THE THYMUS AND OTHER LYMPHOID TISSUES IN CONGENITAL AGAMMAGLOBULINEMIA

PEDIATRICS ◽  
1963 ◽  
Vol 32 (4) ◽  
pp. 517-530 ◽  
Author(s):  
David Gitlin ◽  
John M. Craig
Keyword(s):  
Bacterial Infections ◽  
Plasma Cells ◽  
Lymphoid Tissues ◽  
Normal Numbers ◽  
Primary Defect ◽  
Susceptibility To Infection ◽  
Resistance To Infection ◽  
Lymphoid Structures ◽  
Leukocyte Response ◽  
Increased Susceptibility

Patients with congenital agammaglobulinemia may be separated clinically and pathologically into two groups. One group manifests a persistent lymphopenia and is characterized clinically by an unremitting course marked by pneumonia, moniliasis, and other infections usually beginning in the first three months of life and, thus far, terminating fatally during the patient's infancy. These patients have thymic alymphoplasia and lymphocytic hypoplasia of their tissues: the thymus is rudimentary, and the other lymphoid structures contain only sparse populations of small lymphocytes. The thymic alymphoplasia and general deficiency in small lymphocytes appear to be inherited characteristics and the evidence suggests that the primary defect is thymic alymphoplasia which results in generalized lymphocytic hypoplasia including lymphopenia. The second group of patients often has a later onset and a more intermittent course of bacterial infections, a variable leukocyte response marked only occasionally by transitory lymphopenia; their lymphoid organs including the thymus contain more nearly normal numbers of lymphocytes. Plasma cells and germinal follicles are absent from the tissues of both groups of patients, but the marked generalized paucity of small lymphocytes in these patients with thymic alymphoplasia results in an increased susceptibility to infection beyond that seen in nonlymphopenic agammaglobu-linemia. Whatever the exact contribution of the small lymphocyte to resistance to infection, it appears to be significant and its loss is not replaced by γ-globulin therapy.

Infection Following Splenectomy in Infants and Children

PEDIATRICS ◽  
1958 ◽  
Vol 22 (3) ◽  
pp. 574-574
Keyword(s):  
North Carolina ◽  
Infants And Children ◽  
Younger Patients ◽  
Susceptibility To Infection ◽  
Serious Infections ◽  
Resistance To Infection ◽  
Effect Of Splenectomy ◽  
In Infants And Children ◽  
Increased Susceptibility

This paper presents an analysis of the experience at Duke Hospital in Durham, North Carolina, regarding the effect of splenectomy on susceptibility to infection. Of 46 patients who had been subjected to splenectomy, 7 developed serious infections after the operation; 5 of these 7 patients were under 1 year of age at the time of splenectomy. It appeared that the younger patients were more susceptible to this complication. Five of the seven patients had diseases which are known to be associated with an increased susceptibility to infection. Therefore it appeared that the effect of splenectomy on decrease of resistance to infection was more conspicuous in those whose basic disease was associated with proneness to infections.

scholarly journals REVERSIBLE CHANGES IN THE SUSCEPTIBILITY OF MICE TO BACTERIAL INFECTIONS

1956 ◽  
Vol 104 (1) ◽  
pp. 67-84 ◽  
Author(s):  
Russell W. Schaedler ◽  
René J. Dubos
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Susceptibility To Infection ◽  
Complete Diet ◽  
Infective Dose ◽  
Time Of Infection ◽  
Time Variations ◽  
Nutritional Disturbances ◽  
Short Time ◽  
Increased Susceptibility

A study has been made of the time variations in the susceptibility of albino mice to experimental infections with Klebsiella pneumoniae, Staphylococcus aureus, and Mycobacterium tuberculosis. Susceptibility to infection was determined by two criteria: (a) mortality rates following intravenous injection of a known infective dose; (b) numbers of bacterial colonies that could be recovered from the tissues of the infected animals at various times after infection. When measured in terms of either one of these two criteria, susceptibility was consistently modified by temporary deprivation of food, and by various changes in the composition of the diet. Increase in susceptibility to infection could be detected within a few hours to a few days depending upon the nature and intensity of the nutritional disturbance imposed upon the animal. Under the proper conditions, return to a normal state of resistance could also occur within a very short time. There was commonly observed an explosive bacterial multiplication in mice receiving the infective dose shortly after being subjected to nutritional disturbances. In the case of infection with Klebsiella pneumoniae, however, this phase of increased susceptibility was often followed a few hours later by one during which the numbers of living bacteria that could be recovered from the various organs fell to a very low level. Many of the animals which had exhibited severe but transient bacteriemia recovered rapidly and survived the infection. Mice rendered more susceptible to infection by being fed deficient diets progressively recovered their normal resistance while being kept on the same inadequate regimens. This adaptation occurred even though the weight of the animals on these regimens remained much lower than the weight of the animals fed a complete diet ad lib. The weight of the animal at the time of infection appeared to have little bearing on susceptibility. However, susceptibility consistently increased during the periods while the animals were losing weight—whatever the cause of the weight loss. The facts disclosed in the present study, as well as findings reported by other investigators, make clear that profound changes in susceptibility to infection can be brought about by varied non-specific procedures. These changes can occur within very short periods of time and are often rapidly reversible.

scholarly journals EFFECT OF DIETARY PROTEINS AND AMINO ACIDS ON THE SUSCEPTIBILITY OF MICE TO BACTERIAL INFECTIONS

1958 ◽  
Vol 108 (1) ◽  
pp. 69-81 ◽  
Author(s):  
René J. Dubos ◽  
Russell W. Schaedler
Keyword(s):  
Amino Acids ◽  
Bacterial Infections ◽  
Bacterial Pathogen ◽  
Essential Amino Acids ◽  
Dietary Factors ◽  
Intravenous Route ◽  
Mycobacterium Fortuitum ◽  
Amino Acid Supplementation ◽  
Susceptibility To Infection ◽  
Resistance To Infection

Groups of young albino mice were fed continuously four different types of diets and were compared with regard to (1) rate of weight gain; (2) resistance to experimental bacterial infections. The protein content of the four diets was as follows: (a) pellets: a minimum of 21 per cent "crude" protein (according to the manufacturer); (b) diet 20 C: 20 per cent casein; (c) diet 8 C: 8 per cent casein; (d) diet 8 C + AA: 8 per cent casein supplemented with 12 per cent of a mixture of essential amino acids. All diets provided an adequate supply of minerals and vitamins. They were administered ad lib. Three strains of pathogens virulent for mice were used for the infection tests, namely: Staphylococcus aureus, Mycobacterium fortuitum, and Mycobacterium tuberculosis bovis. The bacteria were injected by the intravenous route. The experimental regimens were begun at different times before infection, and were continued until death of the animal, or until termination of the experiment. It was found that mice on the 8 C diet exhibited much greater susceptibility to infection than did mice on the 20 C diet; mice receiving pellets were intermediate between these two groups. The infection-enhancing effect of the 8 C diet could be entirely corrected by amino acid supplementation (diet 8 C + AA). Indeed, mice fed diet 8 C + AA proved the most resistant to infection. The fact that animals fed pellets (which contain a minimum of 21 per cent protein) consistently died faster following infection than did animals fed diets 20 C or 8 C + AA suggests that qualitative characteristics of the protein in the regimen are as important as the quantity of protein fed in determining susceptibility to infection. The differences in susceptibility exhibited by the mice on the four experimental diets were the same whatever the species of bacterial pathogen used for the infection test, the size of the infective dose, and the duration of the disease. There was no apparent relation between the effects of the diets on the weight curves of the animals, and on resistance to infection. Mice on diet 8 C (which were most susceptible) gained weight as rapidly as those on 20 C and more rapidly than those fed 8 C + AA (which were most resistant). All the tests reported in the present paper were carried out with young mice, which were placed on experimental diets within 1 to 2 weeks after weaning. Preliminary experiments suggest that the relation between dietary factors and susceptibility to infection was more difficult to bring out in older animals. There was evidence also that this relation was most apparent during the first weeks that the animals were fed the experimental diets, and became less striking after several weeks.

Macrophage Motility Dysfunction in a Patient with Recurrent Infections.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3835-3835
Author(s):  
Paul T. Jubinsky ◽  
Mary Short ◽  
Anthony Ashton ◽  
Diane Cox ◽  
Fiona Pixley
Keyword(s):  
Peripheral Blood ◽  
Bacterial Infections ◽  
Cell Function ◽  
Time Lapse ◽  
Early Age ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Susceptibility To Infection ◽  
Normal Individuals ◽  
Increased Susceptibility

Abstract Three members of a family with normal parents had a common constellation of findings that included absent corpus callosum and recurrent bacterial infections. The older male and female siblings both died from infection at an early age. The patient’s CBC was significant for elevated numbers of monocytes that were large and vacuolated. Her T- and B-cell function was normal. These preliminary findings suggested a defect in innate immunity. Evaluation of the patient’s peripheral blood monocytes by flow cytometry showed normal size and maturity. Phagocytosis and activation of peripheral blood derived macrophages by cytokines were also similar to controls. In contrast, the patient’s cultured macrophages were significantly more spread than those from normal individuals and contained a disordered actin cytoskeleton when cultured on fibronectin. The ability of the macrophage to transmigrate across an endothelial cell barrier was impaired. However examination by time-lapse videomicroscopy showed that the mutant macrophages had increased protrusional activity and movement. This is the first report describing a genetic macrophage motility disorder that results in an increased susceptibility to infection.

scholarly journals Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis

2006 ◽  
Vol 203 (6) ◽  
pp. 1407-1412 ◽  
Author(s):  
Maria Lara-Tejero ◽  
Fayyaz S. Sutterwala ◽  
Yasunori Ogura ◽  
Ethan P. Grant ◽  
John Bertin ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Proinflammatory Cytokines ◽  
Bacterial Infections ◽  
Oral Infection ◽  
Susceptibility To Infection ◽  
Caspase 1 ◽  
Increased Susceptibility

Caspase-1 is activated by a variety of stimuli after the assembly of the “inflammasome,” an activating platform made up of a complex of the NOD-LRR family of proteins. Caspase-1 is required for the secretion of proinflammatory cytokines, such as interleukin (IL)-1β and IL-18, and is involved in the control of many bacterial infections. Paradoxically, however, its absence has been reported to confer resistance to oral infection by Salmonella typhimurium. We show here that absence of caspase-1 or components of the inflammasome does not result in resistance to oral infection by S. typhimurium, but rather, leads to increased susceptibility to infection.

scholarly journals PRODUCTION OF A RUNTING SYNDROME AND SELECTIVE γA DEFICIENCY IN MICE BY THE ADMINISTRATION OF ANTI-HEAVY CHAIN ANTISERA

1973 ◽  
Vol 138 (1) ◽  
pp. 209-228 ◽  
Author(s):  
Robert A. Murgita ◽  
Carlos A. Mattioli ◽  
Thomas B. Tomasi
Keyword(s):  
Plasma Cells ◽  
Serum Antibody ◽  
Premature Death ◽  
Lymphoid Tissues ◽  
Normal Numbers ◽  
Essentially Normal ◽  
Γ Globulins ◽  
Antibody Titers ◽  
High Concentrations ◽  
Runting Syndrome

Conventional Swiss mice were treated from birth with intraperitoneal injections of anti-immunoglobulins in an attempt to create an experimental dysgammaglobulinemia. Mice treated with anti-γM were immunologically suppressed in all immunoglobulin classes as determined by serum antibody titers, splenic plaque-forming cells, serum immunoglobulin levels, and immunofluorescent analysis of plasma cells in lymphoid tissues. Treatment immediately after birth with high concentrations of anti-γM leads to a developmental arrest characterized by severe immunosuppression, failure to gain weight, and premature death. The pathogenesis of anti-γM runting syndrome is unknown. Animals similarly treated with anti-γG, anti-γA, or control normal goat or rabbit γ-globulins developed normally. The frequency of occurrence and severity of anti-γM-induced runting syndrome is dependent upon the concentration of anti-γM-globulin administered. Administration of anti-γA resulted in a selective γA deficiency that was characterized by a marked reduction in serum-γA and an absence of γA-containing cells in the spleen. However, essentially normal numbers of plasma cells were found in the gastrointestinal lamina propria of anti-γA-treated animals concomitantly with suppressed levels of γA in intestinal fluids.

THYMIC ALYMPHOPLASIA AND CONGENITAL ALEUKOCYTOSIS

PEDIATRICS ◽  
1964 ◽  
Vol 33 (2) ◽  
pp. 184-192
Author(s):  
David Gitlin ◽  
Gordon Vawter ◽  
John M. Craig
Keyword(s):  
Bone Marrow ◽  
Bacterial Infection ◽  
Plasma Cells ◽  
Normal Development ◽  
Lymphoid Tissues ◽  
Normal Numbers ◽  
Human Thymus

Thymic alymphoplasia has been found to be a part of the histopathological picture of congenital aleukocytosis. As in children with congenital agammaglobulinemia who have thymic alymphoplasia, the thymic anomaly is accompanied by lymphopenia and a marked generalized paucity of lymphocytes in the tissues or lymphocytic hypoplasia. The patient described in this report, a girl who succumbed at 15 days to overwhelming bacterial infection, also had agranulocytosis and no granulocytes or granulocyte precursors could be discerned in her bone marrow; megakaryocytes were present in the marrow in normal numbers and hematocytoblasts, normoblasts, and monocytes were present as well. Hence, the defect in this syndrome, whether intracellular or conveyed humorally, would appear to be highly selective. On the basis of the normal development of the human thymus and other lymphoid tissues including the bone marrow, it would seem that the defect in the development of the lymphocyte was manifest at or before the 10th week of gestation. The possible relations between lymphocytes, plasma cells, and granulocytes are discussed.

scholarly journals A splenic IgM memory subset with antibacterial specificities is sustained from persistent mucosal responses

2018 ◽  
Vol 215 (8) ◽  
pp. 2035-2053 ◽  
Author(s):  
Simon Le Gallou ◽  
Zhicheng Zhou ◽  
Lan-Huong Thai ◽  
Remi Fritzen ◽  
Alba Verge de los Aires ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Bacterial Infections ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Endogenous Retroviruses ◽  
Lymphoid Tissues ◽  
Gut Flora ◽  
Protective Capacity ◽  
B Cell Subsets

To what extent immune responses against the gut flora are compartmentalized within mucosal tissues in homeostatic conditions remains a much-debated issue. We describe here, based on an inducible AID fate-mapping mouse model, that systemic memory B cell subsets, including mainly IgM+ B cells in spleen, together with IgA+ plasma cells in spleen and bone marrow, are generated in mice in the absence of deliberate immunization. While the IgA component appears dependent on the gut flora, IgM memory B cells are still generated in germ-free mice, albeit to a reduced extent. Clonal relationships and renewal kinetics after anti-CD20 treatment reveal that this long-lasting splenic population is mainly sustained by output of B cell clones persisting in mucosal germinal centers. IgM-secreting hybridomas established from splenic IgM memory B cells showed reactivity against various bacterial isolates and endogenous retroviruses. Ongoing activation of B cells in gut-associated lymphoid tissues thus generates a diversified systemic compartment showing long-lasting clonal persistence and protective capacity against systemic bacterial infections.

LONG-COURSE ORAL CORTICOSTEROID TOXICITY IN CHILDREN

2016 ◽  
Vol 101 (9) ◽  
pp. e2.53-e2 ◽  
Author(s):  
Fahad Aljebab ◽  
Imti Choonara ◽  
Sharon Conroy
Keyword(s):  
Weight Gain ◽  
Growth Retardation ◽  
Oral Prednisolone ◽  
Incidence Rates ◽  
Cochrane Library ◽  
Varicella Zoster ◽  
Susceptibility To Infection ◽  
Oral Corticosteroids ◽  
Long Course ◽  
Increased Susceptibility

BackgroundLong courses of oral corticosteroids are commonly used in children in the management of conditions such as nephrotic syndrome, leukaemia, asthma and others. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels.MethodsA literature search of several databases; Embase, Medline, International Pharmaceutical Abstracts, CINAHL, the Cochrane Library and PubMed was performed to identify all studies where corticosteroids had been administered to paediatric patients ranging from 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to March 2014. All types of studies that provided clear information on ADRs were included.Results91 relevant studies were found from 27 countries. These studies represented a total of 6653 children and contained reports of 4124 ADRs, the majority in patients with leukaemia, haemangioma and asthma. Oral prednisolone was the most commonly prescribed corticosteroid (74% of patients). The three most frequent ADRs were weight gain, Cushingoid features and growth retardation. The incidence rates of patients with these three ADRs were 22.4%, 20.6% and 18.9%, respectively. Increased susceptibility to infection was the most serious ADR. 24 children died from infections, ten from varicella zoster and the others from different microorganisms.ConclusionsWeight gain, Cushingoid features and growth retardation were the most frequent ADRs seen when long-course oral corticosteroids were given to children. In addition, increased susceptibility to infection was the most common cause of mortality.

Defect in neutrophil killing and increased susceptibility to infection with nonpathogenic gram-positive bacteria in peptidoglycan recognition protein-S (PGRP-S)–deficient mice

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 689-697 ◽  
Author(s):  
Roman Dziarski ◽  
Kenneth A. Platt ◽  
Eva Gelius ◽  
Håkan Steiner ◽  
Dipika Gupta
Keyword(s):  
Inflammatory Responses ◽  
Protein S ◽  
Intracellular Killing ◽  
Gram Positive ◽  
Peptidoglycan Recognition Protein ◽  
Susceptibility To Infection ◽  
Gram Positive Bacteria ◽  
Recognition Protein ◽  
Factor Α ◽  
Increased Susceptibility

AbstractInsect peptidoglycan recognition protein-S (PGRP-S), a member of a family of innate immunity pattern recognition molecules conserved from insects to mammals, recognizes bacterial cell wall peptidoglycan and activates 2 antimicrobial defense systems, prophenoloxidase cascade and antimicrobial peptides through Toll receptor. We show that mouse PGRP-S is present in neutrophil tertiary granules and that PGRP-S–deficient (PGRP-S-/-) mice have increased susceptibility to intraperitoneal infection with gram-positive bacteria of low pathogenicity but not with more pathogenic gram-positive or gram-negative bacteria. PGRP-S-/- mice have normal inflammatory responses and production of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). Neutrophils from PGRP-S-/- mice have normal phagocytic uptake of bacteria but are defective in intracellular killing and digestion of relatively nonpathogenic gram-positive bacteria. Therefore, mammalian PGRP-S functions in intracellular killing of bacteria. Thus, only bacterial recognition by PGRP-S, but not its effector function, is conserved from insects to mammals.

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