Al-Sammak F.F. The characterization of mucosal immune response in healthy volunteers vaccinated against Helicobacter Pylori-derived antigens and challenged with CagA+ Strain: Diss. (Magdeburg, 2015). - ОГЛАВЛЕНИЕ / CONTENTS

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ОбложкаAl-Sammak F.F. The characterization of mucosal immune response in healthy volunteers vaccinated against Helicobacter Pylori-derived antigens and challenged with CagA+ Strain: Diss. on zur Erlangung des akad. Grades doctor rerum naturalium genehmigt durch die Fak. fur Naturwiss. der Univ. Magdeburg / F.F.Al-Sammak. - Magdeburg: [s.n.], 2015. - 200 p, [2] p.: ill. - Bibliogr.: p. 169-200. 
 

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Оглавление / Contents
 
Acknowledgments .............................................. viii
Abstract ....................................................... ix
Zusammenfassung ................................................. x

1    Introduction ............................................... 1
1.1  HP Virulence ............................................... 1
     1.1.1  Adhesins ............................................ 2
     1.1.2  Cytotoxin-associated Gene Pathogenicity Island
            (cag PAI) ........................................... 3
     1.1.3  Duodenal Ulcer Promoting A (DupA) ................... 5
     1.1.4  High Temperature Requirement A (Htra) ............... 5
     1.1.5  Lipopolysaccharide (LPS) ............................ 6
     1.1.6  Motility ............................................ 6
     1.1.7  Urease .............................................. 7
     1.1.8  Vacuolating Cytotoxin A (VacA) ...................... 7
     1.1.9  Gamma-glutamyl Transpeptidase (GGT) ................. 8
1.2  Immune Response to HP ...................................... 8
     1.2.1  IL-8 Chemokine ..................................... 13
     1.2.2  IL-17 Family of Cytokines .......................... 13
     1.2.3  IL-12 Family of Cytokines .......................... 18
1.3  Gastritis ................................................. 27
1.4  HP Vaccine ................................................ 30
1.5  Rationale for Ph.D. Research .............................. 31

2    Materials & Methods ....................................... 34
2.1  Study Design .............................................. 34
     2.1.1  Human Cell Line Experiments ........................ 34
     2.1.2  Human Clinical Studies ............................. 38
2.2  Molecular Methods ......................................... 41
     2.2.1  Primer Design ...................................... 41
     2.2.2  Protocol ........................................... 44
     2.2.3  Normalization ...................................... 48
2.3  Protein Analytical Methods ................................ 51
     2.3.1  Immunohistochemistry (IHC) ......................... 51
     2.3.2  Immunofluorescence (IF) ............................ 51
     2.3.3  SDS-PAGE and Western Blotting (WB) ................. 52
     2.3.4  Enzyme-linked Immunosorbent Assay (ELISA) .......... 5:
2.4  Statistical Analyses ...................................... 56

3    Results ................................................... 57
3.1  Gene Expression in Human Cell Lines ....................... 57
     3.1.1  Descriptive Analysis ............................... 57
     3.1.2  Principal Component Analysis (PCA) ................. 57
3.2  Immunostaining of Gastric Mucosa .......................... 70
3.3  Western Blotting (WB) ..................................... 74
3.4  The Vaccine Study ......................................... 82
     3.4.1  Descriptive Analysis ............................... 85
     3.4.2  Univariate Analysis (Permutation Test) ............. 89
     3.4.3  Principal Component Analysis (PCA) ................ 101
     3.4.4  Cluster Analysis .................................. 107
     3.4.5  Classification .................................... 128

4    Discussion ............................................... 147
4.1  Key Molecule: pl9 ........................................ 147
     4.1.1  Novel Expression .................................. 147
     4.1.2  Predicted Modification ............................ 149
     4.1.3  Unknown Interaction ............................... 151
     4.1.4  Familiar Function ................................. 152
4.2  Characterization of Mucosal Immune Response .............. 154
     4.2.1  P Class Immunity .................................. 154
     4.2.2  Q Class State ..................................... 159
     4.2.3  R Class Response .................................. 160
     4.2.4  Inferred Implications ............................. 161
4.3  Translational Medicine ................................... 163
     4.3.1  HP Gastritis Revisited ............................ 163
     4.3.2  Preventive Diagnostic Tool ........................ 164
4.4  Limitations and Future Work .............................. 167

Bibliography .................................................. 169


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