scholarly journals COMPETITION OF 19S AND 7S ANTIGEN RECEPTORS IN THE REGULATION OF THE PRIMARY IMMUNE RESPONSE

1968 ◽  
Vol 128 (1) ◽  
pp. 133-152 ◽  
Author(s):  
Claudia Henry ◽  
Niels K. Jerne

Prior to sheep red cells (SRC) mice were given 7S or 19S anti-SRC antibodies or mixtures of both. All 7S preparations suppressed the immune response. All 19S preparations enhanced the primary response, as measured by an up to 15-fold increase in the number of PFC per spleen. Results obtained with mixtures showed that 7S and 19S antibodies are competitive in their effect. The kinetics of the appearance of PFC in the mouse spleen after injection of SRC suggest that the depressive effect of 7S antibody simulates a reduction in SRC dose, whereas the enhancing effect of 19S antibody appears as a temporary increase in the rate at which PFC appear. Antibodies from one animal species are quite effective in another species.

Parasitology ◽  
1971 ◽  
Vol 62 (3) ◽  
pp. 457-465 ◽  
Author(s):  
D. Conwil Jenkins ◽  
R. F. Phillipson

The kinetics of low-level repeated infections of Nippostrongylus brasiliensis in the laboratory rat were studied.The administration of five infective larvae each weekday to the rats produced an infection which was cumulative over 16 weeks and which did not produce an acute host immune response.The repeated administration of 50 larvae/weekday produced a primary immune response after 14 days. This caused partial worm expulsion and the suppression of egg output but the resistance of these rats to reinfection was not as pronounced as that seen in classical laboratory infections where heavier but less frequent larval exposures are used. The secondary worms that established in these rats did not elicit an acute host immune response even when the worm burden was as high as 756 worms.It is suggested that the kinetics of this type of infection more closely approximate those found under natural conditions than do those of a ‘classical’ laboratory infection.We wish to thank Misses G. Merchant, L. Cleaver and J. Cobb for able technical assistance, and Dr B. M. Ogilvie (National Institute for Medical Research, Mill Hill, London) for her helpful comments and discussions.


1998 ◽  
Vol 187 (6) ◽  
pp. 885-895 ◽  
Author(s):  
Yoshimasa Takahashi ◽  
Pinaki R. Dutta ◽  
Douglas M. Cerasoli ◽  
Garnett Kelsoe

To examine the role of germinal centers (GCs) in the generation and selection of high affinity antibody-forming cells (AFCs), we have analyzed the average affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific AFCs and serum antibodies both during and after the GC phase of the immune response. In addition, the genetics of NP-binding AFCs were followed to monitor the generation and selection of high affinity AFCs at the clonal level. NP-binding AFCs gradually accumulate in bone marrow (BM) after immunization and BM becomes the predominant locale of specific AFCs in the late primary response. Although the average affinity of NP-specific BM AFCs rapidly increased while GCs were present (GC phase), the affinity of both BM AFCs and serum antibodies continued to increase even after GCs waned (post-GC phase). Affinity maturation in the post-GC phase was also reflected in a shift in the distribution of somatic mutations as well as in the CDR3 sequences of BM AFC antibody heavy chain genes. Disruption of GCs by injection of antibody specific for CD154 (CD40 ligand) decreased the average affinity of subsequent BM AFCs, suggesting that GCs generate the precursors of high affinity BM AFCs; inhibition of CD154-dependent cellular interactions after the GC reaction was complete had no effect on high affinity BM AFCs. Interestingly, limited affinity maturation in the BM AFC compartment still occurs during the late primary response even after treatment with anti-CD154 antibody. Thus, GCs are necessary for the generation of high affinity AFC precursors but are not the only sites for the affinity-driven clonal selection responsible for the maturation of humoral immune responses.


1975 ◽  
Author(s):  
J. L. Brash ◽  
I. A. Feuerstein

Adhesion of platelets to glass, collagen-coated glass, albumin-coated glass, polystyrene, sulfonated polystyrene and a segmented polyurethane, has been studied in vitro. The apparatus is of the Couette flow type and allows close control of fluid shear and diffusional factors. Suspensions of washed pig platelets constitute the basic platelet medium. This can be modified by adding back red cells and specific plasma proteins in varying concentration and the platelet concentration can be varied without compromising viability. Adhesion is measured by radiolabelling methods.In the absence of red cells, low levels of adhesion were seen on all surfaces with saturation occurring at 4 to 6 platelets/1000 μ2 in 2 to 4 minutes. In the presence of red cells adhesion was much greater. Collagen was the most reactive surface and adhesion data was consistent with a platelet diffusivity 10 to 100 times that predicted by Brownian motion. The diffusivity was dependent on shear rate and hematocrit. All other surfaces showed a 2-fold increase in adhesion compared to the values without red cells. However adhesion was independent of hematocrit above 10% and reached a constant value of about 12 (less for albumin monolayer) in 2 to 10 minutes.


1993 ◽  
Vol 177 (5) ◽  
pp. 1487-1492 ◽  
Author(s):  
H R MacDonald ◽  
J L Casanova ◽  
J L Maryanski ◽  
J C Cerottini

Previous T cell receptor (TCR) sequence analysis of a panel of 23 H-2Kd restricted cytotoxic T lymphocyte (CTL) clones recognizing the decapeptide HLA-CW3 170-179 revealed a striking conservation of TCR structure, in that all clones examined used V beta 10 and J alpha pHDS58 segments. We show here that the primary response in vivo after intraperitoneal injection of DBA/2 mice with HLA-CW3 expressing transfectants of syngeneic P815 (H-2d) tumor cells is characterized by a dramatic expansion of CD8+ V beta 10+ CTL in the peritoneal cavity and draining (mesenteric) lymph node, as well as in peripheral blood. Additional analysis of TCR on HLA-CW3 immune populations by flow cytometry and polymerase chain reaction further indicates that the vast majority of responding CD8+ cells express restricted V alpha domains, a dominant J alpha segment (pHDS58), and a conserved CDR3 length for both alpha and beta chains. This novel system provides a unique opportunity to directly monitor an oligoclonal primary antigen specific immune response in vivo at the single cell level independently of functional assays.


2020 ◽  
Author(s):  
Alexandra J. Spencer ◽  
Adrian L. Smith ◽  
Barbara Fazekas de St Groth

AbstractPrevious studies suggest that recruitment of naïve T cells into a program of cell division and differentiation is a highly synchronous process under tight regulation. However it is not known whether antigen availability is the major regulator of this process, or whether other factors such as ongoing responses to unrelated antigens can affect the size of the primary response. We have developed an adoptive transfer system to investigate the efficiency with which additional antigen specific cells are recruited into an ongoing primary immune response. Recruitment of additional cells is an inverse function of the size of the response and is progressively inhibited with time. Cells recruited late into the response proliferate less, and fewer secrete IL-2 and IFN-γ. Thus the size of the response changes very little as a result of late recruitment. The inhibition of recruitment, proliferation and differentiation affects only cells of the same specificity as the ongoing response, indicating that the size of an antigen specific response is independent of any shared factors such as access to APCs, costimulation or cytokines. Thus, during infection, the immune system retains the ability to respond as necessary to secondary infections or antigens not presented until later stages of the response.


1969 ◽  
Vol 129 (2) ◽  
pp. 393-410 ◽  
Author(s):  
W. D. Armstrong ◽  
E. Diener ◽  
G. R. Shellam

The numbers of antigen-reactive cells (ARC) responding to a purified protein, the polymer of S. adelaide flagellin, have been assayed in cell populations derived from several lymphoid tissues of mice. The assay, which employs the cell transfer into lethally irradiated mice, indicates that there is a response of ARC in bone marrow in the absence of thymus cells. This suggests that the immune response to this protein antigen is not thymus dependent. The presence of relatively large numbers of ARC in Peyer's patches argues for their direct participation in the immune response in the adult mouse. The kinetics of ARC and antibody-forming cells in the early primary response employing the transfer system is described. The numbers of ARC declined during the first 2 days of the immune response, but by day 6 had increased to about five times the number in unprimed spleen cells. The rise is believed to be a result of the primary injection of antigen and therefore may be described as memory; however, these experiments have not been able to further elucidate any specific qualities of the "memory cell." Tolerance induction in C57BL/Brad mice produced by repeated injections of a cyanogen bromide digest of the antigen is described. The ARC or its precursor is shown to be the site of the lesion of tolerance by direct investigation.


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