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- Carlsson, Fredrik, et al.
(författare)
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IgE enhances specific antibody and T cell responses in mice overexpressing CD23
- 2007
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:2-3, s. 261-270
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Tidskriftsartikel (refereegranskat)abstract
- IgE administered with its specific antigen in vivo induces enhanced proliferation of specific T cells as well as enhanced production of specific antibodies. Both effects are dependent on the low-affinity receptor for IgE (CD23) and the underlying mechanism is thought to be increased antigen presentation following uptake of IgE/antigen complexes via CD23+ B cells. By contrast, CD23 negatively regulates antibody responses to antigens administered with alum, i.e. without IgE. This effect has been observed as low IgG1 and IgE responses in transgenic mice overexpressing CD23 (CD23Tg). The present study was designed to test whether IgE could enhance antibody and T-cell responses in CD23Tg animals or whether CD23's downregulatory effect precludes IgE-mediated enhancement. IgE-anti-TNP administered with OVA-TNP enhances the OVA-specific antibody responses in wild-type (wt) and CD23Tg mice equally well. Interestingly, the total magnitude of antibody responses to IgE + OVA-TNP and to uncomplexed OVA-TNP, as well as to sheep erythrocytes and keyhole limpet haemocyanine, were lower in the CD23Tg mice. IgE induced proliferation of OVA-specific CD4+ T cells to the same degree in wt and CD23Tg mice. The effect on T cells was dependent on CD23+ B cells as demonstrated in in vitro proliferation assays. In conclusion, CD23 does indeed have dual immunoregulatory effects in the same animal. The receptor mediates enhancement of antibody and T-cell responses to IgE-complexed antigen, most likely via increased presentation of complexed antigen, while it negatively regulates the total antibody response to a variety of antigens.
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| 5. |
- Fors, Fredrik, 1973-, et al.
(författare)
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Terrorattackerna i London den 7 juli 2005 : Brittiska lokala och regionala myndigheters agerande och lärdomar för det svenska krishanteringssystemet
- 2006
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Strax före klockan nio på morgonen den 7 juli 2005 inträffade de första självmordsbombningarnanågonsin i Västeuropa. Tre tunnelbanetåg i centrala Londonsprängdes i en samtidig attack klockan 08.50. Ungefär en timme senare skeddeden fjärde attacken, då en bomb detonerade på en buss. Sammanlagt dödades56 människor i terrorattentatet och 755 människor skadades.Denna observatörsrapport syftar till att identifiera erfarenheter och lärdomarfrån hanteringen av terrorattentatet i London som är relevanta för det svenskakrishanteringssystemet. Detta görs genom att kartlägga händelseförloppet samtbeskriva och förklara de regionala och lokala myndigheternas agerande,beslutsfattande, samverkande och lärande i samband med terrorattentatet.I ett inledande kapitel sammanfattas lärdomar för det svenska krishanteringssystemet.Två frågor står i fokus: Vad kan svenska krishanterare lära av händelsernaden 7 juli 2005? Vilka av erfarenheterna från London är väsentligaatt ta med i den fortsatta utvecklingen av det svenska krishanteringssystemet?Andra delar av rapporten ger bakgrundsinformation kring krishantering iLondon och Storbritannien, redovisar händelseförloppet under terrorattacken,samt analyserar de brittiska organisationernas agerande.
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| 7. |
- Hjelm, Fredrik, et al.
(författare)
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A novel B cell-mediated transport of IgE-immune complexes to the follicle of the spleen.
- 2008
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 180:10, s. 6604-6610
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Tidskriftsartikel (refereegranskat)abstract
- Ag administered i.v. to mice along with specific IgE or IgG2a induces higher Ab- and CD4(+) T cell responses than Ag administered alone. The IgE effect is completely dependent on the low-affinity receptor for IgE, CD23, whereas the IgG2a effect depends on activating FcgammaRs. In vitro studies suggest that IgE/Ag is presented more efficiently than Ag alone to CD4(+) T cells by CD23(+) B cells and that IgG2a/Ag is presented by FcgammaR(+) dendritic cells (DCs). In this study, we investigate in vivo the early events leading to IgE- and IgG2a-mediated enhancement of immune responses. OVA administered i.v. in PBS in combination with specific IgE binds circulating B cells after 5 min and is found in B cell follicles bound to follicular B cells (CD23(high)) after 30 min. This novel B cell-dependent route of entry is specific for IgE because IgG2a-Ag complexes were trapped in the marginal zone. OVA-specific CD4(+) T cells were found at the T-B border in the T cell zones 12 h after immunization both with IgE/OVA or IgG2a/OVA and proliferated vigorously after 3 days. The findings suggest that IgE- and IgG2a-immune complexes are efficient stimulators of early CD4(+) T cell responses and that Ag bound to IgE has a specific route for transportation into follicles.
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| 8. |
- Hjelm, Fredrik, 1978-
(författare)
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Early Immunostimulatory Effects of IgE- and IgG Antibodies
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibodies have the ability to influence their own production in a process called antibody feedback regulation. Depending on the type of antigen and the subclass of the antibody, the outcome of feedback regulation can be complete suppression or several hundred-fold enhancement of the antibody response.IgE and IgG3 enhance responses to soluble protein antigens. Previous results suggest that IgG3-mediated enhancement of antibody responses is dependent on complement and not Fc receptors for IgG. However, the Fc receptor-deficient animals used did not completely lack the IgG3-binding FcγRI. We re-examined the role of this receptor in a new mouse strain completely lacking FcγRI and found that IgG3-mediated enhancement was unperturbed, thus confirming a role for complement. To investigate the early responses resulting in IgE-mediated enhancement of antibody responses we used biotinylated antigen and found that mature follicular B cells and to a lesser extent transitional type 2 B cells capture IgE/antigen complexes. Adoptive transfer of CD4+ T cells expressing a transgenic TCR specific for ovalbumin demonstrated that these T cells localize near the B-cell follicle after 6-12 hours and that IgE, in contrast to IgG3, significantly increased specific T cell proliferation. After 3 days the T cells had gone through several rounds of divisions and showed an activated phenotype. Additional cell transfer studies identified CD23+ B cells as the responsible effector cells. These results indicate that the mechanism underlying IgE-mediated enhancement is rapid transport of IgE/antigen complexes by follicular B cells into B-cell follicles, followed by antigen presentation by CD23+ B cells to naïve CD4+ T cells. IgG3, inducing poor T cell responses, is more likely to depend on lowering the threshold for B-cell activation by co-ligating the B-cell receptor with the complement receptor 2/CD19 complex on the surface of the B cell.
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