) recently reported that only the aglycon cyanidin, not the anthocyanin glycoside, showed inhibitory effects on enzymes involved in inflammatory activity. The anthocyanins can be metabolized into their glycoside-free constituents either before or after absorption in the gut and may thereby act as anti-inflammatory agents in the body. Middleton and Kandaswami (1994) stress the fact, however, that as most of these studies have been carried out as in vitro experiments, care should be taken not to draw too extensive conclusions for the in vivo actions of flavonoids. Fundamental biochemical research is needed before the mechanisms behind the diverse actions of flavonoids are fully understood. 

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