Phagosomal acidification: measurement, manipulation and functional consequences

2007 ◽  
Vol 35 (5) ◽  
pp. 1083-1087 ◽  
Author(s):  
B.E. Steinberg ◽  
K.K. Huynh ◽  
S. Grinstein
Keyword(s):  
Electrical Potential ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Central Position ◽  
Protonmotive Force ◽  
Phagosome Maturation ◽  
Critical Determinant ◽  
Functional Consequences ◽  
Phagosomal Membrane

Phagocytosis holds a central position in the development of a successful innate immune response and in the initiation of the corresponding adaptive response. The destruction of invading pathogens and the presentation of their antigens to lymphoid cells require acidification of the phagosomal lumen. The present review discusses the mechanism of phagosome acidification, with particular reference to the two components of the protonmotive force: the chemical (pH) gradient and the electrical potential across the phagosomal membrane. A method for the in situ measurement of the electrical potential across the phagosomal membrane is described. In addition, we discuss the finding that acidification is not only a consequence, but also a critical determinant of phagosome maturation. Luminal acidification appears to function as a timing device controlling the transition between early and late phagosomes.

scholarly journals THE EFFECT OF EPITHELIAL REMNANT AND WHOLE ORGAN GRAFTS OF THYMUS ON THE RECOVERY OF THYMECTOMIZED IRRADIATED MICE

1969 ◽  
Vol 129 (6) ◽  
pp. 1235-1246 ◽  
Author(s):  
Esther F. Hays
Keyword(s):  
Direct Action ◽  
Lymphoid Cells ◽  
Lymphoid Tissues ◽  
Functional Development ◽  
Reticular Cells ◽  
Microscopic Morphology ◽  
Two Parameters ◽  
A Minor ◽  
Cellular Components

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.

scholarly journals In situ visualisation of immunoglobulin genes in normal and malignant lymphoid cells

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

How the parasitic bacterium Legionella pneumophila modifies its phagosome and transforms it into rough ER: implications for conversion of plasma membrane to the ER membrane

2001 ◽  
Vol 114 (24) ◽  
pp. 4637-4650 ◽  
Author(s):  
Lewis G. Tilney ◽  
Omar S. Harb ◽  
Patricia S. Connelly ◽  
Camenzind G. Robinson ◽  
Craig R. Roy
Keyword(s):  
Legionella Pneumophila ◽  
Mitochondrial Membranes ◽  
Macrophage Infection ◽  
Thin Sections ◽  
Stage Process ◽  
Legionnaires Disease ◽  
Rough Er ◽  
Membrane Changes ◽  
Phagosomal Membrane

Within five minutes of macrophage infection by Legionella pneumophila, the bacterium responsible for Legionnaires’ disease, elements of the rough endoplasmic reticulum (RER) and mitochondria attach to the surface of the bacteria-enclosed phagosome. Connecting these abutting membranes are tiny hairs, which are frequently periodic like the rungs of a ladder. These connections are stable and of high affinity - phagosomes from infected macrophages remain connected to the ER and mitochondria (as they were in situ) even after infected macrophages are homogenized. Thin sections through the plasma and phagosomal membranes show that the phagosomal membrane is thicker (72±2 Å) than the ER and mitochondrial membranes (60±2 Å), presumably owing to the lack of cholesterol, sphingolipids and glycolipids in the ER. Interestingly, within 15 minutes of infection, the phagosomal membrane changes thickness to resemble that of the attached ER vesicles. Only later (e.g. after six hours) does the ER-phagosome association become less frequent. Instead ribosomes stud the former phagosomal membrane and L. pneumophila reside directly in the rough ER. Examination of phagosomes of various L. pneumophila mutants suggests that this membrane conversion is a four-stage process used by L. pneumophila to establish itself in the RER and to survive intracellularly. But what is particularly interesting is that L. pneumophila is exploiting a poorly characterized naturally occuring cellular process.

scholarly journals Influenza virus N-linked glycosylation and innate immunity

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Ian A. York ◽  
James Stevens ◽  
Irina V. Alymova
Keyword(s):  
Immune Responses ◽  
Evolutionary Dynamics ◽  
Analytical Techniques ◽  
Influenza Viruses ◽  
Innate Immune ◽  
Global Public Health ◽  
Innate Immune Responses ◽  
Critical Determinant ◽  
Public Health Challenge ◽  
Seasonal Epidemics

AbstractInfluenza viruses cause seasonal epidemics and sporadic pandemics in humans. The virus’s ability to change its antigenic nature through mutation and recombination, and the difficulty in developing highly effective universal vaccines against it, make it a serious global public health challenge. Influenza virus’s surface glycoproteins, hemagglutinin and neuraminidase, are all modified by the host cell’s N-linked glycosylation pathways. Host innate immune responses are the first line of defense against infection, and glycosylation of these major antigens plays an important role in the generation of host innate responses toward the virus. Here, we review the principal findings in the analytical techniques used to study influenza N-linked glycosylation, the evolutionary dynamics of N-linked glycosylation in seasonal versus pandemic and zoonotic strains, its role in host innate immune responses, and the prospects for lectin-based therapies. As the efficiency of innate immune responses is a critical determinant of disease severity and adaptive immunity, the study of influenza glycobiology is of clinical as well as research interest.

scholarly journals Current treatment of double hit and double expressor lymphoma

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 295-297 ◽  
Author(s):  
Patrick M. Reagan ◽  
Andrew Davies
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Total Abdominal Hysterectomy ◽  
Abdominal Hysterectomy ◽  
Current Treatment ◽  
Current Data ◽  
Lymphoid Cells ◽  
High Grade ◽  
Computed Tomography Scans

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?

scholarly journals Adipocytes, Innate Immunity and Obesity: A Mini-Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Alecia M. Blaszczak ◽  
Anahita Jalilvand ◽  
Willa A. Hsueh
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Immune Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Lymphoid Cells ◽  
Innate Immune Cells ◽  
Adaptive Immune

The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.

Integrin switching regulates normal trophoblast invasion

Development ◽  
1994 ◽  
Vol 120 (12) ◽  
pp. 3657-3666 ◽  
Author(s):  
C.H. Damsky ◽  
C. Librach ◽  
K.H. Lim ◽  
M.L. Fitzgerald ◽  
M.T. McMaster ◽  
...  
Keyword(s):  
First Trimester ◽  
Uterine Wall ◽  
Trophoblast Invasion ◽  
Collagen Type Iv ◽  
Fibronectin Receptor ◽  
Type Iv ◽  
Invasive Capacity ◽  
Functional Consequences

Cells invade extracellular matrices in a regulated manner at specific times and places during normal development. A dramatic example is trophoblast invasion of the uterine wall. Previous studies have shown that differentiation of trophoblasts to an invasive phenotype is accompanied by temporally and spatially regulated switching of their integrin repertoire. In the first trimester human placenta, alpha 6 integrins are restricted to cytotrophoblast (CTB) stem cells and downregulated in invasive CTBs, whereas alpha 5 beta 1 and alpha 1 beta 1 integrins are upregulated in differentiating and invasive CTBs. The goal of the present study was to determine whether these changes have functional consequences for CTB invasiveness. Using an in vitro invasion model, we determined first that aggregates of invading first trimester CTBs in vitro undergo the same pattern of integrin switching as was observed in situ, thereby validating the utility of the model. We then showed that antibody perturbation of interactions involving laminin or collagen type IV and their integrin alpha 1/beta 1 receptor inhibited invasion by CTBs, whereas perturbing interactions between fibronectin and the alpha 5/beta 1 fibronectin receptor accelerated invasion. Finally, we report that later gestation CTBs, which display greatly decreased invasive capacity, are also unable to upregulate alpha 1 beta 1 complexes, providing further evidence that this integrin is critical for CTB invasion. This gestational regulation is transcriptional. These data indicate that integrin switching observed during differentiation in situ has significant functional consequences for CTB invasion. The data suggest further that differentiating CTBs upregulate counterbalancing invasion-accelerating and invasion-restraining adhesion mechanisms. We propose that this contributes to regulating the depth of CTB invasion during normal implantation.

Electrophysiology of the in situ contractile vacuole complex of Paramecium reveals its membrane dynamics and electrogenic site during osmoregulatory activity.

1998 ◽  
Vol 201 (3) ◽  
pp. 451-460 ◽  
Author(s):  
T Tominaga ◽  
R D Allen ◽  
Y Naitoh
Keyword(s):  
Proton Pump ◽  
Electrical Potential ◽  
Membrane Dynamics ◽  
Contractile Vacuole ◽  
Vacuole Membrane ◽  
Input Capacitance ◽  
Linear Current ◽  
Relationship Of ◽  
Voltage Relationship

In the freshwater protozoan Paramecium multomicronucleatum, excess cytosolic water, acquired osmotically, is segregated and expelled to the cell exterior through the activity of the contractile vacuole complex. This process keeps the cell volume constant. The electrophysiological parameters of the organelle were measured in situ using a fine-tipped microelectrode inserted into the contractile vacuole, the exocytotic vesicle of the organelle to which the segregated fluid is transported before being expelled to the exterior. The input capacitance decreased markedly immediately before fluid expulsion and regained its previous value when fluid filling resumed after fluid expulsion. This change in the capacitance proved that the contractile vacuole became disconnected from its radial arms, which project from the vacuole, before fluid expulsion occurred and then reconnected with the arms after fluid expulsion. A positive electrical potential was recorded from the contractile vacuole only when it was connected to the radial arms. This implies that the electrogenic mechanism resides exclusively in the radial arms and supports the idea that the decorated spongiomes, V-type proton-pump-covered terminal tubules of the radial arms that end blindly in the cytosol, are electrogenic. The linear current­voltage relationship of the contractile vacuole membrane also implies that few voltage-activated ion channels are present in the membrane. To explain the movement of water into the contractile vacuole complex, we favour the hypothesis that the potential generated across the decorated spongiome membrane can be used to drive counter-anions from the cytosol into the lumen of the complex. The anions could then act as an osmolite to pull cytosolic water into the lumen of the organelle.

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