2024-03-29T01:19:30Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/124012019-08-30T11:37:00Zcom_10033_6811com_10033_6799col_10033_6877
Reichardt, Peter
Gunzer, Matthias
2007-06-20T10:45:50Z
2007-06-20T10:45:50Z
2006
Results Probl Cell Differ 2006, 43:199-218
0080-1844
17068973
http://hdl.handle.net/10033/12401
T cell activation is crucial for the development of specific immune reactions. It requires physical contact between T cells and antigen-presenting cells (APC). Since these cells are initially located at distinct positions in the body, they have to migrate and find each other within secondary lymphoid organs. After encountering each other both cells have to maintain a close membrane contact sufficiently long to ensure successful signaling. Thus, there is the necessity to temporarily synchronize the motile behavior of these cells. Initially, it had been proposed that during antigen recognition, T cells receive a stop signal and maintain a stable contact with APC for several hours when an appropriate APC has been encountered. However, direct cell observation via time-lapse microscopy in vitro and in vivo has revealed a different picture. While long contacts can be observed, many interactions appear to be very short and sequential despite efficient signaling. Thus, two concepts addressing the biophysics of T cell activation have emerged. The single encounter model proposes that after a period of dynamic searching, a T cell stops to interact with one appropriately presenting APC until signaling is completed. The serial encounter model suggests that T cells are able to collect a series of short signals by different APC until a critical activation threshold is achieved. Future research needs to clarify the relative importance of short and dynamic versus long-lived T cell-APC encounters for the outcome of T cell activation. Furthermore, a thorough understanding of the molecular events underlying the observed complex motility patterns will make these phenomena amenable for intervention, which might result in the identification of new types of immune modulating drugs.
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The biophysics of T lymphocyte activation in vitro and in vivo.
Article2018-06-12T17:20:22ZT cell activation is crucial for the development of specific immune reactions. It requires physical contact between T cells and antigen-presenting cells (APC). Since these cells are initially located at distinct positions in the body, they have to migrate and find each other within secondary lymphoid organs. After encountering each other both cells have to maintain a close membrane contact sufficiently long to ensure successful signaling. Thus, there is the necessity to temporarily synchronize the motile behavior of these cells. Initially, it had been proposed that during antigen recognition, T cells receive a stop signal and maintain a stable contact with APC for several hours when an appropriate APC has been encountered. However, direct cell observation via time-lapse microscopy in vitro and in vivo has revealed a different picture. While long contacts can be observed, many interactions appear to be very short and sequential despite efficient signaling. Thus, two concepts addressing the biophysics of T cell activation have emerged. The single encounter model proposes that after a period of dynamic searching, a T cell stops to interact with one appropriately presenting APC until signaling is completed. The serial encounter model suggests that T cells are able to collect a series of short signals by different APC until a critical activation threshold is achieved. Future research needs to clarify the relative importance of short and dynamic versus long-lived T cell-APC encounters for the outcome of T cell activation. Furthermore, a thorough understanding of the molecular events underlying the observed complex motility patterns will make these phenomena amenable for intervention, which might result in the identification of new types of immune modulating drugs.oai:repository.helmholtz-hzi.de:10033/145802019-08-30T11:35:14Zcom_10033_6811com_10033_6799col_10033_6877
Schiller, Meinhard
Metze, Dieter
Luger, Thomas A
Grabbe, Stephan
Gunzer, Matthias
2007-11-15T12:33:05Z
2007-11-15T12:33:05Z
2006-05-01
Exp. Dermatol. 2006, 15(5):331-41
0906-6705
16630072
10.1111/j.0906-6705.2006.00414.x
http://hdl.handle.net/10033/14580
The innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-kappaB activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-alpha, and production of type I IFNs (IFN-alpha and IFN-beta), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response.
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Immune response modifiers--mode of action.
Article2018-06-12T22:57:59ZThe innate immune system governs the interconnecting pathways of microbial recognition, inflammation, microbial clearance, and cell death. A family of evolutionarily conserved receptors, known as the Toll-like receptors (TLRs), is crucial in early host defense against invading pathogens. Upon TLR stimulation, nuclear factor-kappaB activation and the interferon (IFN)-regulatory factor 3 pathway initiate production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor-alpha, and production of type I IFNs (IFN-alpha and IFN-beta), respectively. The innate immunity thereby offers diverse targets for highly selective therapeutics, such as small molecular synthetic compounds that modify innate immune responses. The notion that activation of the innate immune system is a prerequisite for the induction of acquired immunity raised interest in these immune response modifiers as potential therapeutics for viral infections and various tumors. A scenario of dermal events following skin cancer treatment with imiquimod presumably comprises (i) an initial low amount of pro-inflammatory cytokine secretion by macrophages and dermal dendritic cells (DCs), thereby (ii) attracting an increasing number type I IFN-producing plasmacytoid DCs (pDCs) from the blood; (iii) Langerhans cells migrate into draining lymph nodes, leading to an increased presentation of tumor antigen in the draining lymph node, and (iv) consequently an increased generation of tumor-specific T cells and finally (v) an accumulation of tumoricidal effector cells in the treated skin area. The induction of predominately T helper (Th)1-type cytokine profiles by TLR agonists such as imiquimod might have further benefits by shifting the dominant Th2-type response in atopic diseases such as asthma and atopic dermatitis to a more potent Th1 response.oai:repository.helmholtz-hzi.de:10033/162332019-08-30T11:36:05Zcom_10033_6811com_10033_6799col_10033_6877
Niesner, Raluca
Andresen, Volker
Neumann, Jens
Spiecker, Heinrich
Gunzer, Matthias
Helmholtz Centre for Infection Research, Junior Research Group Immunodynamics, D-38124 Braunschweig, Germany.
2008-01-17T09:55:02Z
2008-01-17T09:55:02Z
2007-10-01
The power of single and multibeam two-photon microscopy for high-resolution and high-speed deep tissue and intravital imaging. 2007, 93 (7):2519-29 Biophys. J.
0006-3495
17557785
10.1529/biophysj.106.102459
http://hdl.handle.net/10033/16233
Biophysical journal
Two-photon microscopy is indispensable for deep tissue and intravital imaging. However, current technology based on single-beam point scanning has reached sensitivity and speed limits because higher performance requires higher laser power leading to sample degradation. We utilize a multifocal scanhead splitting a laser beam into a line of 64 foci, allowing sample illumination in real time at full laser power. This technology requires charge-coupled device field detection in contrast to conventional detection by photomultipliers. A comparison of the optical performance of both setups shows functional equivalence in every measurable parameter down to penetration depths of 200 microm, where most actual experiments are executed. The advantage of photomultiplier detection materializes at imaging depths >300 microm because of their better signal/noise ratio, whereas only charge-coupled devices allow real-time detection of rapid processes (here blood flow). We also find that the point-spread function of both devices strongly depends on tissue constitution and penetration depth. However, employment of a depth-corrected point-spread function allows three-dimensional deconvolution of deep-tissue data up to an image quality resembling surface detection.
en
Animals
Brain
Calibration
Cell Nucleus
Equipment Design
Hippocampus
Image Processing, Computer-Assisted
Lasers
Light
Mice
Mice, Transgenic
Microscopy
Microscopy, Confocal
Photons
Sepharose
The power of single and multibeam two-photon microscopy for high-resolution and high-speed deep tissue and intravital imaging.
Article2018-06-12T17:59:55ZTwo-photon microscopy is indispensable for deep tissue and intravital imaging. However, current technology based on single-beam point scanning has reached sensitivity and speed limits because higher performance requires higher laser power leading to sample degradation. We utilize a multifocal scanhead splitting a laser beam into a line of 64 foci, allowing sample illumination in real time at full laser power. This technology requires charge-coupled device field detection in contrast to conventional detection by photomultipliers. A comparison of the optical performance of both setups shows functional equivalence in every measurable parameter down to penetration depths of 200 microm, where most actual experiments are executed. The advantage of photomultiplier detection materializes at imaging depths >300 microm because of their better signal/noise ratio, whereas only charge-coupled devices allow real-time detection of rapid processes (here blood flow). We also find that the point-spread function of both devices strongly depends on tissue constitution and penetration depth. However, employment of a depth-corrected point-spread function allows three-dimensional deconvolution of deep-tissue data up to an image quality resembling surface detection.oai:repository.helmholtz-hzi.de:10033/191962019-08-30T11:36:59Zcom_10033_6811com_10033_6799col_10033_6877
Behnsen, Judith
Narang, Priyanka
Hasenberg, Mike
Gunzer, Frank
Bilitewski, Ursula
Klippel, Nina
Rohde, Manfred
Brock, Matthias
Brakhage, Axel A
Gunzer, Matthias
Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
2008-02-26T14:15:58Z
2008-02-26T14:15:58Z
2007-02
Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans. 2007, 3 (2):e13 PLoS Pathog.
1553-7374
17274685
10.1371/journal.ppat.0030013
http://hdl.handle.net/10033/19196
PLoS pathogens
The fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients. Normally, macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional (2-D) environment of the alveolar lumen or Candida growing in tissue microabscesses, which are composed of a three-dimensional (3-D) extracellular matrix. However, neither the cellular dynamics, the per-cell efficiency, the outcome of this interaction, nor the environmental impact on this process are known. Live imaging shows that the interaction of phagocytes with Aspergillus or Candida in 2-D liquid cultures or 3-D collagen environments is a dynamic process that includes phagocytosis, dragging, or the mere touching of fungal elements. Neutrophils and alveolar macrophages efficiently phagocytosed or dragged Aspergillus conidia in 2-D, while in 3-D their function was severely impaired. The reverse was found for phagocytosis of Candida. The phagocytosis rate was very low in 2-D, while in 3-D most neutrophils internalized multiple yeasts. In competitive assays, neutrophils primarily incorporated Aspergillus conidia in 2-D and Candida yeasts in 3-D despite frequent touching of the other pathogen. Thus, phagocytes show activity best in the environment where a pathogen is naturally encountered. This could explain why "delocalized" Aspergillus infections such as hematogeneous spread are almost uncontrollable diseases, even in immunocompetent individuals.
en
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17274685
Animals
Aspergillus fumigatus
Candida albicans
Cell Movement
Cells, Cultured
Dendritic Cells
Environment
Humans
Luminescent Proteins
Mice
Mice, Inbred BALB C
Neutrophils
Phagocytes
Phagocytosis
Promoter Regions (Genetics)
Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans.
Article2018-06-13T19:47:49ZThe fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients. Normally, macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional (2-D) environment of the alveolar lumen or Candida growing in tissue microabscesses, which are composed of a three-dimensional (3-D) extracellular matrix. However, neither the cellular dynamics, the per-cell efficiency, the outcome of this interaction, nor the environmental impact on this process are known. Live imaging shows that the interaction of phagocytes with Aspergillus or Candida in 2-D liquid cultures or 3-D collagen environments is a dynamic process that includes phagocytosis, dragging, or the mere touching of fungal elements. Neutrophils and alveolar macrophages efficiently phagocytosed or dragged Aspergillus conidia in 2-D, while in 3-D their function was severely impaired. The reverse was found for phagocytosis of Candida. The phagocytosis rate was very low in 2-D, while in 3-D most neutrophils internalized multiple yeasts. In competitive assays, neutrophils primarily incorporated Aspergillus conidia in 2-D and Candida yeasts in 3-D despite frequent touching of the other pathogen. Thus, phagocytes show activity best in the environment where a pathogen is naturally encountered. This could explain why "delocalized" Aspergillus infections such as hematogeneous spread are almost uncontrollable diseases, even in immunocompetent individuals.oai:repository.helmholtz-hzi.de:10033/382032019-08-30T11:27:39Zcom_10033_6811com_10033_6799col_10033_6877
Niesner, Raluca
Gericke, Karl-Heinz
2008-09-26T11:47:35Z
2008-09-26T11:47:35Z
2008-02-01
Frontiers of Physics in China, 3(2008)88-104
http://hdl.handle.net/10033/38203
Fluorescence lifetime imaging in biosciences: Technologies and applications
Article2018-06-13T00:26:02Z