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- Index A Adaptive immune system/mechanisms, 2-10, 224 Adenosine deaminase, 85, 217; see also Severe combined immunodeficiency p-Adrenergic substances, 10 Allergic contact dermatitis, 81, 220 Alopecia, 57, 116; see also Mouse mutants nu; Rat mutants, rnu Amyloidosis, 116, 119, 122, 218 Antigens Anemia autoimmune hemolytic, 88, 97, 105- 106, 112, 220 defined, 218 macrocytic, 82-83 in osteopetrotic mutations, 51, 68 Antibiotics, and immunosuppression, 12 Antibodies anti-class II MHC, 132 anti-DNP, 135, 218 antihistone, 115 antinuclear, 50, 54, 61, 70, 88, 94, 99, 109, 114, 115, 122, 218 B cell production of, 3 deficiency in LPS-induced adjuvant response to, 63 enhanced production of, 142 function of, 3-4, 10 233 genetic mechanisms in diversification of, 6-7 T-cell-dependent responses, 140-141, 142 T-cell independent responses, 140- 141 thymocyte-binding, 88 viral inhibition of, 13 see also Autoantibodies; Immunoglobulins Antibody-dependent cytotoxic cells, 10, 217 Brucella, 50 defective responses to, 115, 116, 135, 136 designations, 2 IaW39, 86 I-E surface, 101 monoclonal antibodies reacting to, 213-215 resistance to tolerance induction by, 119 retroviral gp70, 108, 112 T-cell dependent, 116, 135- 137 T-cell independent, 116, 230 thymus-dependent, 85, 115, 230 thymus-independent, 85, 230 thyroid-stimulating hormone receptor (TSH), 14 see also Major histocompatibility complex antigens

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234 INDEX Anti-lymphocyte serum, 145, 217-218 Anti-theta serum, 145 Arteritis, 60, 99, 114, 121, 228 Arthritis, 14, 60 Ataxia telangiectasia, 84-85, 218 Autoantibodies against islet antigens, 101 anti-DNA, 50, 88, 91, 99, 105, 106, 108, 112-114 anti-double-stranded DNA, 54, 61, 66, 90, 91, 105, 108-109, 218 anti-erythrocyte, 105-106, 108 anti-gp70, 105, 107, 108, 110, 121 anti-insulin, 45, 104 anti-islet cell cytoplasmic antigens, 45 anti-pancreatic beta cells, 44-45 anti-p73, 104 anti-ribonucle:~c protein (RNP), 99 anti-RNA, 110 anti-single-stranded DNA, 61, 90, 91, 105, 106, 108, 121, 218 anti-Smith, 61, 99, 218 anti-thymocyte, 66,, 105 characteristic of aptoimmune disease, 14 cross-reactive idiotype families, 113 defined, 218 genes controlling, 108 natural cytotoxic antibodies (NCA), 106 reduced levels of, 91 thymus-binding, 54, 227 Autoimmunity/autoimmuine disease acceleration of, 87-89, 91, 93-94, 97, 112 autoantibodies characteristic of, 14 autoimmune polyendocrine disease, 14 B cell depletion and, 94 correction of, 107-108 defined, 2, 218 early-onset lymphoid hyperplasia with, 52 environmental factors in, 13-14 estrogen therapy and, 99 experimental autoimmune encephalomyelitis B cells (EAE), 95, 117-118, 120, 221 genes controlling susceptibility to, 105, 161 hemolytic anemia, 105 induced by MHV, 162 Ly-1+ B cell population and, 66 modification of natural history, 86-87 orchiectomy and, 88 progressive auto~mmune lymphoproliferative disease, 94 spontaneous, 13-14, 70, 101, 105 systemic lupus erythematosus, 54, 99, 105, 108-111, 114-115, 121, 122, 135 against thymic hormones, 45 without lymphoid hyperplasia, 99 Y-linked, 38, 87-89, 91, 93-94, 97 B B cell defects absence of mature cells, 92-94 atrophy, 101 and autoimmunity, 111, 113 blocked complement receptors on, 141 decreased numbers of cells, 47 diminished response to type I antigens, 86 functional lesions, 85-86 hyperactivity, 107, 111, 118- 119 in Ia expression, 63 in immunoglobulin expression, 63, 86, 107 inability to proliferate in presence of LPS, 63 increased function in mutants, 45, 126 ionizing radiation and, 145 Ly- 1 + population, 66, 86, 107 Lyb-3 expression, 86 in Lyb-5 subpopulation, 86, 92, 107 maturation factors, 98 polyclonal activation, 66 production of pathogenic IgG anti-DNA, 109 proliferative response impairment, 63, 66, 78 resistance to induction of immunologic tolerance, 107 in response to T-cell replacing factors, 98 sIg+ population, 86 thymic proliferation, 119 activation of, 9, 163 differentiation of, 3, 4, 6-7, 9, 116 function of, 3, 4, 8, 9, 218 immunoglobin secretion, 3, 5, 7 interaction with T cells, 3, 7, 9, 92, 98, 109, 112, 116, 119 maturation of, 91 proliferation of, 3, 4, 6-7, 9 see also Antibodies Babesia rodhaini, 143

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INDEX 235 Bacille Calmette-Guerin (BCG), 127 Bacillus enteritidis, resistance and susceptibility to, 94-96 Bacillus piliformis, 143 cells destruction of, 102, 133 necrosis of, 44 unrestricted hyperplasia of, 44, 72 Blastomyces dermatitidis, 163 Bone marrow, model of functional relationships with spleen and thymus, 93 Bone marrow defects decreased cells, 76 depression of granulocyte macrophage precursors, 141 hyperplasia, 105 increased myelopoiesis, 66 lack of marrow cavities, 129 in long bones, 52, 74 lymphocyte deficiencies, 77 plasma cell deficiencies, 77 preleukemic cells, 71 reduced erythropoiesis, 66 Bone marrow transplantation, correction of defects with, 42, 52, 69, 78, 83, 85, 107-108, 111, 124, 125 Bordetella pertussis, induction of histamine sensitivity by, 118, 120 Bronchopneumonia, 60 Butylatedhydroxyanisole, 141- 142 C Cadmium, immunosuppressive effects of, 11, 141 Calcitonin, 10, 51-52, 68, 74, 76, 219 Candida albicans, 137 Cell-mediated immunity, depressed, 45, 47, 49, 58, 66, 72, 110, 111, 141, 144 Cell surface antigens, monoclonal antibodies reacting to, 2, 213-215 Chediak-Higashi syndrome, 15, 41, 218 Chemotaxis decreased, in mutants, 4, 41-42 defined, 219 drug depression of, 12 in peritoneal macrophages, 68 Chromosome maps/gene markers humans, 6 information sources on linkages, 16 mouse, 6, 16-31 rat, 32-33 restriction fragment length polymorphism map, 86 Coccidioides immitis, 163 Complement system activation of, 3, 4, 6, 9-10, 55, 90 C1, 90 C2, 90, 134-135, 136 C3, 50, 115, 135-136, 137, 219 C4, 89-90, 129-130, 135, 136-138 C5, 54, 137 C6, 139 characteristics and functions of, 4, 9, 220 deficiencies, 129-130, 134-138, 139, 141 pathways (cascades), 4 regulator of complement activation (RCA), 90 role of classical pathway during infection, 137-138 S-region-linked genes controlling murine C4, 89-90 Complementarity-determining regions (CDRs), 109-110 ConA, impaired response to, 47, 84, 91, 127, 141, 145, 220 Congenic mouse strains A.SW, 117 BXSB-xid, 94 B10.D2/oSnJ, 55 C.B-Igh-Ib (CB17), 77-80 C57BL/KsJ.B6-H-2b, 73 NOD.NON-H-2, 100, 101 NZB.CB/N-xid, 106-107 SJL/J-lpr, 117 Congenic strains, defined, 16, 220 Conjunctivitis, 128 Corynebacterium parvam, 119, 127- 128 Coxsackievirus B4, 14 Cryptococcus neoformans 137 Cytolysis, 4 Cytomegalovirus, 143 D Demyelinating disease, susceptibility to, 117, 120, 162, 163 Dendritic cells follicular, antigen retention by, 126 function of, 3, 8, 221 Thy- 1 + epidermal cells, lack of, 77 see also Langerhans' cells

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236 INDEX Dextran, failure to respond to, 85 Diabetes mellitus characteristics of, 221 and congenital malformations, 134 environmental modifiers of, 101- 102 insulin-dependent, 100-101, 130-134 modifiers of severity, 44, 102 mouse models, 17, 37, 43-45, 100- 103 non-insulin-dependent, 44, 45 non-obese, 100-104, 132 orchiectomy and, 101 ovariectomy and, 101 prevention of, 102, 103, 132 rat models, 130- 134 resistance to, 44, 100, 131 spontaneous autoimmune, 100- 104 transfer of, 102 viruses associated with, 13- 14 Diabetogenic encephalomyocarditis virus, 73 Diet autoclaved, 128, 144 contamination through, 11, 103, 144, 152 for diabetic mice, 103 and immunosuppression, 11, 103, 144 magnesium-deficient, 144 restriction, 45, 73 soft, 69, 75, 76, 124, 125, 129 water, 152-153 Diethylstilbestrol, 140-141, 221 1,25-Dihydroxyvitamin D, 10, 68, 74, 124, 125 2,4-Dinitro-1-fluorobenzene (DNFB), contact sensitivity to, 81, 221 Dinitrophenol, increased PFC response to, 115 E Ectromelia virus, 143, 147, 161, 162 Encephalomyocarditis virus, 14, 163 Endogenous ecotropic virus, 121 Endoparasites, 10 p-Endorphin, 10 Endotoxin, see Lipopolysaccharide Eperythrozoon coccocides, 12 Escherichia colt, susceptibility to, 63 Estrogen, 10, 99 Experimental allergic encephalomyelitis (EAE), 95, 117-118, 120, 162, 221 F Facteur thymique serique, 50, 122, 221 Factor H expression, 90 Feline leukemia virus (FeLV), 13 Flaviviruses, 161-162, 163 G Gallic acid, 141-142, 221 Gamma-globulin, tolerance to, 80 Generalized arterial disease, 60 Generalized lymphoproliferative disease, 37, 52-54, 90 Giardia muris, 164 Glomerulonephritis, 60, 66, 88, 99, 107, 109, 112-114, 121, 122, 222 Glucagon, 14 Glucan, 146 Glucocorticoid increasing factor, 142-143, 222 Glucocorticoids, 10, 142-143, 222 Glucose intolerance, 101, 104 Glycosuria, 101 Glycosylation pathway, deficiency in, 86 Graft-versus-host reaction defined, 222 impaired, 46, 49, 58, 110, 119, 127, 142, 143 Gram-negative bacteria, 62 Granulocyte-macrophage colony-stimulating factor, 64, 222 Gross virus, 13 Growth hormone, 10, 14, 46 Growth retardation, 46, 49 Guinea pig mutants, see Table 2-1, p. 39 Guinea pigs, monoclonal antibodies reacting to cell surface antigens in, 213-215 H Halothane, 12 Hamster mutants, 1, 14; see also Table 2-1, p. 39 Hamsters immunoglobulin subclasses, 5 monoclonal antibodies reacting to cell surface antigens in, 213-215 Haptenated-Ficoll, failure to respond to, 85 Hemobartonella mur~s, 12 Henoch-Schonlein purpura, 135, 222 Heparin, 10

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INDEX 237 Hereford cows, partially albino, 41 Herpes simplex virus (HSV), 63, 143, 147, 161, 163 Histamine, 10, 118, 120, 223 Hodgkin's disease, 117 Hormones and host defense function, 10 and murine lupus erythromatosus, 111 Human chromosomes, 6 Human severe combined immune deficiency, model for, 77-79 Human T cell lymphotrophic virus type I (HTLV-I), 13 Humoral immunity, deficiencies in, 66, 144 Husbandry practices bedding, 153 caging or housing system, 112, 120, 148, 149, 151 cesarean derivation, 128 conventional environment, 14 defined-flora, 14, 71, 219, 221 disease surveillance, 154 environmental conditions, 14, 59, 151-153 filter hoods, 128, 149 general considerations, 14- 15, 69, 148-149, 151 germ-free isolation, 14, 67, 71, 75, 102, 127, 128, 133, 150-151, 222 HEPA-filtered laminar-air-flow systems, 149-150, 151, 223 and immunosuppression, 12, 50, 55 infection control in commercial stock, 153-154 insulin treatment for diabetic rodents, 203, 131 laminar flow, 133 pathogen-free environment, 1, 14, 43, 51, 71, 76, 79, 96, 108, 112, 121, 125, 127-129, 133, 139, 149, 219, 227, 229 prevention of fighting among rodents, 120, 154 retirement and replacement of breeders, 62 single-user, SPF, barrier-protected room, 79, 128 strict isolation, 14 temperature conditions, 59, 151 - 152 transfer of animals between facilities, 153-154 see also Diet Hybrid mouse strains (see also Table 2-1, p. 38) CBA/Ca x BXSB/Mp Fl, 94 CBA/N x BXSB/Mp Fl, 94 C3HeB/FeJ x C57BL/6J Fl, 159 C3HeB/FeLe x C57BL/6J Fit, 84 C57BL/6J x C3H/H Fit, 34 C57BL/6J x C3H/HeJ Fl, 34 C57BL/6J x C3H/HeSnJ Fl, 59, 160 C57BL/6J x C3HeB/FeJLe-a/a Fat (B6C3Fe-a/a Fl), 47, 48, 74, 75, 159, 160 C57BL/6J x SB/Le, 93 nomenclature, 34 NZB x NZW Fit (BWF~), 86-87, 99, 105, 121, 122 PN/Sw x NZB/Sw Fl or NZB/Sw x PN/Sw Fit, 114 SJL/J x BALB/c Fat, 120 WB/ReJ x C57BL/6J (WBB6F), 82 Hydrocephalus, 76 Hypercholesterolemia, 101 Hypergammaglobulinemia, 135, 223 Hyperglycemia, 43, 72, 101, 131- 132, 134 Hyperimmunoglobulinemia, 54, 88, 94 Hyperinsulinemia, 43, 44, 72 Hyperphagia, 43, 72 . . . . iypersensltlvlty reactions contact, 81 delayed-type, 12, 84, 119, 141, 142, 161, 221 enhanced responsiveness, 81 impaired, 119 vasoactivity amine, 118 Hypocalcemia, 68, 129 Hypophosphatemia, 68, 74, 129 Hypophysis, 49, 218 Hypothermia, 59, 63 I Immune complex circulating, increases in, 121 defined, 224 deposition in kidneys, 44, 66, 73 glomerulonephritis, 60, 88, 97, 109 reduced levels of, 91 retroviral gp70, 61, 99 serum gp70, 91, 105, 121 vascular disease, 88

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238 INDEX Immune system function, 2- 11 compromises in, see Immunodeficiencies/ 1mmunosuppress~on environmental factors affecting, 11- 14; see also Immunodeficiencies/ . . 1mmunosuppresslon 1 ~ hormones and, 10 immunodeficiency and, 10- 11 and infectious agents, 12-14 and lymphomagenesis, 57 and noninfectious agents, 11- 12 in nursing mice, 50 see also Adaptive immune system/ mechanisms Immunodeficiencies/immunosuppression and activation of latent infections, 143-144 by alkylating agents, 142 biological inducers, 145- 146 chemically induced, 140-143 classification of disorders, 11 defined, 2, 10, 224 drug-induced, 12, 13; see also Antibiotics; and specific drugs environmental causes, 10- 11 genetic causes, 10-11; see also Guinea pig mutants; Hamster mutants; Mouse mutants; Mutations; Rat mutants by glucocorticoids, 142- 143 by heavy metals, 11, 141 by infectious agents, 12- 14, 143- 144; see also specific agents by ionizing radiation, 144-145 and lymphoid malignancies, model for, 79 by noninfectious agents, 11- 12, 140-143, 144-147 nutrition and, 144 by phenols, 141-142 stress and, 11- 12, 50, 146 by thymectomy, 146- 147 by ultraviolet radiation, 145 X-linked, 85-87, 90-94 Immunoglobulins absence of, 84-85 B cell production of, 3, 5, 7 decreased levels of, 47, 70-71, 77, 85-86, 90, 94, 117, 138, 141 defect in expression of, 63, 86 defect in isotype switching, 136 function of, 5-6, 224 IgA, 50, 61, 70, 84-85, 88, 115, 126 IgD, 86, 126 IgE, 117 IgG, 5, 10, 47, 50, 59, 61, 63, 66, 70, 80, 88, 90, 91, 94, 106, 111, 113, 115, 118, 126, 134, 135, 136, 138, 141, 145, 146 IgM, 47, 49, 61, 66, 70, 86, 90, 91, 94, 105-107, 110-111, 113, 115, 135, 136, 145 increased levels of, 58, 61, 66, 91, 94, 105, 107, 110-111; see also Hyperimmunoglobulinemia kidney deposits of, 50, 66, 94, 115 Al, 118 and reticulum cell sarcomas, 118 rheumatoid factors, 61 species differences in, 5 structure of, 4-6 suppression of, 12 Immunologic specificity, see Adaptive immune system/mechanisms Inbred mouse strains (see also Table 2-1, p. 38) 129/J, 43, 44 A/HeJ, 62 A/J, 39, 119 AKR, 59, 61, 64, 69, 71, 98, 115-116 BALB/c, 39, 47, 56, 58, 59, 69, 77, 80, 109, 162, 163 BRVR, 94 BRVS, 95 BXD recombinant, 96 BXSB, 87-88, 91, 93, 96-98 CBA/MN, 85, 86 CBA/H-T6, 68 CTS, 104 C3H,98,100,116, 163 C3HeB/FeJLe, 64, 65 C3H/HeJ, 17, 34, 39, 40, 42-43, 49, 52-54, 59, 61-64, 86, 88, 90, 157-159 C3H/HeN, 17, 49, 64, 86 C57BL, 82 C57BL/Ka, 77 C57BL/Ks, 17, 43-45, 72-73, 157 C57BL/6, 17, 34, 39, 40-45, 49, 52, 59, 61, 63-65, 66, 67, 68, 72-73, 75, 80-84, 87, 88, 90-91, 96, 98, 119, 157-159, 162 C57BL/ 10, 109 C57BL/lOJ, 100 C57BL/lOScCr, 62

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INDEX C57BL/ 1 OScN, 62 C57BL/ l OScSn, 39 C57BL/ l OSn, 59 C57/L, 39 DBA/1, 39 DBA/2, 39, 55, 64, 80, 98, 114 DW/J, 43, 49, 156 GL,51, 157 HRS/J, 56-57, 84, 156 ICR/Jcl, 100 LG/J, 98-99 MRL/Mp, 38, 59, 60-62, 64, 91, 98-100, 121 MWT/Le, 82 NFR/N, 46, 49, 82 NFS/N, 64, 82 N:NIHS, 91 nomenclature for, 17, 34 NZB (New Zealand black), 64, 87, 112, 113, 122 NZW, 105 P/N, 64 RHJ/Le, 56 SB/Le, 42, 87, 93, 96, 97 SJL/J, 52, 59, 61, 62, 64, 87-88 SWR, 112 WB/Re, 82, 83 see also Reproduction Inbred rats (see also Table 2-1, p. 39) BBZ/Wor, 133 BN, 161 DA, 126 F344, 126, 163 LEW, 126, 161, 163 PVG, 126 WAG, 126 see also Reproduction Infectious agents clinically silent, 12- 13 depression of oncogenic virus genes, 13 effects of glucocorticoids on susceptibility to, 143 genetic mechanisms in resistance or susceptibility to, 161- 164 immunosuppression by, 12- 14 synergistic effects between, 13 X-linked resistance to, 163 see also specific agents Inflammatory response, 4, 9, 10, 221 Influenza A, 161 Insulin, 10, 14, 17, 43-45, 72, 100, 103, 130-134 239 Insulinopenia, 72 Insulitis, 100-101, 104, 131, 133 Interferons activation of NK cells with, 42, 119 defined, 224 ~y-, 9, 98, 111, 224 poly(A-U), 145- 146, 228 rat beta, 134 and resistance to infectious agents, 163 suppression by environmental agents, 11, 13 type I (cx/~), 63, 112 Interleukin (IL) diminished production of, 91 IL-1, 102, 223 IL-2, 9, 91, 102, 111, 143, 223, 225 IL-3, 223 IL-4, 9, 224 IL-5, 9 IL-6, 9, 98, 224 role in immune response, 9 Islet cells, defects in, 41, 73 Islets of Langerhans atrophy, 44, 72 degeneration of, 17 destruction of, 131 function of, 224 hypertrophy of, 17 transitional hyperplasia, 101 see also ~ cells Ixodid tick, 137 J Japanese B encephalitis virus, 147 K K virus, 13, 143 Ketonuria, 101 Kupffer cells, 8 L Lactic dehydrogenase virus (LDV), 12, 13, 161 Langerhans' cells diminished, 81 function of, 3, 8, 225 response to ultraviolet radiation, 145 Lead, immunosuppressive effects of, 11 141

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240 INDEX Leishmania donovani, resistance/ susceptibility mutants, 36, 37, 39-40 Leishmania major, survival mechanism, 40 Lentiviruses, 13 Leukocytes defects in, 41, 74, 76, 84, 126 peritoneal exudate, 41 Leukocytopenia, 58 Life span, short in mice, 65, 115-116 in rats, 126 see also Mutations, lethal Lipopolysaccharide (LPS) defined, 225 enhanced response to, 141 impaired response to, 17, 37, 62-64, 76, 84, 94, 96, 137 macrophage activation by, 95 Listeria monocytogenes, susceptibility to, 57,88, 127 Liver parenchymal cells, defects in, 41 Louping ill virus, 94 Lupus, discoid, 135 Lupus nephritis, 108, 113; see also Systemic lupus erythematosus Lymph node abnormalities enlargement, 47, 53-54, 59-60, 66, 87-88, 90, 91, 94 in folicle development, 84 hyperplasia, 84, 94, 97, 105, 110, 114 paracortical areas, 49, 126, 144 small, 50, 58, 77 Lymphadenectomy, 147 Lymphadenopathy, 47, 53-54, 59-60, 66, 87-88, 90, 91, 94 Lymphocyte abnormalities elevation of circulating lymphocytes, 47 decreased number (lymphopenia), 46, 50, 66, 72, 74, 77, 78, 110, 126, 131, 132, 225 diet-induced, 11 drug-induced, 12 in IL-2 production 54 lymph node, 46, 77, 126, 138 peripheral blood, 50, 227 self-directed cytotoxic lymphocytes, 61 splenic, 52, 68, 77, 84 thymic, 84, 126 Lymphocytes differentiation antigens, see Cell surface antigens follicular aggregates of, 105 peripheral blood, 50, 227 radiosensitivity, 145 receptors, 10, 60 repopulation of, 79 thymic-derived, 54 see also specific lymphocytes Lymphocytic choriomeningitis virus (LCMV), 12, 13, 14, 147 Lymphokine-activated killer cells, independence from NK cells, 93 Lymphokines depressed production of, 45 functions of, 7, 225 see also Interleukin Lymphomagenesis, 57, 71 Lymphomas autoimmune disease and, 106, 110, 114 defined, 225 follicle center cell, 102 genes affecting, 117 immunoblastic sarcoma, 138 nonthymic, 121 reticulum cell sarcomas, 71, 117- 119, 228 thymic, 57, 78 Lymphopoietic cells, abnormality in. 83 Lymphoproliferation, 37, 52-54, 59-62. 90-91, 105, 110, 141 Lymphosarcoma, 92 Lysosomal function, defects in, 42, 43 Lysosomal granules, giant, 41 M Macrophage defects, 41, 42 alveolar, 65, 141 chemotactic, 68 in control of pathogen replication, 40 diet-induced, l l function of, 225 LPS-induced, 63, 64 in mobilization and listericidal activity, 57 peritoneal, 68, 76, 129, 143 and resistance to tolerance induction, 80 splenic, 40, 68 in tumoricidal capacity, 63 Macrophages alveolar, 8 endogenously activated, 119, 120 functions of, 7, 8

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INDEX 24 1 monocyte, 3 Maintenance of immunodeficient rodents, see Husbandry practices Major histocompatibility complex (MHC) antigens and C5 deficiency, 55 Class I, 7, 9, 86, 105, 130, 219 Class II (Ia), 7-8, 9, 70, 118, 130, 142, 163, 220, 223 defect in expression of, 63, 105 and diabetes, 100-101, 130-131 expression of, 8 genetic locus, 114, 117, 130- 131 role of, 7, 226 structure of, 7-8 T-cell receptor allele associated with responsiveness to, 118 Mammary tumor viruses, 13 Mast cells antibody interaction with, 3, 10 cytoplasmic marker for, 42 defects in, 41, 83 function of, 8, 10, 225-226 Mating systems, see Reproduction Measles, 161 Melanocytes, 81, 83, 226 Melanoma, 73, 92 Membrane attack complex, 55, 226 Mice monoclonal antibodies reacting to cell surface antigens in, 213-215 strains, see Congenic mouse strains; Hybrid mouse strains; Inbred mouse strains; Outbred mouse strains stress in, 12 transgenic, 101 see also Mouse mutants Microphthalmia, 37, 51-52, 67-69, 73-77 Microwave irradiation, 145 Mink, Aleutian trait, 41 Minute virus of mice (MVM), 12 Mixed lymphocyte reactions (MLRs), 54, 104, 127, 145, 226 Moloney virus, 13 Monoclonal antibody Mel-14, 60 Mouse adenoviruses, 143 Mouse chromosomes, 6, 7, 18-31, 39, 40, 43, 46, 47, 49, 51, 52, 54, 55, 58, 62, 64, 68, 69, 72, 73, 75, 77, 82, 84, 85 89, 98, 100, 105, 112, 157, 162, 164 Mouse hepatitis virus (MHV), 12, 13, 96, 142, 143, 148, 162, 226 Mouse mutants (see also Table 2-1, pp. 37-38) ad (adipose), 43 Aw (white-bellied agouti), 42 b (brown), 43 Beg'? Bcgs (resistance/susceptibility to Mycobacterium bovis), 156 bg (beige), 15, 92-94' 96-97, 117, 156 ce (extreme dilution), 51 en (achondroplasia), 99 db (diabetes), 17, 72, 101, 157 Dh (dominant hemimelia), 93, 160 dl~ (downless-J), 157 dw (dwarf), 75, 156 ep (pale ears), 42, 43 gl (gray-lethal), 68, 157 gld (generalized lymphoproliferative disease), 90, 156 Hc (hemolytic complement absent), 156 hr (hairless), 156 Ityr, Itys (resistance/susceptibility to Salmonella typhimurium), 95-96, 156 le (light ear), 42 Ih (lethargic), 160 Ipr (lymphoproliferation), 52, 88, 99, 117, 156, 158 Lps'1 (lipopolysaccharide response, defective), 96, 156 Lshr, Lshs (resistance/susceptibility to Leishmania donovani), 36, 37, 39-40, 156 m (misty), 45, 157 me (motheaten), meV (viable motheaten), 159 mi (microphthalmia), 51, 76, 159 nu (nude), 1, 14, 57, 86, 95, 102, 107, 119-120, 126, 147, 151-152 nu xid, 86 ob (obese), 17, 101, 159 oc (osteosclerotic), 51, 68, 160 op (osteopetrosis), 51, 68, 160 pa (palid), 42, 43 pe (pearl), 42 rp (reduced pigmentation), 43 ru (ruby eye), 42 ru-2mr (maroon), 42 sa (satin), 42, 96-97 sa bg, 96-97 scid (severe combined immune deficiency), 14, 45, 156 Sl (steel), 120

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242 INDEX sit (slate), 40 Tol-1 (tolerance to gamma-globulin), 156 ~ (viable dominant spotting), 157 wi (whirler), 43 wst (wasted), 160 xid (X-linked immune deficiency, 54, 156 Yaa (Y-linked autoimmune accelerator), 97 Mouse thymic virus, 143 Mucosa-associated lymphoid tissue (MALT), 8, 225 Multinucleated giant cells, 53 Murine cytomegalovirus, 12 Murine leukemia viruses (MuLVs), 13, 57, 71, 78, 92, 115, 117, 119-120, 121, 222, 226 Murine pinworm (Syphacia obvelata), 14 Mutations advantages and disadvantages of, 15 allelic, 1, 36, 37, 39-40, 42, 43, 54-58, 62-71, 82, 125-126 antigen-selected somatic, 110 codominant/semidominant, 15, 67, 82, 220, 229 definition, 15, 226 lethal, 51-52, 84, 124-125, 156, 158, 159 maintenance of, 15-16; see also Reproduction modification of, 16 multiple, 1, 16, 44-45, 90-94 nomenclature for, 15, 17, 34 provirus integration into normal allele, 56 radiation-induced, 40, 42, 67 sex-linked, 85 single point, 1, 36-90 spontaneous, 15, 40, 43, 47, 51, 52, 58, 59, 64, 69, 72, 73, 75, 77, 80, 84, 123, 124, 128 see also Hamster mutants; Mouse mutants; Rat mutants Mycobacterium bovis, resistance/ susceptibility mutants, 36, 37, 39-40, 127 Mycobacterium lepraemurium, resistance/ susceptibility mutants, 36, 39-40 Mycoplasma pulmonis, 128, 163 Myocardial infarction, 60, 110 N Natural killer (NK) cells activation of, 42 depression of, 42, 43, 91-94, 102, 116, 119-120, 142, 146 increased activity, 70, 71, 73, 93, 126 independence from lymphokine-activated killer cells, 93 lack of, 104 role of, 10, 226 serotonin dependency of, 10 source of, 10 and tumor growth, 24, 92 Nematode infestation, resistance to, 83, 164 Neurological disorders, mouse mutants with, 42-43, 84 Neutrophils, see Polymorphonuclear leukocytes Nippostrongylus brasiliensis, 83 Nocardia (mitogen), diminished response to, 86 Nomenclature, 15, 17, 34 Nutrition, and immunosuppression, 144; see also Diet o Obesity, 17, 43-45, 72-73, 104 Oligodactyly, 47 Oncogenic virus genes, suppression of, 13 Oncornaviruses, immunosuppression by, 13, 227; see also specific viruses Osteoclasts cytoplasmic marker for, 42 defects in, 51, 68, 74, 76, 123, 124-125, 129 elevated acid phosphatase, 123 function of, 227 reduced acid phosphatase in, 51, 68, 76 Osteopetrosis defined, 227 in mice, 51-52, 67-69, 73-77 in rats, 123- 125 Osteoporosis, 116 Osteosclerosis, 73-74, 227 Outbred mice (see also Table 2-1, p. 39) sensitivity to ectromelia virus, 162 p Pancreatic lymphocyte infiltration, 131 Paracoccidioidomycosis, 163 Parasites, delayed expulsion of, 83 Paroviruses, 143 Pericytes, cerebral cortex, defects in, 41

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INDEX 243 Periodic acid-Schiff (PAS)-positive cells, 50 Peyer's patches absence of IgA-specific B-cell precursors from, 85 atrophy of, 144 function of, 8, 227 small, 58, 66, 84, 126 Phytohemagglutinin (PHA)-induced blastogenesis, 46, 227 Picryl chloride, contact sensitivity to, 81 Plaque-forming cell (PFC) responses, impaired, 46, 63, 227 Plasma cells, with Russell bodies, 66 Pneumococcal polysaccharide, failure to respond to, 85 Pneumocystis carinii, 79, 128, 142, 143, 153 Pneumocytes, type II, defects in, 41 Pneumonitis interstitial, 54, 60, 79 spontaneous, susceptibility to, 42, 128 Polyarteritis, 60, 99, 121 Polybrominated biphenyls, 140 Polydactyly, 47, 48 Polydipsia, 101, 131 Poly(A-U), 145- 146, 228 Poly(I-C), 119, 228 Polymorphonuclear leukocytes (PMNs) aggregates in skin, 65 antibody interaction with, 3 basophils, 10 cytoplasmic marker for, 42 decreased number of, 126 function of, 8, 228 impaired chemotactic and bactericidal activities, 41 -42, 141 increased number of, 47, 66 response to LPS, 63 see also Mast cells Polyomavirus, 147, 161 Polyphagia, 101 Polyunsat;urated fatty acids, 144 Polyuria, 101 Progenitor cell replication, model for cell- associated molecules limiting, 64-66 Prokaryotic cells, 4 Prolactin, 10, 46 Proliferative enteritis, 139 Propylgallate, 141-142, 227 Proteinuria, 91, 99, 110 Proximal tubule cells, defects in, 41 Pseudomonas aeruginosa, 144- 145 Purkinje cells, cerebellar, defects in, 41, 43, 84 Pyogenic bacteria, susceptibility of mutants to, 42 Pyramidal cells, defects in, 41 R Radiation, ionizing, and immunosuppression, 144- 145 Rat mutants (see also Table 2-1, p. 39) fa (fatty), 124, 133 op (osteopetrosis), 123 rnu (Rowett nude), 1, 14, 147 tl (toothless), 39, 123, 124, 128- 129 Rats adjuvant arthritis in, 14 immunoglobulins, 5 linkage map, 32-33 monoclonal antibodies reacting to cell surface antigens in, 213-215 stress in, 12 see also Inbred rats; Rat mutants Raucher virus, 13 Renal disease, 50, 54, 61, 66, 91, 94, 99, 108, 110, 112, 114, 121 Reovirus 3, 12, 14 Reproduction backcross linkage analysis, 63 backcrosses, 59, 64, 86-88, 99, 100-101, 126, 156-158, 160, 218 balanced stock, 156- 157, 219 brother x sister mating, 52. 87, 103, 121, 139, 155-156, 158, 159 cross-intercross cycles, 52, 59, 158-159, 160 diabetic mice, 45, 103, 157 double heterozygote repulsion mating, 157 heterozygous matings, 45, 47, 51, 67, 69, 73, 76, 83-85, 125, 128, 129, 156, 158 high-performance, 100 homozygous, 125, 156, 158 homozygous males and heterozygous females, 58, 71, 124, 128, 139 hybrid matings, 99 inbreeding, 62, 155- 159 without inbreeding, 159- 160 intercrossing, 156- 158, 224 outcrossing, 100

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244 INDEX ovarian transplantation method, 67, 73, 77, 85, 158-159, 160, 227 paired matings, 89, 98 random matings, 122, 123, 124 after thymus transplants, 125 transferring a mutation to a hybrid background, 159- 160 transferring a mutation to an inbred background, 59, 64, 86-88, 99, 100-101, 126, 156, 157-159 trio matings, 62 Reticuloendothelial system function of, 228 reduced function in, 88 stimulant, 146 Reticulum cell sarcomas, 71, 117- 119, 228 Retroviral genes, 44, 107 Retroviruses, see Murine leukemia viruses; Oncornaviruses Rickets, 74 Rickettsia akari, 163 Rickettsia tsutsugamushi, 163 S Salmonella choleraesuis, 137 Salmonella typhi, 40 Salmonella typhimurium absence of aroA gene, 96 impaired clearance from mucosal surfaces, 63 index of killing, 96 resistance to, 36, 37, 39-40, 96 susceptibility to, 36, 37, 39-40, 62-63, 95-96, 143 Sendai virus, 12, 13, 121, 128, 143, 148, 161, 162 Senescence, early, 115- 117 Serotonin and bactericidal activity of PMNs, 42 decreased levels in platelets, 42 function of, 10, 229 Serum amyloid A, 63, 229 Severe combined immunodeficiency, 14, 37, 45, 77-80, 85, 92 Sheep red blood cells (SRBCs) defined, 229 reduced immune response to, 46, 47, 49, 81, 84, 115, 116, 121, 141-142, 146 Shock, complement system activation and 9-10 Skin allograft rejection impaired ability for, 46, 58, 110, 119, 132 infectious agents and, 13 Spinal cord neurons, defects in, 41 Spleen, model of functional relationships with thymus and bone marrow, 93 Spleen transplantation correction of defects by, 68-69 transfer of syngeneic spleen cells, 146 Splenectomy, 147 Splenic abnormalities absence of B colonies, 94 asplenia, 47, 93 decreased lymphoid cells, 50 hyperplasia, 106, 110 periarteriolar sheaths, 126 perifollicular sheaths, 49 reduced cellularity, 51 small organ, 58, 77 splenomegaly, 54, 60, 65-66? 68, 87-88, 94, 97, 106, 229 stem cell increases, 68, 76 in T cells, 57, 125 ThB+ cells, 94 St. Louis encephalitis virus, 94 Staphylococcus aureus, delayed clearance of, 55 Starvation, 51 Stem cells depression of, 141 differentiation, 83 function of, 229 hematopoietic, 3, 141 radiosensitivity, 145 splenic, 51, 68, 76, 141 Sterility, 66, 82, 156, 158 Streptococcal group A carbohydrate (GAC), impaired response to, 95 Stress, and immunosuppression, 11 - 12, 142, 146 Submandibular gland, leukocyte infiltrates of, 104 Systemic lupus erythematosus, 54, 99, 105, 108-111, 114-115, 121, 122, 135, 229 T T cell defects absence of mature cells, 92-94 antibody response against erythrocytes, 107

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INDEX 245 ,B-chain, deletion in, 109 Tetrachlorodibenza-p-dioxin, 140, 229 bone marrow TdT+ cells, 66 Tetracyclines, 12 decreased number of cells, 46, 49, 66, Theiler's murine encephalomyelitis virus, 70-71, 126-127, 131, 132, 145 117, 163 deletion of VT-cell receptor genes, 118 hyperplasia, 91 increased number of cells, 47, 101 Ly- 1 + expansion, 91 in Ly-5 expression, 60 in Ly-123+ subset, 107 in lymph nodes, 53-54 lymphopenia, 45, 104, 145 in mitogen responses, 104, 125, 141 NTA-reactive antigen, 106 production of pathogenic IgG anti-DNA, 109 proliferation abnormality, 54, 57, 66, 78 response to I-region alloantigens, 57 splenic, 57 suppressor-inducer (Ts), 50, 102, 106, 119, 121, 144 Tc, 41, 42, 61, 66, 132 Th, 47, 57, 70, 112-113, 116, 119, 132, 141 in Thy-1 + populations, 63, 110, 113 T cells activation of, 7, 9, 70 CD4, 113 CD8, 113, 142 cytotoxic (Tc), 7, 9, 10, 41, 42, 70, 220; see also Natural killer cells differentiation, 7, see Cell surface antigens estrogen receptors, 10 function of, 3, 8, 9, 229-230 growth factors, 9; see also Interleukin helper-inducer (Th), 7, 9, 47, 57, 91, 142, 230 Ia antigen expression on, 8, 9 interaction with B cells, 3, 7, 9, 91, 92, 109, 112, 116, 119 macrophage activation by, 95 model for thymus-independent maturation of precursors to functional effecter cells, 127 proliferation of, 3, 7, 54 structure, 7 surface-membrane inserted antigen receptor (Ti), 7, 10 Ts, 9, 230 see also Lymphocytes Taenia teaniaformis, 164 Thrombocytes, elevation of, 47 Thymectomy, 146-147 Thymic defects absence of Ia+ cells, 70 athymia, 93, 138, 148 atrophy, 49-50, 57, 110, 142, 144 B-cell influx, 119 epithelial dysgenesis, 70 hyperplasia, 105, 110, 114 involution, 45, 51, 65, 105* 140 lymphomas, 57, 78, 79 reduced cellularity, 84 small organ, 58, 65, 77 Thymulin, 50, 105, 230 Thymus function of, 230 model of functional relationships with spleen and bone marrow, 93 see also Thymic defects Thyroid defects calcitonin-secreting cells, 74, 76 follicular cells, 41, 51 Hashimoto-like thyroiditis, 132, 133, 222 thyroiditis, 95 Thyrotropic hormone-producing cells, deficiencies in, 49 Thyroxine, 10 Tonsils, 8 Transmissible ileal hyperplasia, 139 Trichinella spiralis, 83, 147, 164 Trichuris muris, 164 Tris, 140 Tumor growth and metastasis anesthetic agents and, 12 models for, 69-71, 92 NK cell activity and, 92 Tumors and tumor cell lines B16F10, 92 CEM, 92 contaminants in, 12 human, 92 immunosuppression by, 146 impaired cytolysis of, 42 K562, 92 LOX, 92 murine, 92 ovarian granulosa cell tumors, 92 reticulum cell neoplasms, 99

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246 INDEX suppression of, 13 YAC-1, 92 Tyzzer's disease, 128 U Ultraviolet radiation, and immunosuppression, 145, 230-231 V Variable-region-coding elements, aberrant deletions of, 78 Vascular disease, 97, 110 Vasculitis, 135, 114, 222 W Wasting disease, 71, 84-85 Water, hyperchlorinated acidified, 11, 152-153 X Xenografts, 79, 231