Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Berlin
Mensch und Buch Verl.
2014 [erschienen] 2015
|
| Schlagworte: | |
| Online-Zugang: | kostenfrei Inhaltsverzeichnis |
| Beschreibung: | Nebentitel: Die Rolle von Monozyten und Makrophagen in der Ausprägung der Empfänglichkeit für Infektionen mit lymphatischer Filariose |
| Beschreibung: | IX, 83 S. graph. Darst. |
| ISBN: | 9783863875848 |
Internformat
MARC
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| 245 | 1 | 0 | |a Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis |c vorgelegt von Noëlle Louise O'Regan |
| 246 | 1 | 3 | |a Die Rolle von Monozyten und Makrophagen in der Ausprägung der Empfänglichkeit für Infektionen mit lymphatischer Filariose |
| 264 | 1 | |a Berlin |b Mensch und Buch Verl. |c 2014 [erschienen] 2015 | |
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| 500 | |a Nebentitel: Die Rolle von Monozyten und Makrophagen in der Ausprägung der Empfänglichkeit für Infektionen mit lymphatischer Filariose | ||
| 502 | |a Berlin, Freie Univ., Diss., 2015 | ||
| 650 | 7 | |a antibodies |2 cabt | |
| 650 | 7 | |a lymphatic filariasis |2 cabt | |
| 650 | 7 | |a macrophages |2 cabt | |
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| 650 | 7 | |a monocytes |2 cabt | |
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Datensatz im Suchindex
| _version_ | 1804174723954769920 |
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| adam_text | TABLE OF CONTENTS
ABSTRACT V
LIST OF FIGURES VI
LIST OF TABLES VII
LIST OF ABBREVIATIONS VIII
1. INTRODUCTION 1
1.1. LYMPHATIC FILARIASIS 1
1.2. THE IMMUNE RESPONSE IN FILARIAL INFECTION 3
1.2
.1.
THE SPECTRUM OF CLINICAL OUTCOMES IN FILARIAL INFECTION 3
1.2.2. HOST PROTECTION IN HELMINTH INFECTION 4
1.2.2.1. EVIDENCE OF IMMUNITY IN HUMANS 5
1.2.2.2. EVIDENCE OF IMMUNITY FROM ANIMAL MODELS 5
1.2.3. HELMINTH-DERIVED IMMUNE REGULATION OF THE HOST RESPONSE 6
1.2.3.1. HOST CELLS TARGETED BY HELMINTHS TO INDUCE REGULATION 8
1.2.3.2. HELMINTH-DERIVED IMMUNOMODULATORY MOLECULES 9
1.2.3.3. FILARIAL CYSTATIN 12
1.3. BIOLOGICAL FUNCTIONS OF MONOCYTES & MACROPHAGES 13
1.3.1. MONOCYTES 13
1.3.2. MACROPHAGES 13
1.3.2.1. THE MURINE SYSTEM 13
1.3.2.2. THE HUMAN SYSTEM 14
1.3.3. THE ROLE OF MONOCYTES & MACROPHAGES IN FILARIAL INFECTION 15
1.4. ANTIBODY GLYCOSYLATION IN LYMPHATIC FILARIASIS 16
1.4.1. ANTIBODY STRUCTURE 16
1.4.2. THE ROLE OF ANTIBODIES IN LYMPHATIC FILARIASIS 16
1.4.3. FC RECEPTOR-MEDIATED ACTIVATION OF INNATE IMMUNE CELLS 17
1.4.4. GLYCOSYLATION 17
1.4.5. ANTIBODY GLYCOSYLATION 18
1.4.6. THE ROLE OF IGG GLYCOSYLATION IN DISEASE 19
2. AIMS OF THE STUDY 20
2.1. OPEN QUESTIONS & THE CONTRIBUTION OF THIS THESIS 20
2.2. HYPOTHESIS 20
2.3. AIMS AND OBJECTIVES 20
3.
M
ATERIALS 21
3.1. BIOLOGICAL RESOURCES 21
3.2. LABORATORY EQUIPMENT 21
I
HTTP://D-NB.INFO/1070960306
3.3. CONSUMABLES 21
3.4. BUFFERS AND MEDIA 22
3.4.1. BRUGIA MALAYI PURIFICATION AND CULTURE 22
3.4.2. CELL CULTURE AND PREPARATION 22
3.4.3. CELL SORTING AND FLOW CYTOMETRY 22
3.4.4. ELISA 22
3.4.5. ANTIBODY GLYCAN ANALYSIS 23
3.5. CHEMICALS AND BIOLOGICAL REAGENTS 23
3.5.1. CHEMICALS 23
3.5.2. MICROBEADS AND ANTIBODIES 23
3.5.3. CYTOKINES 24
3.5.4. OTHER REAGENTS 24
3.6. COMMERCIAL KITS 24
3.7. PRIMER SEQUENCES 25
3.8. SOFTWARE 25
4. METHODS 26
4.1. CHARACTERISATION OF THE PHENOTYPE AND FUNCTION OF MONOCYTES AND
MACROPHAGES FROM FILARIA NON-ENDEMIC NORMAL DONORS 26
4.1.1. ETHICAL STATEMENT 26
4.1.2. BRUGIA MALAYI ADULT MALE, FEMALE AND MF LYSATE AND ES PREPARATION
26
4.1.3. ISOLATION OF PBMCS FROM BUFFY COATS 26
4.1.4. ISOLATION OF CD14
+
MONOCYTES FROM PBMCS AND SUBSEQUENT DIFFERENTIATION TO
MACROPHAGES 26
4.1.5. IN VITRO STIMULATION OF MONOCYTES AND MACROPHAGES 27
4.1.6. CYTOKINE ANALYSIS 27
4.1.7. RNA EXTRACTION AND REAL-TIME PCR 27
4.1.8. HARVESTING OF ADHERED MONOCYTES AND MACROPHAGES FROM CULTURE
PLATES .... 28
4.1.9. FLOW CYTOMETRY ANALYSIS OF MONOCYTES AND MACROPHAGES 28
4.1.10. LPS STIMULATION OF MF LYSATE-DIFFERENTIATED MACROPHAGES 28
4.1.11. PHAGOCYTOSIS ASSAY 28
4.1.12. ISOLATION OF CD4
+
T CELLS FROM PBMCS AND CFSE LABELLING 29
4.1.13. MONOCYTE:CD4
+
T CELL COCULTURE 29
4.2. CHARACTERISATION OF THE WUCHERERIA BANCROFTL-EXPOSED COHORT AND
DETERMINATION OF THE PHENOTYPE AND FUNCTION OF ISOLATED MONOCYTES 30
4.2.1. ETHICAL STATEMENT 30
4.2.2. STUDY POPULATION 30
4.2.3. MEASUREMENT OF POLYCLONAL ANTIBODY ISOTYPES IN PLASMA 30
4.2.4. MEASUREMENT OF B. MALAYI LYSATE-SPECIFIC ANTIBODY ISOTYPES IN
PLASMA 31
II
4.2.5. MEASUREMENT OF FILARIAL CYSTATIN-SPECIFIC ANTIBODY ISOTYPES IN
PLASMA 31
4.2.6. ISOLATION OF PBMCS FROM WHOLE BLOOD AND SUBSEQUENT PURIFICATION
OF CD14
+
MONOCYTES 31
4.2.7. RNA EXTRACTION AND REAL-TIME PCR 32
4.2.8. IN VITRO STIMULATION OF MONOCYTES FROM W. BANCROFTI ENDEMIC
DONORS 32
4.2.9. CYTOKINE MEASUREMENT IN THE CULTURE SUPERNATANT 32
4.3. ANALYSIS OF IGG FC N-LINKED GLYCOSYLATION IN W. BANCROFTI-EXPOSED
DONORS. 33
4.3.1. STUDY POPULATION 33
4.3.2. MEASUREMENT OF POLYCONAL AND FILARIAL-SPECIFIC ANTIBODY ISOTYPES
33
4.3.3. PURIFICATION OF TOTAL IGG FROM PLASMA 33
4.3.4. IGG PEPSIN DIGESTION AND GENERATION OF FC GLYCOPEPTIDES 33
4.3.5. ENZYMATIC A/-GLYCAN RELEASE 34
4.3.6. ISOLATION AND PURIFICATION OF RELEASED N-GLYCANS 34
4.3.7. APTS LABELLING OF GLYCANS 34
4.3.8. CE-LIF N-GLYCAN PROFILING 34
4.4. STATISTICAL ANALYSES 34
5. RESULTS 35
5.1. CHARACTERISATION OF THE PHENOTYPE AND FUNCTION OF MONOCYTES AND IN
VITRO
GENERATED MACROPHAGES FROM FILARIA NON-ENDEMIC NORMAL DONORS 35
5.1.1. MONOCYTES AND MACROPHAGES RESPOND APPROPRIATELY TO IN VITRO
STIMULATION
WITH KNOWN POLARISING AGENTS 35
5.1.2. B. MALAYI FEMALE AND MF LYSATE ACT ON MONOCYTES AND MACROPHAGES
IN A
DOSE-DEPENDENT MANNER 37
5.1.3. MONOCYTES AND MACROPHAGES STIMULATED IN VITRO WITH MF LYSATE
DEVELOP A
DISTINCT ACTIVATION PHENOTYPE 38
5.1.4. 8. MALAYI FEMALE AND MF LYSATE-STIMULATED MACROPHAGES DISPLAY
IMPAIRED
PHAGOCYTOSIS 41
5.1.5. B. MALAYI MF LYSATE INTERFERES WITH MACROPHAGE DIFFERENTIATION IN
VITRO 41
5.1.6. B. MALAYI MF LYSATE-STIMULATED MONOCYTES IMPAIR CD4
+
T CELL PROLIFERATION AND
CYTOKINE PRODUCTION 42
5.1.7. NEUTRALISATION OF IL-10 OR PD-1 RESTORES CD4* T CELL IFN-Y
PRODUCTION 44
5.1.8. STIMULATION OF MONOCYTES AND MACROPHAGES WITH THE FILARIAL
IMMUNOMODULATOR
BM-CPI-2 REFLECTS THE ACTIVATION PHENOTYPE INDUCED BY B. MALAYI MF
LYSATE 45
5.2. CHARACTERISATION OF IMMUNOLOGICAL BLOOD PLASMA PARAMETERS AND THE
PHENOTYPE AND FUNCTION OF MONOCYTES FROM W. BANCROFTI-EXPOSED DONORS 47
5.2.1. FILARIAL-SPECIFIC ANTIBODY MEASUREMENTS CONFIRM THE DIAGNOSIS AND
CLASSIFICATION OF THE W. BANCROFTI-EXPOSED COHORT 47
5.2.1. MONOCYTES FROM W. BANCROFTI AS PATIENTS HAVE A REGULATORY
PHENOTYPE 48
5.2.2. MONOCYTES FROM FILARIA-EXPOSED PERSONS RESPOND EQUALLY TO 8.
MA/AYJ-SPECIFIC
STIMULI REGARDLESS OF THE IMMUNOLOGICAL BACKGROUND OF THE HOST 48
5.3. ANALYSIS OF TOTAL IGG FC W-LLNKED GLYCOSYLATION IN W.
BANCROFTI-EXPOSED
DONORS 50
5.3.1. W. BANCROFTI AS PATIENTS DISPLAY A DISTINCT ANTIBODY
GLYCOSYLATION PROFILE 50
6. DISCUSSION 53
6.1. IN VITRO STIMULATION OF HUMAN MONOCYTES AND MACROPHAGES 53
6.1.1. HUMAN MONOCYTES AND MACROPHAGES DEVELOP TYPICAL CLASSICALLY OR
ALTERNATIVELY ACTIVATED CHARACTERISTICS UNDER APPROPRIATE STIMULATION
CONDITIONS 53
6.1.2. B. MALAYI FEMALE AND MF LYSATE INDUCE DIVERSE RESPONSES IN
MONOCYTES AND
MACROPHAGES, CHARACTERISED BY DIFFERENTIAL EXPRESSION OF M1, M2 AND
REGULATORY
MARKERS 54
6.1.3. B. MALAYI FEMALE AND MF LYSATE INHIBIT PHAGOCYTOSIS 55
6.1.4. B. MALAYI MF LYSATE INTERFERES WITH MACROPHAGE DIFFERENTIATION IN
VITRO 56
6.1.5. B. MALAYI MF LYSATE-MODULATED MONOCYTES CURTAIL CD4
+
T CELL EFFECTOR
FUNCTIONS THROUGH IL-10- AND PD-1-DEPENDENT MECHANISMS 56
6.1.6. STIMULATION OF MONOCYTES AND MACROPHAGES WITH B. MALAYI CYSTATIN
(BM-CPI-
2) REFLECTS THE ACTIVATION PHENOTYPE INDUCED BY B. MALAYI MF LYSATE 57
6.2. CHARACTERISATION OF THE ANTIBODY RESPONSE AND THE PHENOTYPE AND
FUNCTION
OF MONOCYTES FROM W. BANCROFTI-EX POSED DONORS 58
6.2.1. LGG4 DOMINATES THE FILARIAL-SPECIFIC AND CYSTATIN-SPECIFIC
ANTIBODY RESPONSE OF
W. BANCROFTI AS PATIENTS 58
6.2.2. THE PHENOTYPE OF MONOCYTES FROM W. BANCROFTI AS PATIENTS REFLECTS
THAT
OBSERVED IN MONOCYTES STIMULATED IN VITRO WITH B. MALAYI MF LYSATE 58
6.3. W. BANCROFTI AS PATIENTS DISPLAY A DISTINCT ANTIBODY GLYCOSYLATION
PROFILE
CHARACTERISED BY DECREASED LEVELS OF DISIALYLATED IGG 59
7. LIMITATIONS OF THE STUDY 60
8. OUTLOOK 61
8.1. CYSTATIN AS A FILARIAL IMMUNOMODULATOR THAT CONTRIBUTES TO THE
DEVELOPMENT
OF ASYMPTOMATIC INFECTION IN LYMPHATIC FILARLASIS 61
8.2. DETERMINATION OF THE GLYCOSYLATION PROFILE OF CYSTATIN-SPECIFIC IGG
AND ITS
SUBCLASSES, AND THE ROLE OF IGG WITH DECREASED SIALYLATION 61
ZUSAMMENFASSUNG 62
B
IBLIOGRAPHY 63
PUBLICATIONS & SCIENTIFIC CONTRIBUTIONS 81
ACKNOWLEDGEMENTS 82
SELBSTSTANDIGKEITSERKLARUNG 83
IV
|
| any_adam_object | 1 |
| author | O'Regan, Noëlle Louise |
| author_facet | O'Regan, Noëlle Louise |
| author_role | aut |
| author_sort | O'Regan, Noëlle Louise |
| author_variant | n l o nl nlo |
| building | Verbundindex |
| bvnumber | BV042570840 |
| collection | ebook |
| ctrlnum | (OCoLC)912429607 (DE-599)BVBBV042570840 |
| dewey-full | 616.9652 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 616 - Diseases |
| dewey-raw | 616.9652 |
| dewey-search | 616.9652 |
| dewey-sort | 3616.9652 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Thesis Book |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV042570840 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T07:04:56Z |
| institution | BVB |
| isbn | 9783863875848 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-028004442 |
| oclc_num | 912429607 |
| open_access_boolean | 1 |
| owner | DE-188 |
| owner_facet | DE-188 |
| physical | IX, 83 S. graph. Darst. |
| psigel | ebook |
| publishDate | 2014 |
| publishDateSearch | 2015 |
| publishDateSort | 2015 |
| publisher | Mensch und Buch Verl. |
| record_format | marc |
| spelling | O'Regan, Noëlle Louise Verfasser aut Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis vorgelegt von Noëlle Louise O'Regan Die Rolle von Monozyten und Makrophagen in der Ausprägung der Empfänglichkeit für Infektionen mit lymphatischer Filariose Berlin Mensch und Buch Verl. 2014 [erschienen] 2015 IX, 83 S. graph. Darst. txt rdacontent n rdamedia nc rdacarrier Nebentitel: Die Rolle von Monozyten und Makrophagen in der Ausprägung der Empfänglichkeit für Infektionen mit lymphatischer Filariose Berlin, Freie Univ., Diss., 2015 antibodies cabt lymphatic filariasis cabt macrophages cabt microfilariae cabt monocytes cabt glycosylation Immunsuppression (DE-588)4026641-2 gnd rswk-swf Filariose (DE-588)4154338-5 gnd rswk-swf Makrophage (DE-588)4193041-1 gnd rswk-swf Lymphsystem (DE-588)4036764-2 gnd rswk-swf Immunglobulin G (DE-588)4127637-1 gnd rswk-swf Glykosylierung (DE-588)4269099-7 gnd rswk-swf Immunreaktion (DE-588)4133841-8 gnd rswk-swf Monozyt (DE-588)4285013-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Monozyt (DE-588)4285013-7 s Makrophage (DE-588)4193041-1 s Filariose (DE-588)4154338-5 s Lymphsystem (DE-588)4036764-2 s Immunreaktion (DE-588)4133841-8 s Immunsuppression (DE-588)4026641-2 s Immunglobulin G (DE-588)4127637-1 s Glykosylierung (DE-588)4269099-7 s DE-604 Erscheint auch als Online-Ausgabe urn:nbn:de:kobv:188-fudissthesis000000099186-7 http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000099186 Resolving-System kostenfrei Volltext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028004442&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | O'Regan, Noëlle Louise Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis antibodies cabt lymphatic filariasis cabt macrophages cabt microfilariae cabt monocytes cabt glycosylation Immunsuppression (DE-588)4026641-2 gnd Filariose (DE-588)4154338-5 gnd Makrophage (DE-588)4193041-1 gnd Lymphsystem (DE-588)4036764-2 gnd Immunglobulin G (DE-588)4127637-1 gnd Glykosylierung (DE-588)4269099-7 gnd Immunreaktion (DE-588)4133841-8 gnd Monozyt (DE-588)4285013-7 gnd |
| subject_GND | (DE-588)4026641-2 (DE-588)4154338-5 (DE-588)4193041-1 (DE-588)4036764-2 (DE-588)4127637-1 (DE-588)4269099-7 (DE-588)4133841-8 (DE-588)4285013-7 (DE-588)4113937-9 |
| title | Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis |
| title_alt | Die Rolle von Monozyten und Makrophagen in der Ausprägung der Empfänglichkeit für Infektionen mit lymphatischer Filariose |
| title_auth | Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis |
| title_exact_search | Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis |
| title_full | Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis vorgelegt von Noëlle Louise O'Regan |
| title_fullStr | Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis vorgelegt von Noëlle Louise O'Regan |
| title_full_unstemmed | Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis vorgelegt von Noëlle Louise O'Regan |
| title_short | Monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis |
| title_sort | monocytes and macrophages as determinants of susceptibility to infection in lymphatic filariasis |
| topic | antibodies cabt lymphatic filariasis cabt macrophages cabt microfilariae cabt monocytes cabt glycosylation Immunsuppression (DE-588)4026641-2 gnd Filariose (DE-588)4154338-5 gnd Makrophage (DE-588)4193041-1 gnd Lymphsystem (DE-588)4036764-2 gnd Immunglobulin G (DE-588)4127637-1 gnd Glykosylierung (DE-588)4269099-7 gnd Immunreaktion (DE-588)4133841-8 gnd Monozyt (DE-588)4285013-7 gnd |
| topic_facet | antibodies lymphatic filariasis macrophages microfilariae monocytes glycosylation Immunsuppression Filariose Makrophage Lymphsystem Immunglobulin G Glykosylierung Immunreaktion Monozyt Hochschulschrift |
| url | http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000099186 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028004442&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT oregannoellelouise monocytesandmacrophagesasdeterminantsofsusceptibilitytoinfectioninlymphaticfilariasis AT oregannoellelouise dierollevonmonozytenundmakrophageninderauspragungderempfanglichkeitfurinfektionenmitlymphatischerfilariose |