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- Xu, Hui, 1988-
(författare)
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Modulation of B cell access to antigen by passively administered antibodies : an explanation for antibody feedback regulation?
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibody responses can be up- or down-regulated by passive administration of specific antibody together with antigen. Depending on the structure of the antigen and the antibody isotype, responses can be completely suppressed or enhanced up to a 1000-fold of what is seen in animals immunized with antigen alone.IgG suppresses primary antibody responses against erythrocytes. Suppression works well in mice lacking Fc-receptors for IgG, C1q, C3, or complement receptor 1 and 2 (CR1/2). Here, we demonstrate that IgG anti-NP given to mice together with NP-conjugated sheep erythrocytes, suppresses the generation of NP-specific extra-follicular antibody-secreting cells, NP-specific germinal center B cells, induction of memory and long-lived plasma cells. IgG increases antigen clearance but this does not explain the suppressed antibody response. It is demonstrated that IgG-mediated suppression of IgG responses is epitope specific, suggesting that epitope masking is the dominant explanation for IgG-mediated suppression of antibody responses.Both IgE and IgG3 can enhance antibody responses against soluble antigens. IgE-antigen complexes bind to recirculating B cells expressing CD23, an Fc-receptor for IgE. Thirty minutes after intravenous administration, IgE-antigen is found in splenic follicles. Subsequently, germinal center responses, antigen-specific T cell proliferation, and antibody responses are enhanced. We show that also antigen conjugated to anti-CD23 can bind to CD23+ B cells and be transported to splenic follicles. CD11+ spleen cells, rather than CD23+ B cells, present IgE-antigen complexes to T cells. Here, it is demonstrated that CD8α− conventional dendritic cells is the CD11c+ cell population presenting IgE-antigen to T cells.IgG3-mediated enhancement is dependent on CR1/2. We find that IgG3-antigen complexes, administered intravenously to mice, bind to marginal zone B cells via CR1/2. These cells then transport IgG3-antigen into splenic follicles and deposit antigen onto follicular dendritic cells. Mice treated with FTY720, a drug which dislocates marginal zone B cells from the marginal zone, impairs this transport. Studies in bone marrow chimeric mice show that CR1/2 on both B cells and follicular dendritic cells are crucial for IgG3-mediated enhancement.In summary, these observations suggest that antibodies can feedback regulate antibody responses by modulating the access of antigen to the immune system.
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| 2. |
- Xu, Zhi-Hui, 1963-
(författare)
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Mechanical Characterisation of Coatings and Composites-Depth-Sensing Indentation and Finite Element Modelling
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the past two decades depth-sensing indentation has becomea widely used technique to measure the mechanical properties ofmaterials. This technique is particularly suitable for thecharacterisation of materials at sub-micro or nano scale thoughthere is a tendency to extend its application to the micro ormacro scale. The load-penetration depth curve of depth-sensingindentation is a characteristic of a material and can be usedfor analysing various mechanical properties in addition tohardness. This thesis deals with the mechanicalcharacterisation of bulk materials, thin films and coatings,gradient materials, and composites using depth-sensingindentation. Finite element method has been resorted to as atool to understand the indentation behaviour of materials. The piling-up or sinking-in behaviour of materials plays animportant role in the accurate determination of materialsproperties using depth-sensing indentation. Finite elementsimulations show that the piling-up or sinking-in behaviour isdetermined by the material parameters, namelyE/σyratio and strain hardening exponent orexperimental parameterhe/hmaxratio, and the contact friction. Anempirical model has been proposed to relate the contact area ofindentation to theE/σyratio and thehe/hmaxratio and used to predict thepiling-up orsinking-in of materials. The existence of friction is found toenhance the sinking-in tendency of materials. A generalrelationship between the hardness and the indentationrepresentative stress valid for both soft and hard materialshas been obtained. A possible method to estimate the plasticproperties of bulk materials has been suggested. Measuring the coating-only properties requires theindentation to be done within a critical penetration depthbeyond which substrate effect comes in. The ratio of thecritical penetration depth to the coating thickness determinedby nanoindentation is independent of coating thickness andabout 0.2 for gold / nickel, 0.4 for aluminium / BK7 glass, and0.2 for diamond-like-carbon / M2 steel and alumina / nickel.Finite element simulations show that this ratio is dependent onthe combination of the coating and the substrate and moresensitive to differences in the elastic properties than in theplastic properties of the coating/substrate system. Thedeformation behaviour of coatings, such as, piling-up of thesoft coatings and cracking of the hard coatings, has also beeninvestigated using atomic force microscope. The constraint factors, 2.24 for WC phase and 2.7 for WC-Cocemented carbides, are determined through nanoindentation andfinite element simulations. A modified hardness model of WC-Cocemented carbides has been proposed, which gives a betterestimation than the Lee and Gurland hardness model. Finiteelement method has also been used to investigate theindentation behaviour of WC-Co gradient coatings. Keywords:depth-sensing indentation, nanoindentation,finite element method, atomic force microscope, mechanicalproperties, hardness, deformation, dislocations, cracks,piling-up, sinking-in, indentation size effect, thin coatings,composite, gradient materials, WC-Co, diamond-like-carbon,alumina, gold, aluminium, nickel, BK7 glass, M2 steel.
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