Manipulation of the immune response in parasitic infections

Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 665-675
Author(s):  
J.G. Howard
Keyword(s):  
Immune Response ◽  
Inbred Mouse ◽  
Lymphocyte Subset ◽  
Mouse Strains ◽  
Parasitic Infections ◽  
Research Experience ◽  
Relevant Research ◽  
Fresh Insight ◽  
Insight Into

The following brief survey considers various manoeuvres which can be applied to manipulate the immune response to parasitic infectionsin vivo. The examples quoted largely concern malaria, babesiosis, schistosomiasis and leishmaniasis, predominantly in inbred mouse strains. Since my own relevant research experience has been restricted to leishmaniasis, this will receive undue emphasis, although it does illustrate particularly well points I wish to stress. The types of intervention described do not all provide the precision of interpretation with which they are sometimes credited. Thus, effects of immunosuppression or T-cell depletion alone can usually only implicate the specific immune response (in its broad sense) in shaping the natural history and outcome of an infection or in underlying the effect of prophylactic immunization. Nevertheless, more precise delineation of lymphocyte subset involvement can be obtained by cell replacement studies in some of these models or by exclusion of antibody. The outcomes of these approaches have been (or are) predictable in most cases. More fascinating, however, are the various instances which will be stressed where totally unpredicted and contrary observations have been made which led (or may lead) to fresh insight into the disease. These serendipitous findings illustrate at the same time the value of applying the manoeuvres, even though they imply that the logical immunologist cannot yet always outsmart the parasite by design.

scholarly journals A Combined Adjuvant TF–Al Consisting of TFPR1 and Aluminum Hydroxide Augments Strong Humoral and Cellular Immune Responses in Both C57BL/6 and BALB/c Mice

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1408
Author(s):  
Qiao Li ◽  
Zhihua Liu ◽  
Yi Liu ◽  
Chen Liang ◽  
Jiayi Shu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Inbred Mouse ◽  
Effective Vaccine ◽  
Mouse Strains ◽  
Cellular Immune Responses ◽  
Recombinant Hbsag ◽  
Cellular Immune

TFPR1 is a novel adjuvant for protein and peptide antigens, which has been demonstrated in BALB/c mice in our previous studies; however, its adjuvanticity in mice with different genetic backgrounds remains unknown, and its adjuvanticity needs to be improved to fit the requirements for various vaccines. In this study, we first compared the adjuvanticity of TFPR1 in two commonly used inbred mouse strains, BALB/c and C57BL/6 mice, in vitro and in vivo, and demonstrated that TFPR1 activated TLR2 to exert its immune activity in vivo. Next, to prove the feasibility of TFPR1 acting as a major component of combined adjuvants, we prepared a combined adjuvant, TF–Al, by formulating TFPR1 and alum at a certain ratio and compared its adjuvanticity with that of TFPR1 and alum alone using OVA and recombinant HBsAg as model antigens in both BALB/c and C57BL/6 mice. Results showed that TFPR1 acts as an effective vaccine adjuvant in both BALB/c mice and C57BL/6 mice, and further demonstrated the role of TLR2 in the adjuvanticity of TFPR1 in vivo. In addition, we obtained a novel combined adjuvant, TF–Al, based on TFPR1, which can augment antibody and cellular immune responses in mice with different genetic backgrounds, suggesting its promise for vaccine development in the future.

scholarly journals Influence of genetic background on ex vivo and in vivo cardiac function in several commonly used inbred mouse strains

2010 ◽  
Vol 42A (2) ◽  
pp. 103-113 ◽  
Author(s):  
Matthew S. Barnabei ◽  
Nathan J. Palpant ◽  
Joseph M. Metzger
Keyword(s):  
Cardiac Function ◽  
Genetic Divergence ◽  
Ex Vivo ◽  
Inbred Mouse ◽  
Critical Role ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Cardiac Decompensation

Inbred mouse strains play a critical role in biomedical research. Genetic homogeneity within inbred strains and their general amenability to genetic manipulation have made them an ideal resource for dissecting the physiological function(s) of individual genes. However, the inbreeding that makes inbred mice so useful also results in genetic divergence between them. This genetic divergence is often unaccounted for but may be a confounding factor when comparing studies that have utilized distinct inbred strains. Here, we compared the cardiac function of C57BL/6J mice to seven other commonly used inbred mouse strains: FVB/NJ, DBA/2J, C3H/HeJ, BALB/cJ, 129X1/SvJ, C57BL/10SnJ, and 129S1/SvImJ. The assays used to compare cardiac function were the ex vivo isolated Langendorff heart preparation and in vivo real-time hemodynamic analysis using conductance micromanometry. We report significant strain-dependent differences in cardiac function between C57BL/6J and other commonly used inbred strains. C57BL/6J maintained better cardiac function than most inbred strains after ex vivo ischemia, particularly compared with 129S1/SvImJ, 129X1/SvJ, and C57BL/10SnJ strains. However, during in vivo acute hypoxia 129X1/SvJ and 129S1/SvImJ maintained relatively normal cardiac function, whereas C57BL/6J animals showed dramatic cardiac decompensation. Additionally, C3H/HeJ showed rapid and marked cardiac decompensation in response to esmolol infusion compared with effects of other strains. These findings demonstrate the complex effects of genetic divergence between inbred strains on cardiac function. These results may help inform analysis of gene ablation or transgenic studies and further demonstrate specific quantitative traits that could be useful in discovery of genetic modifiers relevant to cardiac health and disease.

Abstract 268: Strain-specific Cardiac Fibroblast Response to Isoproterenol-induced Cardiac Fibrosis

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Shuin Park ◽  
Sara Ranjbarvaziri ◽  
Fides Lay ◽  
Peng Zhao ◽  
Aldons J Lusis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Expression Profiles ◽  
Inbred Mouse ◽  
Gene Expression Profiles ◽  
Mouse Strains ◽  
Sequencing Analysis ◽  
Different Strains

Fibroblasts are a heterogeneous population of cells that function within the injury response mechanisms across various tissues. Despite their importance in pathophysiology, the effects of different genetic backgrounds on fibroblast contribution to the development of disease has yet to be addressed. It has previously been shown that mice in the Hybrid Mouse Diversity Panel, which consists of 110 inbred mouse strains, display a spectrum in severity of cardiac fibrosis in response to chronic treatment of isoproterenol (ISO). Here, we characterized cardiac fibroblasts (CFbs) from three different mouse strains (C57BL/6J, C3H/HeJ, and KK/HIJ) which exhibited varying degrees of fibrosis after ISO treatment. The select strains of mice underwent sham or ISO treatment via intraperitoneally-implanted osmotic pumps for 21 days. Masson’s Trichrome staining showed significant differences in fibrosis in response to ISO, with KK/HIJ mice demonstrating the highest levels, C3H/HeJ exhibiting milder levels, and C57BL/6J demonstrating little to no fibrosis. When CFbs were isolated and cultured from each strain, the cells demonstrated similar traits at the basal level but responded to ISO stimuli in a strain-specific manner. Likewise, CFbs demonstrated differential behavior and gene expression in vivo in response to ISO. ISO treatment caused CFbs to proliferate similarly across all strains, however, immunofluorescence staining showed differential levels of CFb activation. Additionally, RNA-sequencing analysis revealed unique gene expression profiles of all three strains upon ISO treatment. Our study depicts the phenotypic heterogeneity of CFbs across different strains of mice and our results suggest that ISO-induced cardiac fibrosis is a complex process that is independent of fibroblast proliferation and is mainly driven by the activation/inhibition of genes involved in pro-fibrotic pathways.

Use of immunological manipulations in studying genetically controlled responses to Leishmania donovani infection in mice

Parasitology ◽  
1984 ◽  
Vol 88 (4) ◽  
pp. 677-679 ◽  
Author(s):  
Jenefer M. Blackwell
Keyword(s):  
Immune System ◽  
Leishmania Donovani ◽  
Inbred Mouse ◽  
Parasitic Infection ◽  
Preceding Paper ◽  
Mouse Strains ◽  
Host Immune System ◽  
Inbred Mouse Strains

In the preceding paper Howard (p. 665) has given a very elegant presentation on ways in which the host immune system may be manipulated to provide valuable information about immunoregulation of parasitic infection in vivo. In our laboratory we have used some of the same manoeuvres to study immunoregulation of genetically controlled responses to Leishmania donovani infection in inbred mouse strains (Ulczak & Blackwell, 1983; Crocker, Blackwell & Bradley, 1984). As has been Howard's experience, the results obtained have not always been as one might have predicted at the outset.

scholarly journals Structural and functional studies of the early T lymphocyte activation 1 (Eta-1) gene. Definition of a novel T cell-dependent response associated with genetic resistance to bacterial infection.

1989 ◽  
Vol 170 (1) ◽  
pp. 145-161 ◽  
Author(s):  
R Patarca ◽  
G J Freeman ◽  
R P Singh ◽  
F Y Wei ◽  
T Durfee ◽  
...  
Keyword(s):  
T Cell ◽  
Bacterial Infection ◽  
T Lymphocyte ◽  
Inbred Mouse ◽  
Genetic Resistance ◽  
Lymphocyte Activation ◽  
Cellular Adhesion ◽  
Mouse Strains ◽  
T Lymphocyte Activation

We describe a murine cDNA, designated Early T lymphocyte activation 1 (ETA-1) which is abundantly expressed after activation of T cells. Eta-1 encodes a highly acidic secreted product having structural features of proteins that bind to cellular adhesion receptors. The Eta-1 gene maps to a locus on murine chromosome 5 termed Ric that confers resistance to infection by Rickettsia tsutsugamushi (RT), an obligate intracellular bacterium that is the etiological agent for human scrub typhus. With one exception, inbred mouse strains that expressed the Eta-1a allele were resistant to RT infection (RicR), and inbred strains expressing the Eta-1b allele were susceptible (RicS). These findings suggest that Eta-1 is the gene inferred from previous studies of the Ric locus (5). Genetic resistance to RT infection is associated with a strong Eta-1 response in vivo and inhibition of early bacterial replication. Eta-1 gene expression appears to be part of a surprisingly rapid T cell-dependent response to bacterial infection that may precede classical forms of T cell-dependent immunity.

scholarly journals Susceptibility to tumors induced by polyoma virus is conferred by an endogenous mouse mammary tumor virus superantigen.

1995 ◽  
Vol 181 (5) ◽  
pp. 1683-1692 ◽  
Author(s):  
A E Lukacher ◽  
Y Ma ◽  
J P Carroll ◽  
S R Abromson-Leeman ◽  
J C Laning ◽  
...  
Keyword(s):  
T Cells ◽  
Mammary Tumor ◽  
Inbred Mouse ◽  
Dominant Gene ◽  
Polyoma Virus ◽  
Mouse Strains ◽  
Cell Repertoire ◽  
Inherited Susceptibility ◽  
Mouse Mammary Tumor

A dominant gene carried in certain inbred mouse strains confers susceptibility to tumors induced by polyoma virus. This gene, designated Pyvs, was defined in crosses between the highly susceptible C3H/BiDa strain and the highly resistant but H-2k-identical C57BR/cdJ strain. The resistance of C57BR/cdJ mice is overcome by irradiation, indicating an immunological basis. In F1 x C57BR/cdJ backcross mice, tumor susceptibility cosegregates with Mtv-7, a mouse mammary tumor provirus carried by the C3H/BiDa strain. This suggests that Pyvs might encode the Mtv-7 superantigen (SAG) and abrogate polyoma tumor immunosurveillance through elimination of T cells bearing specific V beta domains. DNA typing of 110 backcross mice showed no evidence of recombination between Pyvs and Mtv-7. Strongly biased usage of V beta 6 by polyoma virus-specific CD8+ cytotoxic T lymphocytes in C57BR/cdJ mice implicates T cells bearing this Mtv-7 SAG-reactive V beta domain as critical anti-polyoma tumor effector cells in vivo. These results indicate identity between Pyvs and Mtv-7 sag, and demonstrate a novel mechanism of inherited susceptibility to virus-induced tumors based on effects of an endogenous superantigen on the host's T cell repertoire.

scholarly journals Real-time analysis of T cell receptors in naive cells in vitro and in vivo reveals flexibility in synapse and signaling dynamics

2010 ◽  
Vol 207 (12) ◽  
pp. 2733-2749 ◽  
Author(s):  
Rachel S. Friedman ◽  
Peter Beemiller ◽  
Caitlin M. Sorensen ◽  
Jordan Jacobelli ◽  
Matthew F. Krummel
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Real Time ◽  
T Cell Activation ◽  
Valuable Insight ◽  
Time Dynamics ◽  
Insight Into

The real-time dynamics of the T cell receptor (TCR) reflect antigen detection and T cell signaling, providing valuable insight into the evolving events of the immune response. Despite considerable advances in studying TCR dynamics in simplified systems in vitro, live imaging of subcellular signaling complexes expressed at physiological densities in intact tissues has been challenging. In this study, we generated a transgenic mouse with a TCR fused to green fluorescent protein to provide insight into the early signaling events of the immune response. To enable imaging of TCR dynamics in naive T cells in the lymph node, we enhanced signal detection of the fluorescent TCR fusion protein and used volumetric masking with a second fluorophore to mark the T cells expressing the fluorescent TCR. These in vivo analyses and parallel experiments in vitro show minimal and transient incorporation of TCRs into a stable central supramolecular activating cluster (cSMAC) structure but strong evidence for rapid, antigen-dependent TCR internalization that was not contingent on T cell motility arrest or cSMAC formation. Short-lived antigen-independent TCR clustering was also occasionally observed. These in vivo observations demonstrate that varied TCR trafficking and cell arrest dynamics occur during early T cell activation.

scholarly journals ANTIBODY RESPONSE OF INBRED MOUSE STRAINS TO ORDERED TETRAPEPTIDES OF TYROSINE AND GLUTAMIC ACID ATTACHED TO MULTICHAIN POLYALANINE OR POLYPROLINE

1974 ◽  
Vol 140 (2) ◽  
pp. 349-355 ◽  
Author(s):  
Edna Mozes ◽  
Michal Schwartz ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Glutamic Acid ◽  
Inbred Mouse ◽  
Cross Reactivity ◽  
Antigenic Determinants ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Linked Gene ◽  
Random Peptide ◽  
Synthetic Polypeptide

Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.

scholarly journals Immunosuppressive factor(s) specific for L-glutamic acid(50)-L- tyrosine(50) (GT). II. Presence of I-J determinants on the GT-suppressive factor

1977 ◽  
Vol 146 (1) ◽  
pp. 287-292 ◽  
Author(s):  
J Theze ◽  
C Waltenbaugh ◽  
ME Dorf ◽  
B Benacerraf
Keyword(s):  
T Cells ◽  
Glutamic Acid ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Antibody Responses ◽  
Mouse Strains ◽  
Suppressor T Cells ◽  
Suppressor Factor

The responses to the synthetic antigens, L-glutamic acid(60)-L- alanine(30)-L-tyrosine(10) (GAT) and L-glutamic acid(50)-L-tyrosine(50) (GT) are controlled by genes in the I region of the mouse H-2 complex (1-3). Preimmunization of the mice bearing the H-2(p,q,s) nonresponder haplotypes with GAT stimulates the development of suppressor T cells that inhibit in vivo or in vitro antibody responses to GAT complexed to the immunogenic carrier, methylated bovine serum albumin (GAT-MBSA) (4). The copolymer GT is not immunogenic in any inbred mouse strain tested, and has a suppressive effect on the antibody responses to GT-MBSA in mouse strains bearing the H-2(d,f,k,s) haplotypes; suppressor T cells have been demonstrated to be responsible for specific GT suppression (3). We have obtained specific suppressive extracts from thymus and spleen cells of GAT-or GT-primed suppressor strains (5,6). The specific suppressive T-cell factors in the active extracts have been characterized (6,7) and appear similar to the carrier-specific suppressor factor described by Tada and Taniguchi (8). These products belong to a family of newly identified molecules coded for by the I region of the H-2 complex with affinity for antigen and helper (9,10) or suppressive (5-8) regulatory activity on the immune response. Recently, Tada et al. have reported that the keyhole limpet hemocyanin (KLH)-specific suppressor factor is coded for by the I-J subregion of the H-2 complex (11). We now demonstrate also that a GT-specific suppressor factor extracted from the spleens and thymuses of B10.BR (H-2(k)) mice bears determinants controlled by the I-J subregion of the H-2 complex.

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