Antigen receptor signalling of B-cells in common variable immunodeficiency:
Gespeichert in:
| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 111 Bl. graph. Darst. 30 cm |
Internformat
MARC
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Datensatz im Suchindex
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| adam_text | CONTENTS
CONTENTS
SUMMARY 1
1. INTRODUCTION 3
1.1. A SHORT OVERVIEW ON THE
IMMUNE SYSTEM 3
1.2. B-CELL DEVELOPMENT AND
DIFFERENTIATION 4
1.2.1. EARLY B-CELL DEVELOPMENT 4
1.2.2. PERIPHERAL B-CELL DEVELOPMENT 5
1.2.3. THE GERMINAL
CENTER REACTION 5
1.2.4. T-CELL INDEPENDENT
IMMUNE RESPONSES 6
1.2.5. IMMUNOGLOBULIN ISOTYPES 6
1.2.6. INNATE-LIKE B1 B CELLS 7
1.3. B-CELL SUBPOPULATIONS IN THE PERIPHERAL
BLOOD 7
1.4. B-CELL RECEPTOR SIGNALLING 8
1.4.1. PROXIMAL BCR SIGNALLING, THE
PI3K/AKT AND THE
MAPK PATHWAY 9
1.4.2. CA
2+
SIGNALLING IN B CELLS 10
1.4.3. THE NF-KB PATHWAY 11
1.5. T-CELL RECEPTOR
SIGNALLING 13
1.6. THE
INFLUENCE OF INHIBITORY RECEPTORS ON BCR SIGNALLING 13
1.7. FAILURE
OF ADAPTIVE OR INNATE
IMMUNITY RESULTS IN IMMUNODEFICIENCY 15
1.7.1. COMBINED IMMUNODEFICIENCIES ....15
1.7.2. COMMON VARIABLE IMMUNODEFICIENCY 15
1.8. CHARACTERIZATION AND
OCCURRENCE OF CD21
LOW
B CELLS 16
1.9. AIMS OF THE
STUDY
R
18
2. RESULTS 20
2.1. BCR SIGNALLING IS ALTERED
IN CVID 21 LOW PATIENTS 20
2.1.1. SIGNALLING EVENTS PROXIMAL TO THE
BCR: IGA, LYN,
SYK AND BTK
ARE PRE-ACTIVATED
IN CD21
|0W
B CELLS AND CAN BE FURTHER
INCREASED BY BCR TRIGGERING 20
2.1.2. THE PI3K/AKT PATHWAY IS PRE-ACTIVATED IN CD21
LOW
B CELLS BUT NORMAL IN CD21
POS
B CELLS 22
2.1.3. PHOSPHORYLATION OF P38 IS INCREASED WITH AND WITHOUT BCR
STIMULATION IN CD21
POS
AND CD21
|0W
B CELLS 22
2.1.4. PLCY2 IS MARKEDLY PRE-PHOSPHORYLATED
IN CVID PATIENTS B CELLS AND CAN BE
READILY ACTIVATED UPON STIMULATION 22
2.1.5. UNRAVELING
THE MECHANISMS
OF DECREASED CA
2+
ENTRY IN B CELLS OF CVID 21 LOW
PATIENTS 24
2.1.6. BCR-MEDIATED ACTIVATION
OF THE CANONICAL NF-KB PATHWAY IS IMPAIRED IN B-CELL
SUBPOPULATIONS OF CVID 21 LOW PATIENTS 43
2.2. FUNCTIONAL ANALYSIS
OF B-CELLS IN CVID 21 LOW PATIENTS 45
2.3. CHARACTERIZATION OF B CELLS
IN PATIENTS WITH
ORAM
AND CARD11 DEFICIENCY 49
HTTP://D-NB.INFO/1044614013
CONTENTS
2.3.1. B CELLS IN ORAM DEFICIENCY 49
2.3.2. B-CELL PHENOTYPE AND
FUNCTION IN CARD11 DEFICIENCY 51
2.4. UNRAVELING CA
2+
MOBILIZATION IN T
CELLS AND NK CELLS OF CVID 21 LOW PATIENTS 55
3. DISCUSSION 61
3.1. BCR SIGNALLING IN CD21
LW
B
CELLS 61
3.2. THE FUNCTIONAL
CAPACITY OF CD21
|0W
B CELLS
OF CVID SMB-
21LOW PATIENTS 71
3.3. CA
2+
MOBILIZATION
IN T CELLS
AND NK CELLS
OF CVID PATIENTS 78
4. MATERIALS AND METHODS 80
4.1. PATIENTS AND
HEALTHY CONTROLS 80
4.2. CELL
BIOLOGICAL METHODS 80
4.2.1. ISOLATION OF PBMCS 80
4.2.2. CELL CULTURE AND CELL
CULTIVATION 80
4.2.3. CELL SURFACE STAINING FOR FLUORESCENCE ACTIVATED CELL SORTING
(FACS) 81
4.2.4. INTRACELLULAR STAINING OF PHOSPHORYLATED SIGNALLING
MOLECULES 81
4.2.5. MEASUREMENT OF CA
2+
MOBILISATION BY FACS 82
4.2.6. FACS-SORTING OF HUMAN
B-CELL SUBPOPULATIONS 83
4.2.7. DETERMINATION OF ACTIVATION MARKERS ON B CELLS 83
4.2.8. DETERMINATION OF IL-2
BY INTRACELLULAR FACS 84
4.2.9. UP-REGULATION OF T-CELL ACTIVATION
MARKERS 84
4.2.10.
T-CELL PROLIFERATION 84
4.2.11.
NK-CELL DEGRANULATION 85
4.2.12.
PURIFICATION OF B
CELLS BY NEGATIVE SELECTION 86
4.2.13.
IGM ELISA 87
4.2.14.
B-CELL PROLIFERATION 87
4.2.15.
NUCLEOFECTION OF DT40
CELLS 87
9
4.3. MOLECULAR BIOLOGICAL
METHODS 88
4.3.1. ISOLATION OF RNA 88
4.3.2. GENERATION OF CDNA 88
4.3.3. ISOLATION OF GENOMIC
DNA 89
4.3.4. POLYMERASE CHAIN REACTION (PCR) 89
4.3.5. AGAROSE GEL
ELECTROPHORESIS 89
4.3.6. QUANTITATIVE PCR 90
4.3.7. KREC ASSAY 91
4.3.8. AMPLIFICATION OF HUMAN SIGLECIO 92
4.3.9. RESTRICTION ENDONUCLEASE TREATMENT,
DNA DEPHOSPHORYLATION AND
LIGATION 92
4.3.10.
TRANSFORMATION OF CHEMICALLY COMPETENT
E. COLI 93
4.3.11.
DNA SEQUENCING 93
4.3.12.
STRATEGY OF SIGLECIO CLONING 94
4.4. BIOCHEMICAL METHODS 94
4.4.1. PREPARATION AND
PROCESSING OF PROTEIN EXTRACTS 94
4.4.2. SODIUM DODECYL SULFATE POLYACRYLAMIDE
GEL ELECTROPHORESIS (SDS-PAGE) 95
4.4.3. WESTERN BLOTTING 95
4.4.4. STRIPPING OF PVDF MEMBRANES 96
CONTENTS
4.5. CHEMICALS 96
4.6. STATISTICAL ANALYSIS 96
5. REFERENCES 97
6. APPENDIX. 109
6.1. ABBREVIATIONS 109
6.2. PUBLICATIONS 111
ACKNOWLEDGEMENT / DANKSAGUNG
F
|
| any_adam_object | 1 |
| author | Keller, Bärbel |
| author_GND | (DE-588)1044613939 |
| author_facet | Keller, Bärbel |
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| dewey-full | 571.967 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
| dewey-raw | 571.967 |
| dewey-search | 571.967 |
| dewey-sort | 3571.967 |
| dewey-tens | 570 - Biology |
| discipline | Biologie Medizin |
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| spelling | Keller, Bärbel Verfasser (DE-588)1044613939 aut Antigen receptor signalling of B-cells in common variable immunodeficiency vorgelegt von Bärbel Keller 2013 111 Bl. graph. Darst. 30 cm txt rdacontent n rdamedia nc rdacarrier Freiburg (Breisgau), Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027009795&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Keller, Bärbel Antigen receptor signalling of B-cells in common variable immunodeficiency |
| subject_GND | (DE-588)4113937-9 |
| title | Antigen receptor signalling of B-cells in common variable immunodeficiency |
| title_auth | Antigen receptor signalling of B-cells in common variable immunodeficiency |
| title_exact_search | Antigen receptor signalling of B-cells in common variable immunodeficiency |
| title_full | Antigen receptor signalling of B-cells in common variable immunodeficiency vorgelegt von Bärbel Keller |
| title_fullStr | Antigen receptor signalling of B-cells in common variable immunodeficiency vorgelegt von Bärbel Keller |
| title_full_unstemmed | Antigen receptor signalling of B-cells in common variable immunodeficiency vorgelegt von Bärbel Keller |
| title_short | Antigen receptor signalling of B-cells in common variable immunodeficiency |
| title_sort | antigen receptor signalling of b cells in common variable immunodeficiency |
| topic_facet | Hochschulschrift |
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