T-wimp mice: immune responses under limiting conditions ; implications for human "leaky" SCID
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| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | 113 S. Ill., graph. Darst. 30 cm |
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| 245 | 1 | 0 | |a T-wimp mice |b immune responses under limiting conditions ; implications for human "leaky" SCID |c vorgelegt von Kristina Hillen, geb. Brückner |
| 264 | 1 | |c 2013 | |
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Datensatz im Suchindex
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|---|---|
| adam_text | CONTENTS
CONTENTS 4
ABSTRACT 7
ABBREVIATIONS 8
1 INTRODUCTION 10
1.1 THE IMMUNE SYSTEM 10
1.2 T CELL DEVELOPMENT 11
1.2.1 T CELL DEVELOPMENT IN THE THYMUS - AN OVERVIEW 11
1.2.2 DIVERSITY OF THE *P TCR 13
1.3 T CELL SUBSETS 14
1.3.1 CD4
+
HELPER T CELLS 14
1.3.2 CYTOTOXIC CD8
+
T CELLS 15
1.3.3 PERIPHERAL YTI
+
T CELLS 18
1.4 T CELL HOMEOSTASIS 20
1.4.1 LYMPHOPENIA-INDUCED HOMEOSTATIC PROLIFERATION (LIP) 20
1.5 ANTIVIRAL IMMUNITY 22
1.5.1 ANTIGEN-SPECIFIC IMMUNE RESPONSE DURING A RESOLVED INFECTION 22
1.5.2 ANTIGEN-SPECIFIC IMMUNE RESPONSE DURING A PERSISTENT INFECTION - T
CELL EXHAUSTION 23
1.5.3 LCMV AS AN INFECTION MODEL 24
1.6 FAILURE OF HOST DEFENSE MECHANISMS IN HUMANS 25
1.6.1 SEVERE T CELL IMMUNODEFICIENCIES 25
1.6.2 PARTIAL T CELL IMMUNODEFICIENCIES 26
1.7 THE T-WIMP MOUSE MODEL 27
1.7.1 GENERATION AND IDENTIFICATION OF THE T-WIMP MUTATION 27
1.8 SLP-76 AND ITS ROLE IN THE TCR
SIGNALING PATHWAY 28
1.9 AIMS OF THE STUDY 31
2 MATERIALS AND METHODS 32
2.1 MICE, VIRUSES AND MATERIALS 32
2.1.1 MICE 32
2.1.2 NARCOTICS 33
2.1.3 VIRUSES 33
2.1.4 CELLS 33
2.1.5 CELL CULTURE MEDIA 33
2.1.6 SYNTHETIC PEPTIDE 34
2.1.7 ANTIBODIES 34
2.1.8 PRIMER 36
2.1.9 KITS 38
2.1.10 CHEMICALS, BUFFERS AND SOLUTIONS 39
4
HTTP://D-NB.INFO/1037222172
CONTENTS
2.1.11 MATERIALS FOR WESTERN BLOT ANALYSES 43
T
2.1.12 PLASTIC MATERIALS 43
2.1.13 INSTRUMENTS 44
2.2 METHODS 45
2.2.1 MOUSE GENOTYPING 45
2.2.2 TREATMENT OF MICE 47
2.2.3 PREPARATION OF MICE 48
2.2.4 DETERMINATION OF VIRAL TITERS 49
2.2.5 CYTOTOXICITY ASSAY 49
2.2.6 FLOW CYTOMETRY 50
2.2.7 MAGNETIC ACTIVATED CELL SEPARATION (MACS) 51
2.2.8 PROLIFERATION ASSAY 52
2.2.9 DETERMINATION OF ANTIBODY CONCENTRATIONS IN THE BLOOD SERUM 53
2.2.10 IMMUNOHISTOCHEMICAL DETERMINATION OF ANAS 53
2.2.11 SPECTRATYPE ANALYSES 54
2.2.12 WESTERN BLOT ANALYSES 55
2.2.13 STATISTICAL ANALYSES 56
3 RESULTS 57
3.1 THE HYPOMORPHIC SLP-76
MUTATION IN T-WIMP MICE LEADS TO IMPAIRED TCR
SIGNALING AND CAUSES PARTIAL T CELL IMMUNODEFICIENCY 57
3.1.1 A|J T CELL DEVELOPMENT IS PARTIALLY BLOCKED AT THE P-SELECTION
CHECKPOINT 57
3.1.2 T-WIMP MICE SHOW A PARTIAL T CELL LYMPHOPENIA WITH A DIFFERENT
IMPACT ON AP VERSUS YS AND
CD4
+
VERSUS CD8
+
T CELLS 59
3.1.3 REDUCTION OF NAIVE T CELLS IN T-WIMP MICE 60
3.1.4 SKEWED VP-REPERTOIRE AMONG CD4
+
BUT NOT CD8
+
T CELLS 61
3.1.5 IMPAIRED TCR-DEPENDENT T CELL ACTIVATION IN T-WIMP MICE 62
3.1.6 T HELPER CELL PHENOTYPE OF PERIPHERAL CD4
+
T CELLS IN T-WIMP MICE 63
3.2 HOW
EFFICIENT IS ANTIVIRAL IMMUNITY IN T-WIMP MICE?
65
3.2.1 T-WIMP MICE CONTROL LCMV-ARM INFECTION, BUT FAIL TO CONTROL
LCMV-WE INFECTION 65
3.2.2 IMPAIRED T CELL PROLIFERATION IN RESPONSE TO VIRAL INFECTION 66
3.2.3 PERSISTENCE OF ANTIVIRAL MEMORY CD8
+
T CELLS IS DEPENDENT ON VIRUS CONTROL 68
3.2.4 EXPRESSION OF INHIBITORY RECEPTORS ON CD8
+
T CELLS IS DIFFERENTIALLY REGULATED IN T-WIMP MICE 70
3.2.5 PARTIAL IMPAIRMENT OF IFN-Y PRODUCTION BY T-WIMP T CELLS UNDER
CONDITIONS OF VIRUS CONTROL... 72
3.2.6 T-WIMP T CELLS SHOW NORMAL ANTIGEN-SPECIFIC CYTOTOXICITY UNDER
CONDITIONS OF VIRUS CONTROL.. 74
3.2.7 T CELL-SPECIFIC IMMUNIZATION OF T-WIMP MICE FAILS TO IMPROVE VIRUS
CONTROL 75
3.3 HOMEOSTATIC PROLIFERATION OF T-WIMP T CELLS IS COMPARABLE TO
CONTROLS ....77
3.4 ANALYSES OF THE
R
T CELL PREDOMINANCE IN T-WIMP MICE 78
3.4.1 Y8 T CELL DEVELOPMENT IN T-WIMP MICE IS LESS IMPAIRED THAN AP T
CELL DEVELOPMENT 78
3.4.2 T-WIMP MICE SHOW INCREASED SINGLE POSITIVE AND FURTHER
DIFFERENTIATED Y8 T CELLS IN THE
PERIPHERY 81
5
CONTENTS
3.4.3 TCR-DEPENDENT ACTIVATION OF Y5 T CELLS IS IMPAIRED IN T-WIMP MICE
82
3.4.4 YS T CELLS PARTLY CONTROL THE IMMUNE DYSREGULATION IN T-WIMP MICE
83
3.4.5 IN THE ABSENCE OF Y8 T CELLS, VIRUS-CONTROL IS MORE EFFICIENT IN
T-WIMP MICE 84
4 DISCUSSION 85
4.1 TCR
SIGNALING REQUIREMENTS DIFFER FOR VARIOUS T CELL POPULATIONS 85
4.2 LYMPHOPENIC T-WIMP MICE DEVELOP SIGNS OF IMMUNE DYSREGULATION 89
4.3 EXPANSION OF THE ANTIVIRAL T CELL POOL, NOT T CELL EFFECTOR FUNCTION
IS
LIMITING FOR VIRUS CONTROL IN MICE WITH A HYPORESPONSIVE TCR 91
4.4
R
T CELLS IN T-WIMP MICE HAVE IMPORTANT BIOLOGICAL FUNCTION IN ANTIVIRAL
IMMUNITY AND IMMUNE REGULATION 95
4.5 CONCLUDING REMARKS 96
5 REFERENCES 98
PRESENTATIONS
AND PUBLICATIONS 112
ACKNOWLEDGEMENT/ DANKSAGUNG 113
6
|
| any_adam_object | 1 |
| author | Hillen, Kristina |
| author_GND | (DE-588)1035419610 |
| author_facet | Hillen, Kristina |
| author_role | aut |
| author_sort | Hillen, Kristina |
| author_variant | k h kh |
| building | Verbundindex |
| bvnumber | BV041583540 |
| ctrlnum | (OCoLC)861224000 (DE-599)DNB1037222172 |
| dewey-full | 571.9646 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 571 - Physiology & related subjects |
| dewey-raw | 571.9646 |
| dewey-search | 571.9646 |
| dewey-sort | 3571.9646 |
| dewey-tens | 570 - Biology |
| discipline | Biologie Medizin |
| format | Thesis Book |
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| spelling | Hillen, Kristina Verfasser (DE-588)1035419610 aut T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID vorgelegt von Kristina Hillen, geb. Brückner 2013 113 S. Ill., 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=027028753&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Hillen, Kristina T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID |
| subject_GND | (DE-588)4113937-9 |
| title | T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID |
| title_auth | T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID |
| title_exact_search | T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID |
| title_full | T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID vorgelegt von Kristina Hillen, geb. Brückner |
| title_fullStr | T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID vorgelegt von Kristina Hillen, geb. Brückner |
| title_full_unstemmed | T-wimp mice immune responses under limiting conditions ; implications for human "leaky" SCID vorgelegt von Kristina Hillen, geb. Brückner |
| title_short | T-wimp mice |
| title_sort | t wimp mice immune responses under limiting conditions implications for human leaky scid |
| title_sub | immune responses under limiting conditions ; implications for human "leaky" SCID |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027028753&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
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