Basis of the Immune Response

There are four main types of hypersensitivity reactions type I, II, and III hypersensitivity reactions are associated with the production of antibodies while type IV is cell mediated. Immediate hypersensitivity (type I) is due to IgE elicited by the antigen that binds to Fee receptor of mast cells or eosinophils, leading to their activation. Asthma due to platinum salts might be due to specific IgEs that have been found in sensitized patients. In addition, it seems that this agent triggers IgE production in rats (Pepys 1983). However, to our knowledge, this model has not been extensively studied. Type IV or delayed type hypersensitivity (DTH) is probably due to THl cells and is probably frequently involved in metal-mediated adverse side reactions. 

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E. S. Golub, The Cellular Basis of the Immune Response, Sinauer Assocs., Sunderland, Mass., 1977. 

An important distinction must be made between the humoral response to a pure, capsular polysaccharide, and to the same polysaccharide when it is an integral part of the bacterium. Thus, the immunity received on recovery from infection by encapsulated bacteria, in terms of the polysaccharide antigen, differs from that generated by purposeful immunization with purified capsular-polysaccharide vaccines. Fortunately, with the exception of infants, the polysaccharide vaccines still stimulate protective-antibody levels in humans, despite these differences. In infants, due to the immature nature of their immune systems, these polysaccharide vaccines are of only marginal benefit.7 Some insights into the nature of these different responses in humans can be found in studies on the cellular basis of the immune response to polysaccharides. However, for the purposes of this Chapter, it would be inappropriate to provide a lengthy description of this incompletely understood mechanism in-depth reviews of this burgeoning field of research can be referred to.144-147,162-166... 

The cellular basis of the immune response consists essentially in a phenomenon of multiplication and differentiation of T and B lymphoc34 es stimulated by the antigen processed in macrophages. The selection of the specific clone of lymphocytes is made by the stereospecific combination of antigen determinants with pre-existing receptors on the lymphocyte surface. In B lymphocytes, these receptors are immunoglobulins the nature of the receptors in T lymphocytes is still controversial. 

Newer uses have appeared in the treatment of viral diseases including AIDS, alteration of the immune response, and cancer. The lithium salt of 7-linolenic acid (LiGLA) has a significant anticancer effect against certain cancers. The neurochemical basis for lithium action is difficult to define. Lithium carbonate induces a wide range of intra- and extracellular changes—most emphasis has been naturally on the similarities with Na/K/Ca/Mg ions. Lithium selectively interferes with the inositol lipid cycle, representing a unified hypothesis of action. The biochemistry, distribution, and cellular localization of lithium has been extensively documented. 

Table 9.3 The range of cells expressing the IL-2 cell surface receptor. IL-2-stimulated growth and differentiation of these cells forms the molecular basis by which many aspects of the immune response are activated. It thus acts in an autocrine and paracrine manner to mobilize...

Our knowledge of how the immune system functions in both normal and disease states has increased dramatically over the last several decades, and we now have drugs that can moderate the effects of the immune response in certain clinical situations. Immunosuppressants are a mainstay in preventing tissue rejection, and much of the current success of organ transplants is due to the judicious use of immunosuppressive drugs. These drugs are also beneficial in a number of diseases that have an autoimmune basis, and immunosuppressants can help alleviate symptoms or possibly even reverse the sequelae of certain diseases... 

We were unable to avoid some redundancy. For example, it seemed necessary to consider allotypy, idiotypy, and amino acid sequences in separate chapters. Yet each subject is intimately related to the genetic control of the immune response. Therefore, similar generalizations are sometimes drawn from the data presented in the three sections. Chapter 12 on theories of the genetic basis of structural variability attempts to draw these discussions together. 

The impact of these molecules in disease resistance remains unknown, but a better understanding of the molecular basis of bivalve immune response may allow these genes to be used as markers for disease resistance selection programmes. 

Alloimmunity is the immune response mounted by a host on the basis of differences in major histocompatibility antigens expressed on the surface of a donor cell from the same species as the host. 

Taken as a whole, these observations show that parasite lines differ in an immune-dependent manner in their infection/expulsion kinetics. Furthermore, there is heritable variation in survival and fecundity in previously exposed hosts and quantitative variation in the immune response that selected parasite lines elicit. Again, taken as a whole, these observations have the necessary corollary that variation in these traits exists not only in laboratory-maintained isolates but also in helminth species in nature. The phenotypes under consideration here (infection/expulsion kinetics, survival, fecundity) are multifactorial life-history traits. Understanding the basis of variation in the components and interplay of these complex, immune-responsive phenotypes must be of crucial relevance to understanding the immunology of infections of parasitic nematodes. This is of particular relevance in view of current attempts to develop immunological methods of nematode control. 

Other contributions to this book have taken a molecular view of parasitic nematodes, yet molecules make only a rather brief appearance here. This chapter has tried to show that parasitic nematodes are fascinatingly and tantalizingly diverse at a phenotypic level. It has focused particularly on diversity in phenotypes that are apparent in response to environmental conditions within or outside a host. The interaction of parasites with within-host factors is a major current research effort. However, helminth immunology is particularly notable for its inattention to diversity, especially when compared with the immunology of parasitic protozoa (Read and Viney, 1996). Observations of the interaction of host immunity with subsequent development in S. ratti show the potential power of such interactions. It is also clear that a principal mechanism of the action of host immune responses is against nematode fecundity (Stear et al., 1997). This is likely to be a molecularly complex interaction. Understanding this interaction, as well as variation in the interaction is interesting, but could also form the basis of control by transmission-reduction rather than eradication per se. 

Initial classification of some cytokines was also undertaken on the basis of the specific biological activity by which the cytokine was first discovered (e.g. TNF exhibited cytotoxic effects on some cancer cell lines CSFs promoted the growth in vitro of various leukocytes in clumps or colonies). This, too, proved an unsatisfactory classification mechanism, as it was subsequently shown that most cytokines display a range of biological activities (e.g. the major biological function of TNF is believed to be as a regulator of both the immune and inflammatory response). More recently, primary sequence analysis of cytokines coupled to determination of secondary and tertiary structure reveal that most cytokines can be grouped into one of six families (Table 8.2). 

Wallace. The influence of cigarette tobacco smoke products on the immune response. The cellular basis of immunosuppression by a water-soluble condensate of tobacco smoke. Immunology 1980 40(4) 621-627. 

Immunoglobulin. Immunoprotein glycoprotein of animal origin with known antibody activity, or protein related by chemical structure, which may or may not have antibody activity. Divided into five classes IgM, IgG, IgA, IgD, and IgE on the basis of structure and biological activity. Immunostimulant. Stimulating various functions or activities of the immune system. Immunosuppressant. An agent capable of suppressing immune responses. 

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