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A Kunkl

Publications and source records attributed to A Kunkl.

43 records · Page 3Linked to original sources
PubMed1981

The role of germinal centres in the generation of immunological memory.

Germinal centres are areas of B lymphocytes proliferation that appear in primary lymphoid follicles after immunization. The results summarized here implicate these structures in the establishment of immunological memory for antibody production. It appears that after primary immunization antigen-antibody-complement complexes become trapped on the membrane of specialized dendritic cells in lymphoid follicles, and these complexes provide the stimulus for germinal centre formation. In support of this, immunization with preformed antigen-antibody complexes, rather than with antigen, leads to the earlier appearance of germinal centres and memory cells, and also accelerates the selective triggering of precursors capable of producing high affinity antibodies.

Animals↗
PubMed1981

The generation of memory cells. V. Preferential priming of IgG1 B memory cells by immunization with antigen IgG2 antibody complexes.

We have studied the effects of priming mice with complexes of dinitrophenylated (DNP)-haemocyanin (KLH) and anti-DNP antibody on the generation of DNP-specific B memory cells producing IgG1 or IgG2 antibodies. Immunization with DNP-KLH alone (with or without adjuvant) induced roughly equal proportions of IgG1 and IgG2 memory cells, at all times after priming. In sharp contrast, immunization with DNP-KLH polyclonal anti-DNP antibody complexes induced 80%--90% IgG1 memory cells, especially early after priming. Further studies using conventional and hybridoma anti-DNP antibodies showed that this effect was induced by complexes containing IgG2 antibodies, and not by those made with IgG1 antibodies. The latter induced roughly equal proportions of IgG1 and IgG2 memory cells. Priming for preferential IgG1 memory was not induced by complexes made with (Fab')2 fragments of IgG2a antibody, nor was it seen in T cell-deprived mice immunized with antigen IgG2a complexes. The mechanisms involved in this phenomenon are unknown, but presumably reflect the well established capacity of immune complexes to concentrate in lymphoid follicles, which seem to be sites of B memory-cell generation.

Animals↗
PubMed1981

The generation of memory cells. IV. Immunization with antigen-antibody complexes accelerates the development of B-memory cells, the formation of germinal centres and the maturation of antibody affinity in the secondary response.

Hapten (DNP)-specific B-memory cells were induced by priming mice with soluble or alum precipitated DNP-haemocyanin (KLH) plus Bordetella pertussis or CNP-KLH-anti-DNP antibody complexes at equivalence. Cells from mice given complexes gave a substantial adoptive IgG response five days after priming, whereas those from mice given antigen with conventional adjuvant did not give a comparable response until day 14. Soluble antigen induced poor memory, even 14 days after primary immunization. The emergence of transferable B-memory cells correlated closely with the appearance of germinal centres in lymphoid follicles of the spleen. Furthermore, the relative affinity of the adoptive secondary IgG response induced by priming with complexes was already maximal on day 6. In contrast, the response of memory cells from mice given antigen on alum, increased in affinity between 6 and 23 days after priming. These data support the concept (see Klaus, Humphrey, Kunkl & Dongworth, 1980) that trapping of antigen-antibody complexes in lymphoid follicles induces the formation of germinal centres, which in turn give rise to functional B-memory cells. They further suggest that such retained complexes play a role in selective triggering of high-affinity precursor cells.

Animals↗
PubMed1980

Selective effects of cyclosporin A on functional B cell subsets in the mouse.

Cyclosporin A, an immunosuppressive peptide of fungal origin, was believed to selectively affect T lymphocyte functions and to have minimal affects on B lymphocytes. This study shows that, in the mouse, T-dependent B cells and those responding to certain T-independent antigens (so-called TI-1 antigens) are indeed resistant to the drug. However, B cells responsive to other TI antigens (TI-2) are exquisitely sensitive. Thus, doses of the drug that completely abrogate responses to dinitrophenylated (DNP) Ficoll or dextran enhance the response to DNP-lipopolysaccharide and have minimal effects on the response to DNP-Brucella abortus. Virgin T helper cells are sensitive to the drug, whereas primed T cells are not. Cyclosporin A sensitivity therefore represents a novel marker of functional B cell subsets in the mouse and presumably points to fundamental physiologic differences between such subsets.

Animals↗
PubMedDate not supplied

Handling of retroviral antigens by human antigen-presenting cells.

Antigen-specific T helper cells play an important role in retroviral infections. Indeed, they provide help for B-cell activation and antibody production and for clonal expansion of cytolytic lymphocytes. Therefore, we used retrovirus-specific human T helper clones in order to define modes of antigen presentation, antigen-presenting cells and the molecular context of Th epitopes that could be exploited in the design of immunogens aimed at optimizing the Th cell response. In particular, we describe several mechanisms of receptor-mediated antigen uptake that enhance the stimulation of human T-cell clones specific for HIV and HTLV-1 antigens; we report on the differential recognition of Th epitopes depending on the molecular-viral context; we show that dendritic cells are the most efficient presenting cells and are essential for the induction of in vitro primary Th cell responses; and finally, we propose that Th cells specific for internal, conserved antigens of HIV such as reverse transcriptase, may be candidates for intrastructural help resulting in induction of envelope specific antibodies.

Antigen Presentation↗
PubMedDate not supplied

Response of CAPD patients with a high incidence of peritonitis to intraperitoneal immunoglobulin therapy.

This study has demonstrated that in the majority of high-peritonitis-incidence (PI) CAPD patients the defective opsonic activity levels in the peritoneal dialysis effluent (PDE) are restored for 3 weeks by a 12 g IP injection of immunoglobulins (Ig). Further studies showed that in a minority of high-PI CAPD patients who also had low PDE IgG and opsonic activity levels, IP Ig therapy did not significantly reduce the PI. To evaluate this phenomenon we utilized this therapy in 20 high-PI CAPD patients undergoing IP Ig therapy for an average of 24 months daily for 3 weeks (12 g every 3 weeks) and analyzed: 1) PDE IgG levels; 2) PDE opsonic activity; 3) peritoneal macrophage (PM0) membrane-bound IgG; 4) PDE Interleukin-1 (IL-1) levels; 5) PM0 membrane Fc receptor number. The results showed that in the 15 patients in whom Ig therapy reduced PI, there were long-lasting increases in the PDE IgG, opsonic activity and IL-1 levels, as well as a normal PM0 Fc receptor number and PM0 reversibly bound infused Ig. Conversely, the five patients in whom the IP Ig did not reduce the PI showed only transient increases in PDE IgG and opsonic activity levels, no PDE IL-1 increase, and the PM0 were deficient in Fc receptors and, therefore, unable to take up the infused Ig. We conclude that in high-PI CAPD patients there are different peritoneal immune defense abnormalities and that their identification is, therefore, important for the correct choice of therapy to improve these defects.

Adult↗