Plasma cells antibody production

Figure 1.7. Lymphocyte activation. When naive lymphocytes first encounter the antigen that is recognised by their receptor, they are stimulated to differentiate and proliferate. This clonal expansion is aided by the production of cytokines. Two cell types develop from this process the effector cells (i.e. either antibody-secreting plasma cells or cytotoxic T cells) and memory cells. Both cell types possess virtually the same receptor that was expressed on the naive lymphocyte.

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

There are two main types of immune response cell mediated and humoral. Cell-mediated immunity involves specifically sensitized thymus-dependent lymphocytes. Humoral immunity involves the production of antibodies (immunoglobulins) from lymphocytes or plasma cells. The mechanisms will be discussed in more detail below. 

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... 

After recognizing antigens through membrane-bound antibodies, there is B cell proliferation and differentiation for about 4-5 days. This results in the production of plasma and memory cells. One of the five classes of antibodies are produced and secreted by plasma cells that do not possess membrane-bound antibodies. Plasma cells survive for about 1-2 weeks. 

The difference between a normal immune response and a type I hypersensitive response is that in the latter, plasma cells secrete IgE. This class of antibody binds to Ec receptors on the surface of tissue mast cells and blood basophUs. Mast cells and basophUs coated by IgE are sensitised . Later exposure to the same allergen cross-links the bound IgE on sensitised cells, resulting in degranulation and the secretion of pharmacologically active mediators such as histamine, leukotrienes and prostaglandins. The principal effects of these products are vasodilation and smooth-muscle contraction (Table 15.6). 

It has been shown that T lymphocytes have AChE located on the plasma membrane, while B cells are esterase negative (Szelenyi et al, 1982). Thus, AChE inhibition by toxic agents in sublethal doses may play an important role in immunodeficiency following exposure to nerve gases. Zabrodskii et al (2003) showed inhibition of AChE in T cells and the decrease in the number of esterase-positive T lymphocytes (and, to a certain extent, in monocytes and macrophages) directly correlated with suppression of T cell-dependent antibody production and to the degree of DTH reduction, on exposure to dimethyl dichlorovinyl phosphate, sarin, VX, lewisite, tetraethyl lead, and dichloroethane. This presumably involves the loss of some functions by T... 

The present discussion is mainly concerned with the humoral response. Although many cells participate in this response, the site of antibody production is in B lymphocytes which, in their mature form, are called plasma cells. Each plasma cell produces antibodies with a given specificity, and there are many identical copies, or clones, of this cell type, all making the same monoclonal antibody. Other lines of plasma cells produce antibodies that recognise the same antigen, but have different... 

Figure 33.1. Immunoglobulin Production. An electron micrograph of a plasma cell shows the highly developed rough endoplasmic reticulum necessary for antibody secretion. [Courtesy of Lynne Mercer.]...

An animal immunized with an antigen (Ag) increases its population of antibody (Ab)- producing lymphocytes. These cells are short lived and can exist in cell cultures only for a few days. Malignant plasma cells are separately cultured. These cells are essentially immortal, and can be cultured for years, but they are poor producers of Abs. Some malignant plasma cells are deficient in the enzyme hypox-anthine phosphoribosyltransferase (HPRT), and will die unless HPRT is supplied to the culture medium. These are the malignant cells that are used for the production of hybridomas. 

The variable amino acid sequence at the amino terminal end of each chain determines the antigenic specificity of the particular antibody. Each unique amino acid sequence is a product of a single plasma cell line or clone. The normal host response to an immunogen results in the stimulation of one or two major classes of lymphocytes that are able to divide and produce plasma ceUs capable of secreting antibodies. Each plasma cell line produces antibodies with a single specificity. A complex antigen is capable of eliciting a multiplicity of antibodies with different specificities that are derived... 

After antigenic presentation to CD4 and CDS cells, there is a set of effects on other lymphocytes in which the suppressive ability on the proliferation of B lymphocytes is enhanced through CDS cells. This prevents them from becoming plasma cells and ensures that they produce antibodies. In the case of CD4 (as classical helpers ), they stimulate B lymphocytes and consequently their conversion into plasma ceils and the production of antibodies. 

CD4 lymphocytes have two subtypes T helper (Th)l and Th2 (Figure 22-4). Th2 is the common CD4 helper that helps B lymphocytes to be transformed into plasma cells, leading to the production of antibodies. Thl lymphocytes are implied in a cytotoxic and cytolytical process similar to that developed by CD8 cells, which are not only classical sup-... 

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