Interleukin-8 (IL-8), a member of the C-X-C chemokine subfamily, is an important chemoattractant and cellular activator. This study was conducted to determine the role of IL-8 in the immunopathogenesis of HIV-I disease and tuberculosis. The first section involved determining the effect of infection with HIV-1, Mycobacterium tuberculosis and co-infection with both of these organisms on IL-8 j_ roduction in vivo. This was monitored by the determination of levels of serum or plasma EL-8 and peripheral cell-associated IL-8, assessing peripheral mononuclear (PBMC) and polymorphonuclear (PMN) cell capacity to produce IL-8 spontaneously or in response to various stimuli, and the detection of constitutive IL-8 mKNA expression in purified subsets of mononuclear cells. Results show that whereas there is evidence of detectable levels of cell-associated EL-8 (mKNA and protein) in peripheral cells of healthy individuals, this is largely lost in the disease states studied. Coupled with this was significantly increased circulating levels of EL-8 in serum and plasma found in HIV-1 infected individuals with or without concomitant pulmonary TB. On the other hand, the capacity of PBMC to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients and many of the HFV/TB group, but their corresponding capacities to respond to various stimuli was significantly diminished when compared to that of the normal donors. The release of IL-8 from PMN in the presence of an agonist was diminished mainly in individuals with pulmonary TB, which was further exacerbated by the presence of HIV-1 infection. HIV-1-infected individuals have an increased incidence of bacterial infections which could be related to defective functioning of PMN. The second section was aimed at detecting PMN abnormalities in HIV and I-HV/TB patients by monitoring EL-8-induced p-glucuronidase release and PMN chemotaxis in response to IL-8. IL-8-induced (I-glucuronidase release from PMN of normal individuals and TB patients occurred in a dose-dependent manner. In contrast, PMN from HTV-1 infected individuals, whether co-infected with M tuberculosis or not, showed a reciprocal response in that increasing IL-8 concentrations resulted in decreased enzyme release. This reciprocal slope of the IL-8 dose-response curve was altered for the majority of HIV-1 positive individuals tested irrespective of their CD4+ cell counts. In addition, PMN chemotaxis in response to IL-8 was also found to be significantly impaired in a group of HIV-1 infected patients coinfected w ithM tuberculosis when compared to healthy individuals. The third section of the study involved analysing the expression of the PMN cell surface markers, FcyRIII (CD 16), and the two human IL-8 receptors, designated IL -8RA and 1L-8RB. FcyRIII (CD 16) expression on the surface of PMN was significantly reduced in HIV-1 seropositive patients with pulmonary tuberculosis when compared to those individuals with either disease alone or healthy blood donors. A significant reduction in the percentage of PMN expressing IL-8RA and IL-8RB and in their respective fluorescence intensities was found in TB, HIV, and HTV/TB groups when compared to that obtained for the ND group. IL-8RA intensity of fluorescence was significantly decreased in the HTV/TB group when compared to the TB and HIV groups indicating a further down-regulation of IL-8RA expression owing to dual infection. On the other hand, IL-8RB fluorescence intensity was substantially reduced on PMN from patients with pulmonary TB and to a greater degree in those patients co-infected with HIV-1 and M. tuberculosis. Having found a reduction in the expression of both IL-8 receptors on PMN in all the infection groups, cellular events following the binding of IL-8 to IL-8 receptors on PMN isolated from dually infected patients, the group which showed the greatest reduction in IL-8 expression was analysed. Results indicated that the impairment of DL-8-dependent PMN functions such as degranulation and chemotaxis was associated with the reduced expression of IL-8 receptors on these cells. Increased circulating levels of IL-8 in HIV-1 infection and a diminished cellular capacity to produce IL-8 as shown in this study may have important implications for antimicrobial defences and normal immune processes. A dysregulated production of IL-8 in vivo is likely to play a role in the pathogenesis of HIV-1 disease, pulmonary tuberculosis, and dual infections with both organisms. In addition, cellular responses dependent on specific receptor engagement and the subsequent translation of signal transducing events that lead to phagocyte effector functions are clearly impaired in IL-8 receptor deficient phagocytes. Abnormal PMN functioning in HTV-1 infected individuals, as shown here by defective degranulation and chemotactic responses, have important implications in the pathogenesis of HIV-1 infection in terms of their ability to clear secondary microbial infections. Future attempts should be aimed at defining the mechanisms that bring about these changes in order to contribute to a greater understanding of the mechanisms that lead to an enhanced risk of superinfections in immunosuppressed individuals.

by Koo Sze Tak. / Thesis (M.Ph.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 148-165.

by Yeung Shing On. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1989 / Bibliography: leaves 91-112.

Lee Ka Wai Sharon. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 227-260). / Abstracts in English and Chinese. / ACKNOWLEDGEMENTS --- p.I / ABBREVIATIONS --- p.III / ABSTRACT --- p.VI / 摘要 --- p.XI / CONFERENCE PUBLICATIONS --- p.XVII / TABLE OF CONTENTS --- p.XVIII / Chapter Part I - --- General Introduction / Chapter Chapter 1: --- Introduction --- p.1 / Chapter 1.1. --- The Search of Immunomodulatory Agents --- p.1 / Chapter 1.2. --- Cordyceps sinensis (Dong Cong Xia Cao) as an Immunomodulatory Agent --- p.2 / Chapter 1.2.1. --- General Aspects --- p.2 / Chapter 1.2.2. --- Evidence from the Traditional Chinese Medicine Concepts --- p.2 / Chapter 1.2.3. --- Evidence from the Traditional Chinese Medicine Classics --- p.4 / Chapter 1.2.4. --- Evidence from the Modern Research Literature --- p.4 / Chapter 1.2.4.1. --- lmmunomodulation --- p.4 / Chapter 1.2.4.2. --- Anti-tumor Effects --- p.7 / Chapter 1.2.4.3. --- Other Activities Related to the Immune System --- p.8 / Chapter 1.2.4.4. --- Potential Active Ingredients: Cordycepin and Polysaccharides --- p.8 / Chapter 1.2.5. --- Prescription and Usage: Single Vs Concocted --- p.11 / Chapter 1.2.5.1. --- Single Form as an Immunoactivating Agent --- p.11 / Chapter 1.2.5.2. --- Concocted as an Anti-asthmatic Agent --- p.12 / Chapter 1.3. --- Our Hypothesis and Rationale --- p.13 / Chapter Chapter 2: --- Experimental Design --- p.24 / Chapter 2.1. --- General Aspects of the Human Immune System --- p.24 / Chapter 2.2. --- Designing the In vitro Study on Cell-mediated Immunity --- p.24 / Chapter 2.2.1. --- T Cells --- p.25 / Chapter 2.2.2. --- Macrophages --- p.26 / Chapter 2.3. --- Designing the In vitro and In vivo Study of Anti-tumor Activities --- p.29 / Chapter 2.3.1. --- Tumor Biology --- p.29 / Chapter 2.3.2. --- Tumor and Immunity --- p.29 / Chapter 2.3.2.1. --- T-Cell-Mediated Cytolysis (Tc Cells) --- p.30 / Chapter 2.3.2.2. --- Delayed-Type Hypersensitivity (TDth Cells) --- p.30 / Chapter 2.3.2.3. --- Natural Killer (NK) Cells --- p.30 / Chapter 2.3.2.4. --- Lymphokine-Activated Killer (LAK) Cells --- p.31 / Chapter 2.3.2.5. --- Antibody-Dependent Cell-Mediated Cytotoxic (ADCC) Cells --- p.31 / Chapter 2.3.2.6. --- Activated Macrophages (AMΦ) --- p.31 / Chapter 2.3.3. --- Mechanism of Tumor Engulfment --- p.32 / Chapter 2.3.4. --- The Experimental Plan --- p.33 / Chapter 2.4. --- Designing the In vitro Study and Clinical Trials on Anti-asthmatic Activities --- p.36 / Chapter Part II - --- Methodology / Chapter Chapter 3: --- Materials and Methods / Chapter 3.1. --- List of Materials and Their Origin --- p.39 / Chapter 3.1.1. --- Traditional Chinese Medicine --- p.39 / Chapter 3.1.2. --- Cells for In vitro Experiments --- p.39 / Chapter 3.1.3. --- Mice for In vivo Experiments --- p.40 / Chapter 3.1.4. --- "Medium, Buffer, Supplements and Reagents for Cell Culture" --- p.40 / Chapter 3.1.5. --- Dye for Cellular Staining --- p.40 / Chapter 3.1.6. --- Cell Mitogens and Activator --- p.41 / Chapter 3.1.7. --- Reagents for Flow Cytometric Analysis --- p.41 / Chapter 3.1.8. --- Reagent Kits --- p.41 / Chapter 3.1.9. --- ELISA Kits --- p.42 / Chapter 3.1.10. --- Antibodies --- p.43 / Chapter 3.1.11. --- Reagents for RNA Extraction --- p.44 / Chapter 3.1.12. --- Reagents for Gel Electrophoresis --- p.44 / Chapter 3.1.13. --- Reagents for cDNA Expression Array --- p.44 / Chapter 3.1.14. --- Other Reagents --- p.45 / Chapter 3.1.15. --- Special Equipment and Apparatus --- p.45 / Chapter 3.2. --- Details of Materials --- p.46 / Chapter 3.2.1. --- Traditional Chinese Medicine --- p.46 / Chapter 3.2.1.1. --- Natural Cordyceps sinensis --- p.46 / Chapter 3.2.1.2. --- HERBSnSENSEŚёØ Cordyceps --- p.46 / Chapter 3.2.1.3. --- Wheeze-Relief Formula --- p.46 / Chapter 3.2.2. --- "Media, Supplements and Reagents for Cell Culture" --- p.47 / Chapter 3.2.2.1. --- Cell Culture Media --- p.47 / Chapter 3.2.2.2. --- Serum Supplements --- p.47 / Chapter 3.2.2.3. --- Anti-CD16 Magnetic Microbeads --- p.47 / Chapter 3.2.2.4. --- Fico´HёØ-Paque Plus Solution --- p.47 / Chapter 3.2.2.5. --- PercolĺёØ Solution --- p.48 / Chapter 3.2.2.6. --- Phosphate Buffered Saline (PBS) --- p.48 / Chapter 3.2.2.7. --- Water --- p.48 / Chapter 3.2.3. --- Dye for Cellular Staining --- p.48 / Chapter 3.2.3.1. --- HemacoloŕёØ for Microscopy --- p.48 / Chapter 3.2.3.2. --- Trypan Blue Dye --- p.49 / Chapter 3.2.4. --- Reagents for Flow Cytometry --- p.49 / Chapter 3.2.4.1. --- FACS Flow Sheath Fluid --- p.49 / Chapter 3.2.4.2. --- FACS Wash Medium --- p.49 / Chapter 3.2.4.3. --- Paraformaldehyde --- p.49 / Chapter 3.2.5. --- Special Equipments and Apparatus --- p.49 / Chapter 3.2.5.1. --- Magnetic Cell Sorting System (MACS) --- p.49 / Chapter 3.3. --- Human Subjects --- p.51 / Chapter 3.3.1. --- Inclusion Criteria --- p.51 / Chapter 3.3.2. --- Exclusion Crtieria --- p.51 / Chapter 3.3.3. --- Medication --- p.52 / Chapter 3.3.4. --- Informed Consent and Patient Information --- p.52 / Chapter 3.4. --- Animals --- p.53 / Chapter 3.4.1. --- Maintenance --- p.53 / Chapter 3.4.2. --- Survival Experiment Using Erhlich Ascites Tumor Bearing ICR Mice --- p.53 / Chapter 3.4.3. --- Experiments of Immunomodulatory activity in Sarcoma 180 Bearing BALB/c Mice --- p.54 / Chapter 3.5. --- Methodology --- p.55 / Chapter 3.5.1. --- Preparation of the Traditional Chinese Medicine --- p.55 / Chapter 3.5.1.1. --- Hot Water Extraction of Water Soluble Fraction of Natural Cordyceps sinensis --- p.55 / Chapter 3.5.1.2. --- Hot Water Extraction of Water Soluble Fraction of HERBSnSENSEŚёØ Corydceps and the Wheeze-relief Formula for In vitro Experiments --- p.55 / Chapter 3.5.1.3. --- HERBSnSENSEŚёØ Corydceps for the In Vivo Experiments --- p.56 / Chapter 3.5.1.4. --- Extraction Efficiency of the Hot Water Extracts --- p.56 / Chapter 3.5.2. --- Limulus Ameobocyte Lysate Test --- p.56 / Chapter 3.5.3. --- Cell Preparation --- p.57 / Chapter 3.5.3.1. --- "Isolation of Human Peripheral Blood Mononuclear Cells, Lymphocytes and Monocytes" --- p.57 / Chapter 3.5.3.2. --- Isolation of Eosinophils --- p.58 / Chapter 3.5.3.3. --- Isolation of Spleen Cells from BALB/c Mice --- p.58 / Chapter 3.5.3.4. --- "Murine Ehrlich Ascites Tumor (EAT), PU5-18, and Sarcoma 180 (SC-180) Cell Lines" --- p.59 / Chapter 3.5.3.5. --- Human Eosinophilic Leukemic Cell Line (EoL-1) --- p.59 / Chapter 3.5.3.6. --- Human Hepatocarcinoma Hep-3B Cell Line --- p.59 / Chapter 3.5.3.7. --- Human Leukemic Cell Line (HL-60) --- p.59 / Chapter 3.5.3.8. --- Human Mast Cell Line (HMC-1) --- p.60 / Chapter 3.5.4. --- Collection of Mouse Serum and Human Plasma --- p.60 / Chapter 3.5.5. --- Collection of Culture Supernatant --- p.60 / Chapter 3.5.6. --- The Trypan Blue Exclusion Assay --- p.61 / Chapter 3.5.7. --- Colorimetric 5-bromo-2'-deoxyuridine (BrdU) Cell Proliferation Enzyme Linked Immunosorbent Assay (ELISA) --- p.61 / Chapter 3.5.8. --- Immunophenotyping --- p.62 / Chapter 3.5.9. --- The Cytometric Bead Array (CBA) Kits --- p.62 / Chapter 3.5.10. --- Intracellular Florescence Staining for Reactive Oxygen Species --- p.63 / Chapter 3.5.11. --- The Intracellular Zymosan Florescence Assay --- p.64 / Chapter 3.5.12. --- Total Cellular RNA Extraction --- p.64 / Chapter 3.5.13. --- Gel Electrophoresis of RNA Integrity --- p.65 / Chapter 3.5.14. --- cDNA Expression Array --- p.65 / Chapter 3.5.15. --- Cell Staining Using Cytospin --- p.66 / Chapter 3.5.16. --- Annexin V-FITC/Propidium Iodide Apoptosis Detection --- p.66 / Chapter 3.5.17. --- Weighing the Spleen and Tumor --- p.67 / Chapter 3.5.18. --- Preparing Samples for the Eosinophilic Cationic Protein Fluoroenzymeimmunoassay --- p.67 / Chapter 3.5.19. --- Statistical Analysis --- p.67 / Chapter Part III - --- Results: Pre-functional Assays / Chapter Chapter 4: --- "Extraction, Endotoxin Measurement, In vitro Cytotoxicity Testing, and the Selection of Optimal Concentration" / Chapter 4.1. --- Extraction efficiency --- p.68 / Chapter 4.1.1. --- Introduction --- p.68 / Chapter 4.1.2. --- Results --- p.68 / Chapter 4.2. --- Endotoxin Level --- p.69 / Chapter 4.2.1. --- Introduction --- p.69 / Chapter 4.2.2. --- Results and Interpretation --- p.69 / Chapter 4.3. --- Cytotoxicity --- p.70 / Chapter 4.3.1. --- Introduction --- p.70 / Chapter 4.3.2. --- Results and Interpretation --- p.71 / Chapter 4.3.2.1. --- Peripheral Blood Mononuclear Cells (PBMC) --- p.71 / Chapter 4.3.2.2. --- Eosinophils --- p.72 / Chapter 4.4. --- The Optimal Concentration (OC) --- p.76 / Chapter 4.4.1. --- Introduction --- p.76 / Chapter 4.4.2. --- Results and Interpretation --- p.76 / Chapter Part IV- --- Results: Immunomodulatory Activities of Cordyceps sinensis as a Single Herb / Chapter Chapter 5: --- Mitogenic Activity --- p.80 / Chapter 5.1. --- Introduction --- p.80 / Chapter 5.2. --- Results --- p.80 / Chapter 5.3. --- Discussion --- p.81 / Chapter Chapter 6: --- Cytokines and Cytokine Receptors --- p.84 / Chapter 6.1. --- Introduction --- p.84 / Chapter 6.2. --- Results --- p.84 / Chapter 6.2.1. --- Effects of Natural Cordyceps sinensis and HERBSnSENSEŚёØ Cordyceps on the Induction of Cytokines from Lymphocytes --- p.84 / Chapter 6.2.1.1. --- TNFa --- p.84 / Chapter 6.2.1.2. --- IL-6 --- p.85 / Chapter 6.2.1.3. --- IL-10 --- p.85 / Chapter 6.2.2. --- Effects of Natural Cordyceps sinensis and HERBSnSENSEŚёØ Cordyceps on the Induction of Cytokines from Monocytes --- p.92 / Chapter 6.2.2.1. --- IL-1β --- p.92 / Chapter 6.2.2.2. --- IL-6 --- p.92 / Chapter 6.2.2.3. --- IL-10 --- p.97 / Chapter 6.2.2.4. --- TNFα --- p.97 / Chapter 6.2.3. --- Effects of Natural Cordyceps sinensis and HERBSnSENSEŚёØ Cordyceps on the Expression of Cytokine Receptor --- p.102 / Chapter 6.2.4. --- Effects of Natural Cordyceps sinensis and HERBSnSENSEŚёØ Cordyceps on the Gene Expression of Cytokines and Cytokine Receptors in Peripheral Blood Mononuclear Cells --- p.105 / Chapter 6.3. --- Discussion --- p.112 / Chapter Chapter 7: --- Macrophage Functions: Phagocytosis and Release of Reactive Oxygen Species (ROS) --- p.116 / Chapter 7.1 --- Introduction --- p.116 / Chapter 7.2. --- Results --- p.117 / Chapter 7.2.1. --- Phagocytosis --- p.117 / Chapter 7.2.2. --- Release of Reactive Oxygen Species (ROS) --- p.117 / Chapter 7.3. --- Discussion --- p.124 / Chapter Chapter 8: --- Apoptosis of Selected Cancer Cell Lines --- p.126 / Chapter 8.1. --- Introduction --- p.126 / Chapter 8.2. --- Results --- p.127 / Chapter 8.2.1. --- Differential Cytotoxic Effects of natural Cordyceps sinensis and HERBSnSENSEŚёØ Cordyceps on Various Cancer Cell Lines In vitro --- p.127 / Chapter 8.2.2. --- Differential Anti-Proliferative Effects of natural Cordyceps sinensis and HERBSnSENSEŚёØ Cordyceps on Various Cancer Cell Lines In vitro --- p.129 / Chapter 8.2.3. --- Differential Apoptotic Effects of Natural Cordyceps sinensis and HERBSnSENSEŚёØ Cordyceps on Various Cancer Cell Lines In vitro --- p.131 / Chapter 8.2.3.1. --- Peripheral Blood Mononuclear Cells --- p.131 / Chapter 8.2.3.2. --- Hepatocarcinoma Hep-3B --- p.131 / Chapter 8.2.3.3. --- Human Eosinophilic Leukemic Cell Line --- p.134 / Chapter 8.2.3.4. --- Human Mast Cell Line --- p.134 / Chapter 8.2.3.5. --- Human Leukemic Cell Line (HL-60) --- p.138 / Chapter 8.2.3.6. --- Murine Macrophages/Monocytes Cell Line PU5-18 --- p.138 / Chapter 8.2.3.7. --- Murine Erhlich Ascites Tumor (EAT) --- p.142 / Chapter 8.2.3.8. --- Murine Sarcoma 180 (SC-180) --- p.142 / Chapter 8.3. --- Discussion --- p.145 / Chapter Part V- --- Results: Immunomodulatory Activities of Cordyceps sinensis in Concoction / Chapter Chapter 9: --- The In vivo Animal Model --- p.147 / Chapter 9.1. --- introduction --- p.147 / Chapter 9.2. --- Results --- p.148 / Chapter 9.2.1. --- The ICR Mice Model --- p.148 / Chapter 9.2.1.1. --- In vivo Effects of Natural C. sinensis and HERBSnSENSEŚёØ Cordyceps on the Ascitic Fluid Production of ICR Mice --- p.148 / Chapter 9.2.1.2. --- Effects of Natural C. sinensis and HERBSnSENSEŚёØ Cordyceps on the Survival of Tumor-bearing ICR Mice --- p.149 / Chapter 9.3. --- The BALB/c Mice Model --- p.153 / Chapter 9.3.1. --- In vivo Effects of HERBSnSENSEŚёØ Cordyceps on Spleen and Tumor Weight --- p.153 / Chapter 9.3.2. --- Effects of HERBSnSENSEŚёØ Cordyceps on the Mitogenic Activities of Spleen Cells --- p.154 / Chapter 9.3.3. --- "In vivo Effects of HERBSnSENSEŚёØ Cordyceps on the Cell Surface Expression of CD3, CD4, and CD8" --- p.157 / Chapter 9.3.4. --- Effects of HERBSnSENSEŚёØ Cordyceps on the Cytokine Release from Cultured Spleen Cells --- p.161 / Chapter 9.3.4.1. --- TNFα --- p.161 / Chapter 9.3.4.2. --- IFNγ --- p.163 / Chapter 9.3.4.3. --- IL-2 --- p.163 / Chapter 9.3.4.4. --- IL-4 --- p.163 / Chapter 9.3.4.5. --- IL-6 --- p.167 / Chapter 9.3.4.6. --- IL-10 --- p.167 / Chapter 9.3.4.7. --- IL-12p70 --- p.167 / Chapter 9.3.4.8. --- Monocyte Chemoattractant Protein(MCP)-1 --- p.167 / Chapter 9.3.5. --- In vivo Effects of HERBSnSENSEŚёØ Cordyceps on the Cytokine Synthesis --- p.172 / Chapter 9.4. --- Discussion --- p.174 / Chapter Chapter 10: --- In vitro Studies on Eosinophils and Peripheral Blood Mononuclear Cells --- p.178 / Chapter 10.1. --- Introduction --- p.178 / Chapter 10.2. --- Results --- p.180 / Chapter 10.2.1. --- In vitro Effects of Wheeze-Relief Formula on the Survival of IL-5 Enhanced Eosinophils --- p.180 / Chapter 10.2.2. --- In vitro Effects of Wheeze-Relief Formula on the Degranulation of Eosinophils --- p.180 / Chapter 10.2.3. --- In vitro Effects of Wheeze-Relief Formula on the Surface Expression of Adhesion Molecules and Chemokine Receptors on Eosinophils --- p.183 / Chapter 10.2.4. --- In vitro Effects of Wheeze-Relief Formula on the Surface Expression of Adhesion Molecules on Eosinophils --- p.183 / Chapter 10.2.5. --- In vitro Effects of Wheeze-Relief Formula on the Cytokine Release from Peripheral Blood Mononuclear Cells --- p.187 / Chapter 10.2.6. --- In vitro Effects of Wheeze-Relief Formula on the Gene Expression Profile of Cytokines and Cytokine Receptors of Peripheral Blood Mononuclear Cells --- p.187 / Chapter 10.3. --- Discussion --- p.196 / Chapter Chapter 11: --- The Clinical Trial: Analysis of Serological Markers --- p.200 / Chapter 11.1. --- Introduction --- p.200 / Chapter 11.2. --- Results --- p.202 / Chapter 11.2.1. --- Demographic Data and Drop-out Cases --- p.202 / Chapter 11.2.2. --- Lung Function Test --- p.202 / Chapter 11.2.3. --- Steroid Dosage --- p.202 / Chapter 11.2.4. --- Serological Markers --- p.205 / Chapter 11.3. --- Discussion --- p.215 / Chapter Part VI - --- Conclusion / Chapter Chapter 12: --- Concluding Remarks and Future Perspectives --- p.217 / Chapter Part VII- --- Appendix / Parent Information Sheet --- p.222 / 家長資訊 --- p.223 / Consent Form --- p.224 / Licence to Conduct Animal Experiments --- p.225 / Bibliography --- p.227

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 3 uppsatser.

In animals immunized with 2,4 dinitrophenyl (DNP) hapten-carrier protein conjugates, no in vitro cellular response is elicited by DNP, either alone, or when coupled to a heterologous carrier. In contrast, animals immunized with haptenic peptide-carrier conjugates do mount an in vitro cellular response towards the haptenic peptide. This apparent inconsistency led us to compare the in vivo and in vitro cellular immune responses to a synthetic peptide antigen and its DNP derivative to determine the activation specificity of the cells evoking this response. Guinea pigs were immunized with either the DNP substituted immunogen (DNP-N-10-C) or its unsubstituted form (N-10-C) and subsequent in vivo or in vitro cellular activation was evaluated for DNP alone, DNP coupled to the homologous determinant, and DNP coupled to heterologous carriers. The data suggests that in DNP-N-10-C immune guinea pigs, DNP substitution opens a new determinant exhibiting, in antigen reactive cells, a unique specificity towards the DNP moiety as well as a portion of the peptide to which it is conjugated. However the DNP group by itself does not have the configurational requirement to evoke cellular activation. It therefore plays a minor role in activation of the cellular immune response; the major contribution being supplied by the peptide portion of the 'shared' determinant. / Science, Faculty of / Microbiology and Immunology, Department of / Graduate

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Thesis (M.P.H.)--University of Michigan, 1947.