TY  - THES
A1  - Song, Bong-Seok
T1  - Morphodynamiken der Interaktion zwischen T-Zelle und dendritischer Zelle in dreidimensionaler extrazellulärer Matrix
T1  - Physical morphodynamics of T cell-DC-interaction in 3D extracellular matrix
N2  - Die Aktivierung der T Zelle bedarf der spezifischen Interaktion zwischen T Zelle und Antigen-präsentierender Zelle unter Ausbildung einer engen Anlagerung beider Zellmembranen („immunologische Synapse“) für Rezeptoren-Interaktionen und konsekutive Signaltransduktion. In dreidimensionaler Kollagenmatrix zeigte sich ein stereotypes, dynamisches Muster bei der Interaktion zwischen CD45RO-positiven humanen T Zellen und antigenpräsentierenden dendritischen Zellen. i) Die Kontaktaufnahme wurde stets über das Leading edge der T Zelle initiiert. ii) Beim dynamischen Kontakt wanderte die T Zelle polarisiert, mit vielen Richtungsänderungen und mit reduzierter Geschwindigkeit auf der DC-Oberfläche, nur unterbrochen von kurzen Stopp- und Abrundungsphasen. Der Uropod der T Zelle stand während der dynamischen Kontakts in kontinuierlicher Verbindung zur DC. iii) Die Loslösung der T Zelle von der DC war ein aktiver Prozess, der durch Interaktion der Vorderfront der T Zelle zu benachbarten Kollagenfasern eingeleitet wurde, gefolgt von der Lösung des Zellkörpers und des Uropods. Alternativ wurden Kontakte durch Uropod-mediierte Retention der T Zelle auf der DC-Oberfläche verlängert. Zur dynamischen molekularen Charakterisierung der Kontaktfläche wurde eine Methode zur Darstellung von Lipid-Rafts an lebenden Zellen in der 3D ECM mit BTRITC etabliert. Die Ergebnisse zeigen ein neues 3-Schritt-Konzept dynamischer und produktiver Interaktionen zwischen T Zelle und DC in vitro. Die assymetrische Kontaktzone impliziert distinkte Funktionen von Vorderfront und Uropod der T Zelle und definiert eine neuartige dynamische Kontaktform für die Signalübertragung zwischen beweglichen Zellen.
N2  - Activation of T cells is initiated through specific interaction between a T cell and an antigen-presenting cell. It is believed to be facilitated through formation of an interaction plane at the contact site, called the "immunological synapse" (IS).The IS is defined by recruitment and segregation of cell-surface receptors and adaptor proteins at the cell–cell junction, and is responsible for sustained transmission of intracellular signals. In three-dimensional collagen matrices interaction between CD45RO positive human T cells and autologous antigen-presenting dendritic cells (DC) showed a stereotypical, dynamic pattern. i) First contact was initiated through the leading edge of the migrating T cell. ii) The T cell continued to migrate across the surface of the APC during the dynamic contact with the DC, only interrupted by short static episodes or even rounding. T cell morphology during the migration on the DC was polarized, with a sticky tail called uropod being in continuous contact to the DC surface. The leading edge on the contrary continuously interacted with both the DC-surface and the surrounding interphase, iii) eventually resulting in active traction of the T cell front and body away from the DC. The uropod either detached from the DC surface as well or retained the T cell in contact to the DC, thereby prolonging the interaction. In order to characterize the dynamic molecular pattern of the contact plane a new method for visualization of lipid rafts with BTRITC within living cells in 3D extracellular matrix was established. In summary, a new 3-step-concept of dynamic and productive interactions between T cells and dendritic cells in vitro can be shown. The assymetric interaction plane between the polarized T cell and the DC implies discrete functions of leading edge and uropod of the T cell. A new form of dynamic interaction for signaling between mobile cells has been defined morphologically.
KW  - Immunologie
KW  - Morphodynamik
KW  - T Zell-Aktivierung
KW  - Dendritische Zelle
KW  - Lipid Rafts
KW  - T cell activation
KW  - immunology
KW  - morphodynamics
KW  - dendritic cell
KW  - lipid rafts
Y1  - 2005
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-15397
ER  - 
TY  - JOUR
A1  - Recke, Andreas
A1  - Konitzer, Sarah
A1  - Lemcke, Susanne
A1  - Freitag, Miriam
A1  - Sommer, Nele Maxi
A1  - Abdelhady, Mohammad
A1  - Amoli, Mahsa M.
A1  - Benoit, Sandrine
A1  - El-Chennawy, Farha
A1  - Eldarouti, Mohammad
A1  - Eming, Rüdiger
A1  - Gläser, Regine
A1  - Günther, Claudia
A1  - Hadaschik, Eva
A1  - Homey, Bernhard
A1  - Lieb, Wolfgang
A1  - Peitsch, Wiebke K.
A1  - Pföhler, Claudia
A1  - Robati, Reza M.
A1  - Saeedi, Marjan
A1  - Sárdy, Miklós
A1  - Sticherling, Michael
A1  - Uzun, Soner
A1  - Worm, Margitta
A1  - Zillikens, Detlef
A1  - Ibrahim, Saleh
A1  - Vidarsson, Gestur
A1  - Schmidt, Enno
T1  - The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts
JF  - frontiers in Immunology
N2  - IgG3 is the IgG subclass with the strongest effector functions among all four IgG subclasses and the highest degree of allelic variability among all constant immunoglobulin genes. Due to its genetic position, IgG3 is often the first isotype an antibody switches to before IgG1 or IgG4. Compared with the other IgG subclasses, it has a reduced half-life which is probably connected to a decreased affinity to the neonatal Fc receptor (FcRn). However, a few allelic variants harbor an amino acid replacement of His435 to Arg that reverts the half-life of the resulting IgG3 to the same level as the other IgG subclasses. Because of its functional impact, we hypothesized that the p.Arg435His variation could be associated with susceptibility to autoantibody-mediated diseases like pemphigus vulgaris (PV) and bullous pemphigoid (BP). Using a set of samples from German, Turkish, Egyptian, and Iranian patients and controls, we were able to demonstrate a genetic association of the p.Arg435His variation with PV risk, but not with BP risk. Our results suggest a hitherto unknown role for the function of IgG3 in the pathogenesis of PV.
KW  - immunology
KW  - dermatology
KW  - autoantibodies
KW  - allotype
KW  - pemphigus
KW  - Diagnose
KW  - pemphigoid
KW  - half-life
KW  - functional genetics
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225073
VL  - 9
ER  - 
TY  - JOUR
A1  - Schön, Michael P.
A1  - Berking, Carola
A1  - Biedermann, Tilo
A1  - Buhl, Timo
A1  - Erpenbeck, Luise
A1  - Eyerich, Kilian
A1  - Eyerich, Stefanie
A1  - Ghoreschi, Kamran
A1  - Goebeler, Matthias
A1  - Ludwig, Ralf J.
A1  - Schäkel, Knut
A1  - Schilling, Bastian
A1  - Schlapbach, Christoph
A1  - Stary, Georg
A1  - von Stebut, Esther
A1  - Steinbrink, Kerstin
T1  - COVID‐19 and immunological regulations – from basic and translational aspects to clinical implications
JF  - JDDG: Journal der Deutschen Dermatologischen Gesellschaft
N2  - The COVID‐19 pandemic caused by SARS‐CoV‐2 has far‐reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS‐CoV‐2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors.
Against this background we summarize here the current state of knowledge on the interaction of SARS‐CoV‐2/COVID‐19 with mediators of the acute phase of inflammation (TNF, IL‐1, IL‐6), type 1 and type 17 immune responses (IL‐12, IL‐23, IL‐17, IL‐36), type 2 immune reactions (IL‐4, IL‐13, IL‐5, IL‐31, IgE), B‐cell immunity, checkpoint regulators (PD‐1, PD‐L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non‐specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte‐mediated innate immune mechanisms.
From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS‐CoV‐2/COVID‐19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID‐19 pandemic; some even appear to alleviate COVID‐19.
KW  - COVID-19
KW  - SARS-CoV-2
KW  - immunology
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218205
VL  - 18
IS  - 8
SP  - 795
EP  - 807
ER  -