Immunodeficient Rodents A Guide to Their Immunobiology, Husbandry, and Use (1989) / Chapter Skim
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1 INTRODUCTION
1 INTRODUCTION
Pages 1-35
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Some of the mutations are allelic; others, although exhibiting similar pathologic processes, are not. The ability to establish these mutations in inbred strains and to develop congenic lines has greatly enhanced the usefulness of these models and fostered a better understanding of mutant gene effects.
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Many of these organisms have the capacity to replicate within the animal's body and cause disease; however, they are prevented from establishing an infection by a complex system of interacting innate and adaptive immune mechanisms. The innate defense system includes the integrity of the skin and mucous membranes; mucous secretions; cilia of epithelial cells on mucous membranes, which generate a mucous stream; nonspecific inflammatory processes; phagocytic cells; large granular lymphocytes, which function as natural killer cells; and biologically active molecules, such as histamine, complement, and other acute-phase reactants.
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These innate defense system components direct and magnify the neutralizing effects of antibody on a specifically targeted foreign substance. The recruitment of various non
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are glycoproteins with a basic four-chain structure composed of two large heavy chains, which are covalently linked by disulfide bonds, and two smaller light chains, which are attached to the heavy chains by disulfide bonds. The region where heavy chains are united is called the hinge region.
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In addition, each species has both kappa and lambda light chains, again based on common amino acid sequences. Because immunoglobulin molecules are secreted intact from a B lymphocyte, both heavy chains are identical, and likewise, both light chains are identical.
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regions and variable (V) regions in both the light and heavy chains.
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The generation of the Ti receptor uses complex genetic rearrangements of variable-region determinants, which allows for receptor diversity and specificity. The basic mechanism of joining V, D, and C regions is similar to that seen for immunoglobulin heavy chains.
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Afferent, Central, and Efferent Limbs of the Immune System The sequence of events that occur from the moment a foreign substance enters the body until it is destroyed or neutralized is highly coordinated and involves both nonspecific and specific immune defenses. To aid in the description of the events confronting the immune system, scientists have designated all events occurring before the activation of T and B lymphocytes as the afferent phase, all activities involving the specific interaction of antigen with lymphocytes as the central phase, and the activity of effecter mechanisms in neutralizing or destroying the foreign substance as the efferent phase.
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For those antigens that require T- and B-cell interactions to achieve antibody synthesis, T lymphocytes must recognize class II MHC antigens on the surface of antigen-presenting cells. This two-point recognition system, that is, foreign antigen and MHC determinants, allows T and B cells to come into close apposition.
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are lymphocytes or monocytes that bear the Fc receptor for antibody heavy chains. These cells become armed with specific antibodies and deliver a combined assault known as antibody-dependent cellular cytotoxicity on targeted cells.
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The integrity of primary tissues responsible for lymphocyte development (thymus and bone marrow) , the precise lymphoid cell population or subpopulation absent or perturbed in development, the nonspecific cellular defense involved in an abnormality, the molecular basis of the defect, and, finally, the precise genetic basis of the compromised immunologic function are all important in the final classification.
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Many infectious agents (e.g., Sendai virus, MHV, reovirus 3, LDV, LCMV, and MVM) are found as contaminants in transplantable tumors and tumor cell lines (Stanley, 1965; Collins and Parker, 1972; Biggar et al., 1976)
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is associated with a significant immunosuppressive action. For example, in mice, infection with Gross virus produces a persistent, progressive, and profound inhibition of antibody production and a depression of cell-mediated immunities, including skin allograft rejection (Dent, 19721.
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For these reasons investigators must maintain laboratory animal models free from infection by pathogens. GENERAL CONSIDERATIONS FOR MAINTAINING IMMUNODEFICIENT RODENTS An investigator desiring to work with immunodeficient rodents should first be familiar with standard husbandry practices in conventional, specific-pathogen-free (SPF)
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This document addresses the nonimmunologic deficits separately and provides guidelines for the proper care of these animals. It is an additional obligation of investigators who use these animals to monitor their well-being regularly; to minimize their suffering whenever possible; and, when necessary, to perform euthanasia in conformity with the recommendations of the American Veterinary Medical Association Panel on Euthanasia (19861.
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J Hedrich, Central Institute for Laboratory Animal Breeding, Hannover, Federal Republic of Germany.
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It defines the basic genetic characteristics of the animal and enables investigators in separate laboratories to compare their experimental results. Listing only the strain name of an animal in a research paper is not sufficient, because the genetics of different substrains of an inbred strain (e.g., the C3H strain of mice)
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J Hedrich, Central Institute for Laboratory Animal Breeding, Hannover, Federal Republic of Germany (1988)
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No sources are given for the immunodeficient rodents discussed in this report because of the rapidly changing nature of commercial and research animal colony holdings. To locate these models, contact the Animal Models and Genetic Stocks Information Program of the Institute of Laboratory Animal Resources, National Research Council, 2101 Constitution Avenue.
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Genetic Monitoring of Inbred Strains of Rats. A Manual on Colony Management, Basic Monitoring Techniques, and Genetic Variants of the Laboratory Rat.
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Key Terms
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