Cytodynamics and ontogeny of the immune reponse of Xenopus laevis against sheep erythrocytes

Development ◽  
1973 ◽  
Vol 29 (1) ◽  
pp. 73-85
Author(s):  
Gerald M. Kidder ◽  
Laurens N. Ruben ◽  
Jean M. Stevens
Keyword(s):  
Xenopus Laevis ◽  
Cell Response ◽  
Single Injection ◽  
Quantitative Measure ◽  
Peak Level ◽  
Primary Response ◽  
Secondary Response ◽  
Red Cell ◽  
Sheep Erythrocytes ◽  
Morphological Criteria

The heterologous red cell response of Xenopus laevis larvae and post-metamorphic toadlets was investigated by means of the immuno-cytoadherence (ICA) technique. Sheep erythrocytes (SRBC) were employed as immunogen. Toadlets responded to a single injection of immunogen within 4 days, and exhibited a peak level of rosette-forming cells (RFC) in their spleens at 8 days post-injection. Toadlets immunized against sheep erythrocytes gave only a very slight response when tested against rat erythrocytes. A secondary response, much greater in magnitude than the primary response, was evident within 2days when previously immunized toadlets were reinjected with the same immunogen. It was concluded that the ICA technique provides a quantitative measure of an acute immune response in these animals. Larvae which had passed through stage 50 of Nieuwkoop & Faber exhibited substantial increases in RFC in the spleens when tested 6–10 days after injection with sheep erythrocytes. Significantly increased frequencies of RFC in thymi were also noted in these larvae, but the numbers involved were very low and varied considerably. Histological observations of these larvae revealed lymphoid maturation of the spleens and thymi to be essentially complete. Larvae which had not reached stage 50 according to external morphological criteria, but whose lymphoid organs had matured to a degree equivalent to stage 50, also exhibited strong anti-SRBC response in the spleens. Response in the thymi was low and not statistically significant. Larvae injected at a stage when lymphocytic differentiation was complete in the thymi but had not begun in the spleens did not exhibit an elevated splenic RFC frequency when tested after the spleens had matured. These data suggest that the heterologous red cell response in the larval spleen is dependent upon antigenic challenge to spleens which have reached the stage 50 equivalent in their histogenesis.

scholarly journals IMMUNOLOGICAL MEMORY IN VITRO

1971 ◽  
Vol 133 (4) ◽  
pp. 846-856 ◽  
Author(s):  
Gordon N. Radcliffe ◽  
Michael A. Axelrad
Keyword(s):  
Spleen Cell ◽  
Primary Response ◽  
Secondary Response ◽  
Spleen Cells ◽  
Sheep Erythrocytes ◽  
Early Primary ◽  
Primary Type ◽  
Type Response

The immune responses to sheep erythrocytes of mouse spleen cell suspensions from immune and nonimmune donors were compared in vitro. In vivo immunity was only transiently reflected in vitro, and 8 wk after in vivo immunization the responses of cultures from immunized and nonimmunized mice were virtually identical. There appeared to be two mechanisms for an antibody response to sheep erythrocytes. The first was responsible for the early primary response and is unmodified in the immune animal though contributing little to subsequent in vivo responses due to its suppressibility by specific antibody. The second was expressed in the in vivo secondary response but not on in vitro challenge of spleen cells from mice immunized many weeks previously; spleen cell cultures from such immune mice, freed from the antibody of the in vivo environment, once again demonstrate a pure primary-type response.

scholarly journals SUPPRESSION OF MEMORY BY PASSIVE IMMUNIZATION LATE IN THE PRIMARY RESPONSE

1971 ◽  
Vol 133 (4) ◽  
pp. 857-863 ◽  
Author(s):  
Michael A. Axelrad
Keyword(s):  
Cell Response ◽  
Passive Immunization ◽  
Immunological Memory ◽  
Primary Response ◽  
Sheep Erythrocytes ◽  
Full Peak

The acquisition of a capacity to respond well to sheep erythrocytes in the presence of anti-SRBC antibody was taken as an indication of the presence of immunological memory. By the use of passive immunization, both the primary IgG plaque-forming cell response and the establishment of memory were abolished, despite occurrence of a full peak IgM PFC response. Evidence for regarding the aquisition of memory and the IgM PFC and IgG PFC responses as three separate processes was presented. Antibody on day 3 of the response to 1.5 x 108 SRBC abolished formation of memory; this effect was less if passive immunization was further delayed and absent by day 10.

scholarly journals Brief Report: Immune Response in Mice with Plasma-Cell Tumor (X5563) Assayed by Agar Plaque Technique

Blood ◽  
1968 ◽  
Vol 31 (2) ◽  
pp. 252-257 ◽  
Author(s):  
SHINJI HIRANO ◽  
YUKIO IMAMURA ◽  
FUMIMARO TAKAKU ◽  
KIKU NAKAO
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Plasma Cell ◽  
Cellular Level ◽  
Primary Response ◽  
Cell Tumor ◽  
Secondary Response ◽  
Sheep Erythrocytes ◽  
Plasma Cell Tumor

Abstract The immune response to sheep erythrocytes in mice with the gamma-type plasma-cell tumor (X5563) was measured on a cellular level by agar plaque technique of Jerne et al. It was demonstrated that there was a reduction in the number of plaque-forming cells involved in the primary response but not in the secondary response in the mice which were immunized shortly before the inoculation of the tumor. These findings indicate that the lowered antibody response in mice with the tumor is due to a diminished number of antibody-forming cells.

scholarly journals POS0461 RESPONSE TO BIOLOGIC THERAPY IN RHEUMATOID ARTHRITIS: RETHINKING OUR CLASSIFICATION

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 462.1-462
Author(s):  
E. Vallejo-Yagüe ◽  
S. Kandhasamy ◽  
E. Keystone ◽  
A. Finckh ◽  
R. Micheroli ◽  
...  
Keyword(s):  
Treatment Response ◽  
Real World ◽  
Observational Studies ◽  
Initial Response ◽  
Primary Response ◽  
Sustained Response ◽  
Secondary Response ◽  
Real World Data ◽  
World Data ◽  
Secondary Failure

Background:In rheumatoid arthritis (RA), primary failure with biologic treatment may be understood as lack of initial clinical response, while secondary failure would be loss of effectiveness after an initial response. Despite these clinical concepts, there is no unifying operational definition of primary and secondary non-response to RA treatment in observational studies using real-world data. On top of data-driven challenges, when conceptualizing secondary non-responders, it is unclear if the mechanism behind loss of effectiveness after a brief initial response is similar to loss of effectiveness after previous benefit sustained over time.Objectives:This viewpoint aims to motivate discussion on how to define primary and secondary non-response in observational studies. Ultimately, we aim to trigger expert committees to develop standard terminology for these concepts.Methods:We discuss different methodologies for defining primary and secondary non-response in observational studies. To do so, we shortly overview challenges characteristic of performing observational studies in real-world data, and subsequently, we conceptualize whether treatment response should be a dichotomous classification (Primary response/non-response; Secondary response/non-response), or whether one should consider three response categories (Primary response/non-response; Primary sustained/non-sustained response; Secondary response/non-response).Results:RA or biologic registries are a common data source for studying treatment response in real-world data. While registries include disease-specific variables to assess disease progression, missing data, loss of follow-up, and visits restricted to the year or mid-year visit may present a challenge. We believe there is a general agreement to assess primary response within the first 6 month of treatment. However, conceptualizing secondary non-response, one could wonder if a patient with brief initial response and immediate loss of it should belong to the same response category as a patient who relapses after a period of prior benefit that was sustained over time. Until this concern is clarified, we recommend considering a period of sustained response as a pre-requisite for secondary failure. This would result in the following three categories: a) Primary non-response: Lack of response within the first 6 months of treatment; b) Primary sustained response: Maintenance of a positive effectiveness outcome for at least the first 12 months since treatment start; c) Secondary non-response: Loss of effectiveness after achieved primary sustained response. Figure 1 illustrates this classification through a decision tree. Since the underlying mechanisms for treatment failure may differ among the above-mentioned categories, we recommend to use the three-category classification. However, since this may pose additional methodological challenges in real-world data, optionally, a dichotomous 12-month time-point may be used to assess secondary non-response (unfavourable outcome after 12-months) in comparison to primary non-response or non-sustained response (unfavourable outcome within the first 12-months). Similarly, to study primary response, the solely 6-month timepoint may be used.Conclusion:A unified operational definition of treatment response will minimize heterogeneity among observational studies and help improve the ability to draw cross-study comparisons, which we believe would be of particular interest when identifying predictors of treatment failure. Thus, we hope to open the room for discussion and encourage expert committees to work towards a common approach to assess treatment primary and secondary non-response in RA in observational studies.Disclosure of Interests:Enriqueta Vallejo-Yagüe: None declared, Sreemanjari Kandhasamy: None declared, Edward Keystone Speakers bureau: Amgen, AbbVie, F. Hoffmann-La Roche Inc., Janssen Inc., Merck, Novartis, Pfizer Pharmaceuticals, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb Company, Celltrion, Myriad Autoimmune, F. Hoffmann-La Roche Inc, Gilead, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis, Grant/research support from: Amgen, Merck, Pfizer Pharmaceuticals, PuraPharm, Axel Finckh Speakers bureau: Pfizer, Eli-Lilly, Paid instructor for: Pfizer, Eli-Lilly, Consultant of: AbbVie, AB2Bio, BMS, Gilead, Pfizer, Viatris, Grant/research support from: Pfizer, BMS, Novartis, Raphael Micheroli Consultant of: Gilead, Eli-Lilly, Pfizer and Abbvie, Andrea Michelle Burden: None declared

Cognate CD4 help is essential for the reactivation and expansion of CD8 memory T cells directed against the hematopoietic cell–specific dominant minor histocompatibility antigen, H60

Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4273-4280 ◽  
Author(s):  
Su Jeong Ryu ◽  
Kyung Min Jung ◽  
Hyun Seung Yoo ◽  
Tae Woo Kim ◽  
Sol Kim ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Primary Response ◽  
Hematopoietic Cell ◽  
Secondary Response ◽  
Memory Cd8 T Cells ◽  
Specific Memory ◽  
Cd4 Help ◽  
Different Response

AbstractIn contrast to previous notions of the help-independency of memory CD8 T cells during secondary expansion, here we show that CD4 help is indispensable for the re-expansion of once-helped memory CD8 T cells, using a hematopoietic cell–specific dominant minor histocompatibility (H) antigen, H60, as a model antigen. H60-specific memory CD8 T cells generated during a helped primary response vigorously expanded only when rechallenged under helped conditions. The help requirement for an optimal secondary response was confirmed by a reduction in peak size by CD4 depletion, and was reproduced after skin transplantation. Helpless conditions or noncognate separate help during the secondary response resulted in a significant reduction in the peak size and different response kinetics. Providing CD4 help again during a tertiary challenge restored robust memory expansion; however, the repeated deprivation of help further reduced clonal expansion. Adoptively transferred memory CD8 T cells did not proliferate in CD40L−/− hosts. In the CD40−/− hosts, marginal memory expansion was detected after priming with male H60 cells but was completely abolished by priming with peptide-loaded CD40−/− cells, suggesting the essential role of CD40 and CD40L in memory responses. These results provide insight into the control of minor H antigen-specific CD8 T-cell responses, to maximize the graft-versus-leukemia response.

Differential expression of Broad-Complex transcription factors may forecast tissue-specific developmental fates during Drosophila metamorphosis

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3275-3287 ◽  
Author(s):  
I.F. Emery ◽  
V. Bedian ◽  
G.M. Guild
Keyword(s):  
Western Blot ◽  
Expression Patterns ◽  
Primary Response ◽  
Protein Isoforms ◽  
Secondary Response ◽  
C Protein ◽  
Tissue Specific ◽  
Specific Outcome ◽  
C Proteins ◽  
Broad Complex

The steroid hormone ecdysone initiates metamorphosis in Drosophila melanogaster by activating a cascade of gene activity that includes primary response transcriptional regulators and secondary response structural genes. The Broad-Complex (BR-C) primary response gene is composed of several distinct genetic functions and encodes a family of related transcription factor isoforms. Our objective was to determine whether BR-C isoforms were components of the primary ecdysone response in all tissues and whether tissue-specific isoform expression is associated with tissue-specific metamorphic outcomes. We used specific antibody reagents that recognize and distinguish among the Z1, Z2 and Z3 BR-C protein isoforms to study protein expression patterns during the initial stages of metamorphosis. Western blot analyses demonstrated that BR-C isoforms are induced at the onset of metamorphosis, each with unique kinetics of induction and repression. Whole-mount immunostaining showed that the BR-C proteins accumulate in the nuclei of all larval and imaginal tissues indicating that the BR-C is induced as a primary response in many tissues. Several tissues express different levels and combinations of the BR-C isoforms suggesting that the BR-C is important in determining the tissue-specific outcome of many parallel ecdysone response cascades. For example, prepupal salivary glands (destined for histolysis during metamorphosis) express Z1 isoforms while imaginal discs (destined for cell differentiation and morphogenesis) shift from the synthesis of Z2 isoforms to the synthesis of Z1 isoforms. The prepupal central nervous system (destined for tissue remodeling) expresses all isoforms, with Z3 predominating. Salivary gland chromosome immunostaining indicated that BR-C proteins interact directly with numerous loci in the polytene genome. Finally, western blot analyses showed that distinct BR-C genetic functions can be correlated with single and specific BR-C protein isoforms.

scholarly journals Modified LDL Particles Activate Inflammatory Pathways in Monocyte-derived Macrophages: Transcriptome Analysis

2018 ◽  
Vol 24 (26) ◽  
pp. 3143-3151 ◽  
Author(s):  
Alexander N. Orekhov ◽  
Yumiko Oishi ◽  
Nikita G. Nikiforov ◽  
Andrey V. Zhelankin ◽  
Larisa Dubrovsky ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Atherosclerotic Lesion ◽  
Density Lipoprotein ◽  
Primary Response ◽  
Secondary Response ◽  
Modified Ldl ◽  
Ldl Particles ◽  
Regulator Genes ◽  
Lipid Metabolism Genes

Background: A hallmark of atherosclerosis is its complex pathogenesis, which is dependent on altered cholesterol metabolism and inflammation. Both arms of pathogenesis involve myeloid cells. Monocytes migrating into the arterial walls interact with modified low-density lipoprotein (LDL) particles, accumulate cholesterol and convert into foam cells, which promote plaque formation and also contribute to inflammation by producing proinflammatory cytokines. A number of studies characterized transcriptomics of macrophages following interaction with modified LDL, and revealed alteration of the expression of genes responsible for inflammatory response and cholesterol metabolism. However, it is still unclear how these two processes are related to each other to contribute to atherosclerotic lesion formation. Methods: We attempted to identify the main mater regulator genes in macrophages treated with atherogenic modified LDL using a bioinformatics approach. Results: We found that most of the identified genes were involved in inflammation, and none of them was implicated in cholesterol metabolism. Among the key identified genes were interleukin (IL)-7, IL-7 receptor, IL- 15 and CXCL8. Conclusion: Our results indicate that activation of the inflammatory pathway is the primary response of the immune cells to modified LDL, while the lipid metabolism genes may be a secondary response triggered by inflammatory signalling.

scholarly journals THE IMMUNE RESPONSE TO SHEEP ERYTHROCYTES IN THE MOUSE

1967 ◽  
Vol 126 (1) ◽  
pp. 15-33 ◽  
Author(s):  
David Eidinger ◽  
Hugh F. Pross
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Latent Period ◽  
Lymphoid Cells ◽  
Secondary Response ◽  
Lymphoid Tissues ◽  
Antibody Activity ◽  
Cellular Activity ◽  
Sheep Erythrocytes ◽  
Draining Lymph Node

The direct and indirect plaque technique for the detection of antibody-forming cells against sheep erythrocytes was utilized for the investigation of a number of biological parameters of the primary and secondary immune response on a cellular level. The sequential pattern of 19S followed by 7S antibody formation was elicited in the primary response after a latent period of at least 1–2 days and 2–3 days respectively. The secondary response initiated 140 days after primary immunization, in contrast, was characterized by the simultaneous appearance of 19S and 7S antibody-forming cells after an observed latent period of 2–3 days. The cellular dynamics of the recruitment phase of the respective immunoglobulins in the primary and secondary response was interpreted as evidence for the derivation of the two classes of immunoglobulins from separate progenitors. The 19S antibody-forming cells were derived predominantly by a process of transformation and maturation and 7S antibody formers by a process of cellular division with a doubling time of about 12 hr. The draining lymph node exhibited maximal immunological reactivity due to its capacity to retain the particulate antigen. This capacity was considerably enhanced in the sensitized draining lymph node. Minimal cellular activity was also noted in distal lymphoid tissues which included the thymus. Focal cellular activity was observed in the draining lymph node for 60 days after immunization. Subsequently, very low level plaque-forming cellular activity was observed in association with persistence of maximal antibody activity. The appearance at 120 days of a generalized peak of cellular activity in lymphoid tissues throughout the host was considered an explanation for this discrepancy. The change in distribution of cellular antibody-forming activity, from a local to a generalized lymphatic response during the late phase of the immune response, implied a fundamental alteration in homeostatic mechanisms associated with maintenance of immune reactivity. Further manifestations of such an alteration were indicated by the appearance of 2-ME-sensitive 7S antibody nearly 3 months after primary intradermal immunization, which in the ensuing 5 months was associated with, and inversely related to, two major fluctuations in 2-ME-resistant 7S antibody. Evidence for the existence of immunological memory in the 19S system was not established in the present work. 19S anamnesis, for which evidence was derived from measurements of circulating antibody levels, was interpreted from cellular studies as the result of the substantial activity of previously uncommitted 19S lymphoid cells in distal lymphoid tissue associated with previously committed 19S cells contained in the draining lymph node.

scholarly journals EVOLUTION OF THE IMMUNE RESPONSE

1964 ◽  
Vol 119 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Ben W. Papermaster ◽  
Richard M. Condie ◽  
Joanne Finstad ◽  
Robert A. Good
Keyword(s):  
Adaptive Immunity ◽  
Primary Response ◽  
Antigenic Stimulation ◽  
Secondary Response ◽  
Immunologic Reactivity ◽  
Starch Gel ◽  
Eptatretus Stoutii ◽  
Amia Calva ◽  
Secondary Stimulation ◽  
Bacteriophage T2

1. The California hagfish, Eptatretus stoutii, seems to be completely lacking in adaptive immunity: it forms no detectable circulating antibody despite intensive stimulation with a range of antigens; it does not show reactivity to old tuberculin following sensitization with BCG; and gives no evidence of homograft immunity. 2. Studies on the sea lamprey, Petromyzon marinus, have been limited to the response to bacteriophage T2 and hemocyanin in small groups of spawning animals. They suggest that the lamprey may have a low degree of immunologic reactivity. 3. One holostean, the bowfin (Amia calva) and the guitarfish (Rhinobatos productus), an elasmobranch, showed a low level of primary response to phage and hemocyanin. The response is slow and antibody levels low. Both the bowfin and the guitarfish showed a vigorous secondary response to phage, but neither showed much enhancement of reactivity to hemocyanin in the secondary response. The bowfin formed precipitating antibody to hemocyanin, but the guitarfish did not. Both hemagglutinating and precipitating antibody to hemocyanin were also observed in the primary response of the black bass. 4. The bowfin was successfully sensitized to Ascaris antigen, and lesions of the delayed type developed after challenge at varying intervals following sensitization. 5. The horned shark (Heterodontus franciscii) regularly cleared hemocyanin from the circulation after both primary and secondary antigenic stimulation, and regularly formed hemagglutinating antibody, but not precipitating antibody, after both primary and secondary stimulation with this antigen. These animals regularly cleared bacteriophage from the circulation after both the primary and secondary stimulation with bacteriophage T2. Significant but small amounts of antibody were produced in a few animals in the primary response, and larger amounts in the responding animals after secondary antigenic stimulation. 6. Studies by starch gel and immunoelectrophoresis show that the hagfish has no bands with mobilities of mammalian gamma globulins; that the lamprey has a single, relatively faint band of this type; and that multiple gamma bands are characteristic of the holostean, elasmobranchs, and teleosts studied. By this method of study, the bowfin appeared to have substantial amounts of gamma2 globulin. 7. We conclude that adaptive immunity and its cellular and humoral correlates developed in the lowest vertebrates, and that a rising level of immunologic reactivity and an increasingly differentiated and complex immunologic mechanism are observed going up the phylogenetic scale from the hagfish, to the lamprey, to the elasmobranchs, to the holosteans, and finally the teleosts.

Differential inhibition of AE1 and AE2 anion exchangers by oxonol dyes and by novel polyaminosterol analogs of the shark antibiotic squalamine

1998 ◽  
Vol 76 (5) ◽  
pp. 799-806 ◽  
Author(s):  
Seth L Alper ◽  
Marina N Chernova ◽  
Jon Williams ◽  
Michael Zasloff ◽  
Foon-Yee Law ◽  
...  
Keyword(s):  
Xenopus Laevis ◽  
Anion Exchange ◽  
Xenopus Oocytes ◽  
Red Cells ◽  
Xenopus Laevis Oocytes ◽  
Red Cell ◽  
Cell Type ◽  
Anion Exchangers ◽  
Oxonol Dyes ◽  
Assay Conditions

Oxonol and polyaminosterol drugs were examined as inhibitors of recombinant mouse AE1 and AE2 anion exchangers expressed in Xenopus laevis oocytes and were compared as inhibitors of AE1-mediated anion flux in red cells and in HL-60 cells that express AE2. The oxonols WW-781, diBA(5)C4, and diBA(3)C4 inhibited HL-60 cell Cl-/Cl- exchange with IC50 values from 1 to 7 µM, 100-1000 times less potent than their IC50 values for red cell Cl-/anion exchange. In Xenopus oocytes, diBA(5)C4 inhibited AE1-mediated Cl- efflux several hundred times more potently than that mediated by AE2. Several novel squalamine-related polyaminosterols were also evaluated as anion exchange inhibitors. In contrast to diBA(5)C4, polyaminosterol 1361 inhibited oocyte-expressed AE2 8-fold more potently than AE1 (IC50 0.6 versus 5.2 µM). The 3-fold less potent desulfo-analog, 1360, showed similar preference for AE2. It was found that 1361 also partially inhibited Cl- efflux from red cells, whereas neither polyaminosterol inhibited Cl efflux from HL60 cells. Thus, the oxonol diBA(5)C4 is >100-fold more potent as an inhibitor of AE1 than of AE2, whereas the polyaminosterols 1360 and 1361 are 8-fold more potent as inhibitors of AE2 than of AE1. Assay conditions and cell type influenced IC50 values for both classes of compounds.Key words: band 3, oxonols, squalamine, Xenopus laevis oocytes, HL-60 cells.

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