scholarly journals THE EFFECT OF ANTI-LYMPHOCYTE GLOBULIN ON CELL-MEDIATED RESISTANCE TO INFECTION

1969 ◽  
Vol 129 (5) ◽  
pp. 993-1012 ◽  
Author(s):  
G. B. Mackaness ◽  
William C. Hill

The specificity of anti-lymphocyte globulin (ALG) has been used to analyze an immune mechanism which is mediated by immunologically committed lymphoid cells to the apparent exclusion of humoral antibody. Rabbit antimouse lymphocyte globulin completely suppressed the immunity which can be passively transferred with Listeria-immune lymphoid cells from actively infected donors. When prospective donors were given a single dose of 1.0 mg of ALG, it remained active against immune lymphoid cells transferred 24 hr later; yet immune cells in the spleens of donors could not be inactivated in situ by even larger doses of ALG given 24 hr prior to cell harvest. In keeping with this finding, the immunity to reinfection with Listeria was not suppressed by a single dose of ALG, indicating that the immunologically active cells in the spleen are not accessible to intravenously administered ALG. On the other hand, protracted treatment with ALG did abolish most of the memory of a previous infection in intact animals. From this and other evidence, it was concluded that immunologically committed cells are vulnerable to attack by ALG only if they circulate. While in circulation, they make contact both with ALG and the phagocytic elements of the reticuloendothelial system which appear to be responsible for their destruction. Four lines of evidence indicated that the suppression of anti-Listeria resistance with ALG depends upon destruction of immune lymphoid cells and not to any action it has on host macrophages. It is possible to infer from this that immunity to L. monocytogenes depends upon a two cell system in which the donor lymphoid cells provide the immunological reactivity to the organism and recipient macrophages provide the mechanism through which resistance is expressed. Accompanying papers provide additional support for this view, and reasons for believing that delayed-type hypersensitivity and acquired cellular resistance are mediated by the same population of immunologically committed lymphoid cells.

Author(s):  
Arash Alex Mazhari ◽  
Randall Ticknor ◽  
Sean Swei ◽  
Stanley Krzesniak ◽  
Mircea Teodorescu

AbstractThe sensitivity of additive manufacturing (AM) to the variability of feedstock quality, machine calibration, and accuracy drives the need for frequent characterization of fabricated objects for a robust material process. The constant testing is fiscally and logistically intensive, often requiring coupons that are manufactured and tested in independent facilities. As a step toward integrating testing and characterization into the AM process while reducing cost, we propose the automated testing and characterization of AM (ATCAM). ATCAM is configured for fused deposition modeling (FDM) and introduces the concept of dynamic coupons to generate large quantities of basic AM samples. An in situ actuator is printed on the build surface to deploy coupons through impact, which is sensed by a load cell system utilizing machine learning (ML) to correlate AM data. We test ATCAM’s ability to distinguish the quality of three PLA feedstock at differing price points by generating and comparing 3000 dynamic coupons in 10 repetitions of 100 coupon cycles per material. ATCAM correlated the quality of each feedstock and visualized fatigue of in situ actuators over each testing cycle. Three ML algorithms were then compared, with Gradient Boost regression demonstrating a 71% correlation of dynamic coupons to their parent feedstock and provided confidence for the quality of AM data ATCAM generates.


1969 ◽  
Vol 129 (6) ◽  
pp. 1235-1246 ◽  
Author(s):  
Esther F. Hays

Work has been presented which suggests that thymus epithelial reticular cells are not effective in restoring the microscopic morphology of lymphoid tissues and their immunologic capacities. They function in recruiting precursors of thymus lymphocytes from the host animals to produce an organ which, after it becomes architecturally normal, can reconstitute the defective host. Intact thymus grafts in situ from 10–14 days, but not for shorter periods of time, have been shown to result in a return toward normal of these two parameters. Evidence is offered to show that few dividing cellular components in the lymphoid tissue originate from the thymus remnant grafts, and that a minor cellular component is contributed by the intact grafts. These data support the concept that the structural and functional development of the lymphatic tissue in thymectomized animals is dependent on thymus lymphoid cells and/or their products, and that the epithelial-reticular cells do not have a direct action in peripheral lymphoid reconstitution.


1995 ◽  
Vol 48 (3) ◽  
pp. M158-M164 ◽  
Author(s):  
C Carvalho ◽  
M Telhada ◽  
M do Carmo-Fonseca ◽  
L Parreira

2021 ◽  
Author(s):  
Jin Gao ◽  
Laura Klenow ◽  
Lisa Parsons ◽  
Tahir Malik ◽  
Je-Nie Phue ◽  
...  

Supplementing influenza vaccines with recombinant neuraminidase (rNA) antigens remains a promising approach for improving the suboptimal vaccine efficacy. However, correlations among rNA designs, properties, and protection have not been systematically investigated. Here, we performed a comparative analysis of several rNAs produced using the baculovirus/insect cell system. The rNAs were designed with different tetramerization motifs and NA domains from a recent H1N1 vaccine strain (A/Brisbane/02/2018) and were compared for enzymatic property, antigenicity, stability, and protection in mice. We found that distinct enzymatic properties are associated with rNAs containing the NA head-domain versus the full-ectodomain, formation of higher order rNA oligomers is tetramerization domain-dependent, whereas protective efficacy is more contingent on the combination of the tetramerization and NA domains. Following single-dose immunizations, a rNA possessing the full-ectodomain and the tetramerization motif from the human vasodilator-stimulated phosphoprotein provided much better protection than a rNA with ∼10-fold more enzymatically active molecules that is comprised of the head-domain and the same tetramerization motif. In contrast, these two rNA designs provided comparable protection when the tetramerization motif from the tetrabrachion protein was used instead. These findings demonstrate that individual rNAs should be thoroughly evaluated for vaccine development, as the heterologous domain combination can result in rNAs with similar key attributes but vastly differ in protection. IMPORTANCE For several decades it has been proposed that influenza vaccines could be supplemented with recombinant neuraminidase (rNA) to improve the efficacy. However, some key questions for manufacturing stable and immunogenic rNA remain to be answered. We show here that the tetramerization motifs and NA domains included in the rNA construct design can have a profound impact on the biochemical, immunogenic and protective properties. We also show that the single-dose immunization regimen is more informative for assessing the rNA immune response and protective efficacy, which is surprisingly more dependent on the specific combination of NA and tetramerization domains than common attributes for evaluating NA. Our findings may help to optimize the design of rNAs that can be used to improve or develop influenza vaccines.


Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 295-297 ◽  
Author(s):  
Patrick M. Reagan ◽  
Andrew Davies

Abstract A 60-year-old female presented with abdominal pain and distension. Following computed tomography scans of the abdomen and pelvis, she was taken urgently to the operating room, with the belief that she had appendicitis with perforation. At laparotomy, the findings were consistent with an ovarian carcinoma; there was extensive infiltration of the ovary, bowel, and omental deposits. Cytoreductive surgery was performed including total abdominal hysterectomy and bilateral salpingo-oophorectomy. The final pathology, however, revealed infiltration with medium-sized atypical lymphoid cells positive for CD20, CD10, MYC, BLC2, and BCL6 by immunohistochemistry. MYC and BCL2 translocations were identified by fluorescence in situ hybridization consistent with a diagnosis of high-grade B-cell lymphoma with rearrangements of MYC and BCL2. With the current data available, what is the optimal treatment of this patient?


1989 ◽  
Vol 169 (5) ◽  
pp. 1841-1846 ◽  
Author(s):  
E P Benditt ◽  
R L Meek

Three homologous genes that code for three related proteins comprise the serum amyloid A (SAA) family in the mouse. Endotoxin induces equally vigorous expression of mRNAs for the three SAA genes in liver. In extrahepatic tissues SAA1 and/or SAA2 mRNAs have been found only in kidney and intestine, however, SAA3 is expressed in all extrahepatic tissues thus far examined. This observation raised the question: is SAA3 mRNA expressed by a single cell system dispersed throughout all tissues, or by differentiated cells of each tissue? This question was explored in various tissues by in situ hybridization with a single-stranded cRNA probe specific for SAA3 mRNA. We found expression in the liver of SAA3 mRNA by other cells as well as by hepatocytes. A common feature among extrahepatic tissues was SAA3 mRNA expression in adipocytes. SAA3 mRNA was also found in two nonadipose cells, Leydig cells of the testis, and some of the cells located in parafollicular zones of the spleen.


1989 ◽  
Vol 169 (5) ◽  
pp. 1565-1581 ◽  
Author(s):  
C L Cooper ◽  
C Mueller ◽  
T A Sinchaisri ◽  
C Pirmez ◽  
J Chan ◽  
...  

Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.


2001 ◽  
Vol 72 (2) ◽  
pp. 1289 ◽  
Author(s):  
Tetsu Watanuki ◽  
Osamu Shimomura ◽  
Takehiko Yagi ◽  
Tadashi Kondo ◽  
Maiko Isshiki

Parasitology ◽  
1969 ◽  
Vol 59 (3) ◽  
pp. 497-503 ◽  
Author(s):  
A. D. Donald ◽  
J. K. Dineen ◽  
D. B. Adams

An experiment has been conducted to examine the effects of discontinuous infection with H. contortus in sheep on the development of resistance to infection. When sheep were given four doses of 3000 larvae at fortnightly intervals and these sensitizing infections were removed on day 56, there was no evidence of resistance at that time nor of any residual effect of the sensitizing infections on the response to challenge at day 140. When, however, the sensitizing infections were permitted to persist until day 132, there was strong resistance to the establishment of a challenge infection whether or not the sensitizing worm burden was removed prior to challenge, and, in the case of superimposed challenge, resistance was coupled with rejection of most of the sensitizing population. When a single infection with 3000 larvae was followed 22 days later with a further single dose of 3000 larvae, there was no evidence of resistance whether or not the first infection was removed with anthelmintic. If the interval between two doses of 3000 larvae was extended to 76 days there was resistance to the establishment of the second dose if this was superimposed on the first, but not if the first infection was removed 8 days prior to the second dose.It is suggested that the manifestations of resistance appear in a sequence of (i) resistance only to a superimposed infection, followed by (ii) resistance to a challenge infection in the presence or absence of a previously existing worm burden, coupled in the former case with rejection of much of the existing population. This sequence could be related crudely to a product of larval dose and time. Although larval dose and time were to some extent confounded in the design of the experiment strong resistance was associated with prolonged uninterrupted infection.


2020 ◽  
Vol 319 ◽  
pp. 438-449 ◽  
Author(s):  
Lin Hou ◽  
Yingshan Yan ◽  
Chunyu Tian ◽  
Qianxiao Huang ◽  
Xiangjing Fu ◽  
...  

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