Valerie E. Jones

Bio: Valerie E. Jones is an academic researcher from National Institute for Medical Research. The author has contributed to research in topics: Nippostrongylus brasiliensis & Immunity. The author has an hindex of 11, co-authored 15 publications receiving 711 citations.

Protective immunity to Nippostrongylus brasiliensis in the rat. III. Modulation of worm acetylcholinesterase by antibodies.

Abstract: Antibodies to Nippostrongylus brasiliensis acetylcholinesterase were found in sera from infected rats and in one pooled sample were associated with IgG1. Antibodies were formed against all three isoenzymes of worm acetylcholinesterase and antisera taken from animals which had experienced multiple infections had the strongest activity, in particular to isoenzyme A. No antibodies were found against the worms' non-specific esterases, aminopeptidases or acid phosphatases. It appeared that acetylcholinesterase production by the worms was increased in the presence of antibodies and decreased in their absence. The evidence for this conclusion is as follows. First, adapted worms, which are found in rats with high levels of antibodies to all three isoenzymes, had an increased production of these isoenzymes. However, when these adapted worms were transferred to non-immune rats, their production of isoenzyme A was rapidly reduced. Secondly, in rats passively immunized with antiserum containing antibodies to acetylcholinesterase, the worms had increased levels of this enzyme. Thirdly, cortisone treatment of immune rats completely prevented immunity from acting on the worms; the acetylcholinesterase production of these worms was low compared with adapted worms from untreated immune rats and was similar to that of normal worms from non-immune rats. These experiments provide evidence that antibodies to this enzyme are one factor which modulates acetylcholinesterase production by this nematode.

Protective immunity to Nippostrongylus brasiliensis: the sequence of events which expels worms from the rat intestine.

Abstract: In these experiments, adult Nippostrongylus brasiliensis worms were damaged by protective antibodies in either actively or passively immunized rats. These damaged worms were then transplanted into the intestines of normal recipient rats, from which they were rapidly expelled. The rapid expulsion of damaged worms from normal recipients was an active process because when recipients were irradiated, the damaged worms were not expelled. Furthermore, when irradiated recipients were given protective antibodies as well as damaged worms they were still unable to expel the damaged worms. The active expulsion mechanism present in normal rats seems unlikely to be a specific immunological event because treatment of recipients with anti-lymphocytic serum (ALS) did not mimic the effect of irradiation. That is, ALS treatment did not prevent the expulsion of the damaged worms although it suppressed the induction of active immunity. These experiments show that, when immunity acts to expel adult worms from the rat small intestine, two separate and sequential steps which do not require complement are involved: (1) The initial and essential first step is the action of protective antibodies on the worms. In this process the worms are damaged; changes occur in some enzymes and the structure of their gut cells deteriorates. Once these antibody-induced changes have occurred, they are irreversible and the damaged worms are susceptible to the second step. (2) The second step expels the worms. It acts completely independently of the presence of protective antibodies but cannot act unless step (1) has already occurred. The factors involved are present in normal rats. In this report, no evidence of the nature of this step is presented except that it is prevented by irradiation and slightly affected by ALS treatment. If the release of pharmacologically active amines from mast cells is important in immunity, as suggested by other workers, it would be involved in this step. This work refutes the `leak lesion' hypothesis for worm expulsion. The `leak lesion' hypothesis proposed that, in order for protective antibodies to affect the worms, the intestinal mucosa had first to be damaged by a local anaphylactic reaction and that worm expulsion was the direct consequence of the action of protective antibodies on the worms. It is now clear that the action of protective antibodies alone cannot cause the worms to be expelled and that, if anaphylaxis is involved, its action is subsequent to the antibody-mediated damage to the worms.

The circulating immunoglobulins involved in protective immunity to the intestinal stage of Nippostrongylus brasiliensis in the rat.

Abstract: Antisera taken from rats after one, two or three larval infections with Nippostrongylus brasiliensis or after one infection of adult worms were separated by chromatography and the fractions were tested for passive protective activity. Irrespective of the number or type of infections given, protection against the parasite was most frequently obtained with fractions of antisera containing predominantly 7Sγ1-globulin. γM- and γA-globulins sometimes appeared to contribute to protective activity, but γM-globulin was not the major source of protective antibodies in antisera taken after a primary infection either of adult worms or of larvae. 7Sγ2-protective antibodies were found only in a pool of antiserum taken after three infections. Rats were passively protected with antiserum or fractions of antiserum, which were free of reagins and of other identifiable anaphylactic antibodies. It appears that rats can be passively immunized with antisera which do not have anaphylactic activity.

Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice.

Abstract: When rodents are infected with the nematode Nippostrongylus brasiliensis, large numbers of eosinophils appear in their blood and lungs and their serum immunoglobulin E (IgE) is increased. Injection of a monoclonal antibody to interleukin-5 completely suppressed the blood eosinophilia and the infiltration of eosinophils in the lungs of parasitized mice but had no effect on serum IgE. In contrast, an antibody to interleukin-4 inhibited parasite-induced IgE but not the eosinophilia. These results show that interleukin-5 is important in eosinophil production in vivo and that IgE and eosinophil production are regulated by different cytokines produced by the TH2 subset of CD4-expressing T cells.

Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice.

Abstract: Parasitic helminths typically induce components of immediate-type hypersensitivity, including elevated serum IgE, eosinophilia, and mucosal mast cells. These responses are T-cell-dependent and associated with rapid expulsion of parasitic worms from a sensitized host; existing experimental systems have failed to define the precise role of cytokines in these responses. We report here that anti-interleukin 4 or anti-interleukin 4 receptor antibodies block the polyclonal IgE response to a parasitic nematode, Heligmosomoides polygyrus, and abrogate protective immunity to the infection. In contrast, anti-interleukin 5 antibody prevented H. polygyrus-induced eosinophilia but did not prevent protection. These data provide evidence that a specific cytokine affects the physiology and survival of a parasitic nematode in the host.

Trichinella and Trichinosis

Abstract: 1 Historical Introduction.- 1. Prologue: Ghosts of Christmas Past and Christmas Present.- 2. A Worm Discovered (1835).- 3. A Nematode Life Cycle Discovered (1835-1860).- 4. From Zoological Curiosity to Lethal Pathogen (1860-1900).- 5. Consequences (Politics and Parasites).- 6. The Recent Past.- References.- 2 Species, and Infraspecific Variation.- 1. Historical Perspective.- 2. A Working Definition of Species.- 3. Terminology.- 4. Distribution of Isolates.- 5. Criteria for Species and Isolates.- 5.1. Genetic Criteria.- 5.2. Morphological Criteria.- 5.3. Biochemical and Immunological Criteria.- 5.4. Sensitivity to Drug Treatment.- 5.5. Effect of Host on Reproductive-Capacity Index.- 5.6. Other Biological Characteristics.- 6. Trichinella spiralis var. pseudospiralis-an Enigma.- 7. Speciation in Trichinella.- 8. Future Considerations.- References.- 3 Biology.- 1. Introduction.- 2. Ingestion of the Infective First-Stage Larva.- 3. Digestion of Host Tissues away from the Infective First-Stage Larva.- 4. Intramulticellular Enterai Niche.- 4.1. Entrance of the Infective First-Stage Larva.- 4.2. Molting and Development.- 4.3. Mating.- 4.4. Fecundity.- 5. Intracellular Parenteral Niche.- 5.1. Migration of the First-Stage Larva to the Niche.- 5.2. Entrance of the Migratory First-Stage Larva.- 5.3. Growth and Development.- 5.4. Mature Nurse Cell-Infective First-Stage Larva Complex.- References.- 4 Biochemistry.- 1. Introduction.- 2. Carbohydrates and Carbohydrate Metabolism.- 2.1. Adult Worms.- 2.2. Muscle Larvae.- 3. Respiration.- 3.1. Adult Worms.- 3.2. Muscle Larvae.- 4. Lipids and Lipid Metabolism.- 4.1. Adult Worms.- 4.2. Muscle Larvae.- 5. Nucleic Acids and Nucleic Acid Metabolism: Muscle Larvae.- 6. Proteins and Protein Metabolism: Muscle Larvae and Adult Worms.- 7. Nutrition.- 7.1. Adult Worms.- 7.2. Muscle Larvae.- References.- 5 Anatomical Pathology.- 1. Introduction.- 2. Gastrointestinal Tract.- 2.1. Gross Changes.- 2.2. Microscopic Changes.- 3. Striated Muscle.- 3.1. Gross Changes.- 3.2. Microscopic Changes.- 3.3. Encapsulation.- 3.4. Calcification.- 4. Other Organs Involved.- 4.1. Heart.- 4.2. Liver.- 4.3. Spleen.- 4.4. Kidneys.- 4.5. Eyes.- 4.6. Lungs.- 4.7. Central Nervous System.- 4.8. Bone Marrow.- 4.9. Other Locations.- References.- 6 Pathophysiology of the Gastrointestinal Phase.- 1. Format of This Review.- 2. Gastrointestinal Symptoms.- 3. Morphological Changes.- 3.1. Macroscopic.- 3.2. Histological.- 4. Physiological Changes.- 4.1. Epithelium-Related.- 4.2. Smooth-Muscle-Related.- 5. Bases for Functional Changes.- 5.1. Direct Action of Parasite.- 5.2. Influence of Lamina Propria.- 5.3. Endocrine Disturbances.- 6. Host-Parasite Interrelationships.- 7. Relationships between Pathophysiology and Symptoms.- 8. Summary.- References.- 7 Pathophysiology of the Muscle Phase.- 1. Introduction.- 2. Parasite-Induced Modifications in Host Striated Skeletal Muscle.- 2.1. Alterations Induced in the Host Myofiber during Contact and Entry by the Newborn First-Stage Larva.- 2.2. Alterations in Host Muscle during Growth and Development of the Muscle Larva.- 2.3. Mature Nurse Cell.- 2.4. Hypothesis: A Possible Mechanism by Which the Parasite Initiates Redifferentiation in the Host Myofiber.- 2.5. Benefits Derived by the Muscle Larva from Pathophysiological Alterations in Host Muscle.- 3. Cardiopathophysiology in Trichinosis.- References.- 8 The Immune Response.- 1. Introduction.- 2. Immunity and the Intestinal Phase.- 2.1. Immunity against Adult Worms in Primary Infections.- 2.2. Immunity against Adult Worms in Reinfections.- 2.3. Immunity against Preadult Stages-Rapid Expulsion.- 3. Immunity and Newborn Larvae.- 3.1. Active Immunity in Mice and Rats.- 3.2. Passive Immunity in Mice.- 3.3. Effects of Cells and Serum Components in Vitro.- 4. Genetic Influences on Immunity to Trichinella.- 5. Stage Specificity of the Immune Response.- 5.1. "Dual-Antibody" Hypothesis of Oliver-Gonzalez.- 5.2. Immunological Evidence.- 5.3. Parasitological Evidence.- 5.4. A Revision of the Dual-Antibody Hypothesis.- References.- 9 Antigens.- 1. Introduction.- 2. Source of Antigens.- 2.1. Cuticular Antigens.- 2.2. Excretory-Secretory Antigens.- 2.3. Somatic Antigens.- 3. Enumeration, Isolation, and Characterization of Antigens.- 4. Concluding Remarks.- References.- 10 Chemotherapy.- 1. Introduction.- 2. Experimental Chemotherapy.- 2.1. Methods.- 2.2. Drug Efficacy.- 3. Clinical Chemotherapy.- 3.1. Clinical Prophylaxis.- 3.2. Clinical Therapy (Treatment of Patent Infections).- References.- 11 Clinical Aspects in Man.- 1. Introduction.- 2. Infection and Disease.- 2.1. Proportion of Symptomatic and Asymptomatic Cases in Trichinosis.- 2.2. Course of Trichinosis.- 2.3. Severity of Trichinosis.- 2.4. Factors That Influence the Severity of Trichinosis.- 3. Symptoms, Signs, and Clinical Pathology.- 3.1. Abdominal Syndrome.- 3.2. General Trichinosis Syndrome.- 3.3. Signs of Allergic Vasculitis.- 3.4. Symptoms and Signs Associated with Muscle Tissue.- 3.5. Signs of Metabolic Disorders.- 3.6. Complications of Trichinosis.- 3.7. Pathology in Laboratory Tests.- 4. Diagnosis.- 4.1. Clinical History-Taking.- 4.2. Physical Examination.- 4.3. Paraclinical Tests.- 4.4. Finding the Parasite.- 4.5. Differential Diagnosis of Trichinosis.- 5. Management and Treatment.- 5.1. Treatment of the Intestinal Infection.- 5.2. Acute Severe Trichinosis.- 5.3. Moderate or Mild Trichinosis.- 5.4. Late and Convalescent Phases of Trichinosis.- 5.5. Trichinosis in Children, Pregnant and Lactating Women, and Immunosuppressed Patients.- References.- 12 Immunodiagnosis in Man.- 1. Introduction.- 2. Immunodiagnostic Methods.- 2.1. Parasite Antigens.- 2.2. Indirect Immunofluorescence.- 2.3. Passive Hemagglutination.- 2.4. Enzyme-Linked Immunosorbent Assay.- 2.5. Counterimmunoelectrophoresis.- 2.6. Other Serological Methods.- 2.7. Skin Tests.- 3. Evaluation and Recommendation.- 4. Conclusions.- 5. Protocols for Indirect Immunofluorescence and Enzyme-Linked Immunosorbent Assay.- 5.1. Indirect Immunofluorescence.- 5.2. Enzyme-Linked Immunosorbent Assay.- References.- 13 Epidemiology I: Modes of Transmission.- 1. Introduction.- 2. Sylvatic Cycle.- 3. Domestic Cycle.- 4. Special Epidemiological Circumstances.- 5. Susceptible Host Species.- References.- 14 Epidemiology II: Geographic Distribution and Prevalence.- 1. Introduction.- 2. North America.- 2.1. Canada and Alaska.- 2.2. Greenland.- 2.3. United States.- 2.4. Latin America.- 3. Europe.- 3.1. British Isles.- 3.2. Germany.- 3.3. Austria.- 3.4. Switzerland.- 3.5. The Netherlands.- 3.6. Belgium.- 3.7. France.- 3.8. Spain.- 3.9. Portugal.- 3.10. Italy.- 3.11. Greece.- 4. Scandinavia.- 4.1. Norway.- 4.2. Sweden.- 4.3. Denmark.- 4.4. Finland.- 5. Eastern Europe.- 5.1. Poland.- 5.2. Czechoslovakia.- 5.3. Hungary.- 5.4. Romania.- 5.5. Yugoslavia.- 5.6. Bulgaria.- 6. Union of Soviet Socialist Republics.- 7. Asia.- 7.1. Middle East.- 7.2. Southeast Asia.- 7.3. Far East.- 8. Africa.- 9. Australia, New Zealand, and Pacific Islands.- References.- 15 Control I: Public-Health Aspects (with Special Reference to the United States).- 1. Introduction.- 2. Mechanisms of Control.- 2.1. Prevention of Swine Infections.- 2.2. Detection of Infected Swine.- 2.3. Rendering Infected Pork Noninfective.- 2.4. Game Foods.- 3. Measures Adopted in the United States.- 3.1. Control of Garbage.- 3.2. Regulation of Commercial Pork Products.- 3.3. Game Foods.- 3.4. Education.- 3.5. The Future.- References.- 16 Control II: Surveillance in Swine and other Animals by Muscle Examination.- 1. Introduction.- 1.1. General Methods and Uses.- 1.2. Criteria for Use.- 2. Trichinoscopic Method.- 2.1. Use.- 2.2. Procedure for Swine Diagnosis.- 2.3. Drawbacks.- 2.4. Other Uses.- 3. Basic Digestion Method.- 3.1. Basic Procedure.- 3.2. Modifications.- 3.3. Advantages and Disadvantages.- 4. Pooled Digestion Methods.- 4.1. Pooled-Sample Method: Procedure.- 4.2. Stomacher Method: Procedure.- 4.3. Other Modifications.- 5. Other Direct Diagnostic Methods.- 5.1. Mechanical Disintegration Method.- 5.2. Microscopic Section (Biopsy Method).- 5.3. Xenodiagnosis.- 6. Summary.- References.- 17 Control III: Surveillance in Swine by Immunodiagnostic Methods.- 1. Introduction.- 2. Serological Methods.- 2.1. Complement-Fixation Test.- 2.2. Particle-Agglutination Methods.- 2.3. Indirect Immunofluorescence Test.- 2.4. Enzyme Immunoassays.- 2.5. Radioimmunoassay.- 3. Sensitivity and Specificity.- 4. Antigen Preparation and Purification.- 5. Evaluation of Serological Methods in Various Geographic Areas.- 5.1. Evaluation of the Enzyme-Linked Immunosorbent Assay in the United States.- 5.2. Evaluation of the Enzyme-Linked Immunosorbent Assay in European Countries.- 6. Mechanization.- 6.1. Mechanized System for the Macro-Enzyme-Linked Immunosorbent Assay.- 6.2. Mechanized System for the Micro-Enzyme-Linked Immunosorbent Assay.- 7. Surveillance by Serological Methods.- 7.1. Inspection at the Slaughterhouse.- 7.2. Inspection at the Farm.- 7.3. Individual vs. Population Control.- 7.4. Legislation.- 8. Concluding Remarks.- References.- Appendix 1 Synopsis of Morphology.- 1. Introduction.- 2. Morphology of the Adult Male.- 3. Morphology of the Adult Female.- 4. Morphology of the Infective First-Stage Larva.- References.- Appendix 2 Laboratory Techniques.- Methods.- References.

Chitinase and Fizz family members are a generalized feature of nematode infection with selective upregulation of Ym1 and Fizz1 by antigen-presenting cells

Abstract: Ym1 and Fizz1 are secreted proteins that have been identified in a variety of Th2-mediated inflammatory settings. We originally found Ym1 and Fizz1 as highly expressed macrophage genes in a Brugia malayi infection model. Here, we show that their expression is a generalized feature of nematode infection and that they are induced at the site of infection with both the tissue nematode Litomosoides sigmodontis and the gastrointestinal nematode Nippostrongylus brasiliensis. At the sites of infection with N. brasiliensis, we also observed induction of other chitinase and Fizz family members (ChaFFs): acidic mammalian chitinase (AMCase) and Fizz2. The high expression of both Ym1 and AMCase in the lungs of infected mice suggests that abundant chitinase production is an important feature of Th2 immune responses in the lung. In addition to expression of ChaFFs in the tissues, Ym1 and Fizz1 expression was observed in the lymph nodes. Expression both in vitro and in vivo was restricted to antigen-presenting cells, with the highest expression in B cells and macrophages. ChaFFs may therefore be important effector or wound-repair molecules at the site of nematode infection, with potential regulatory roles for Ym1 and Fizz1 in the draining lymph nodes. Macrophages are a fundamental feature of chronically inflamed tissue. In the course of long-term inflammation, the macrophage phenotype often shifts away from a highly microbicidal state towards an “alternative activation” pathway as the T-cell cytokine profile shifts from type 1 to type 2 (16). In the case of helminth infection or allergy, the type 2 response can dominate from the outset. Although our understanding of macrophage activation under these type 2 conditions is increasing, whether macrophages promote the disease state or protect against it remains essentially unknown. We and others have recently discovered that macrophages activated by type 2