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Chidiac G, Chrabieh R, Maamari M, El Khoury J, Ayoub N. Spontaneous complete resolution of alopecia totalis post SARS-CoV-2 infection. JAAD Case Rep 2022; 27:106-109. [PMID: 35937957 PMCID: PMC9347072 DOI: 10.1016/j.jdcr.2022.07.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
- Georgio Chidiac
- Faculty of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh, Lebanon.,Department of Dermatology, University Hospital Center-Notre Dame des Secours, Byblos, Lebanon
| | - Remie Chrabieh
- Department of Dermatology, Lebanese American University Medical Center-Rizk Hospital, Beirut, Lebanon
| | | | - Jinane El Khoury
- Department of Dermatology, Rose Marie and Gilbert Chaghoury School of Medicine, Lebanese American University, Beirut, Lebanon
| | - Nakhle Ayoub
- Faculty of Medicine and Medical Sciences, Holy Spirit University of Kaslik (USEK), Jounieh, Lebanon.,Department of Dermatology, French Hospital of the Levant, Beirut, Lebanon
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2
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Abdelhamid L, Luo XM. Diet and Hygiene in Modulating Autoimmunity During the Pandemic Era. Front Immunol 2022; 12:749774. [PMID: 35069526 PMCID: PMC8766844 DOI: 10.3389/fimmu.2021.749774] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 12/13/2021] [Indexed: 12/11/2022] Open
Abstract
The immune system is an efficiently toned machinery that discriminates between friends and foes for achieving both host defense and homeostasis. Deviation of immune recognition from foreign to self and/or long-lasting inflammatory responses results in the breakdown of tolerance. Meanwhile, educating the immune system and developing immunological memory are crucial for mounting defensive immune responses while protecting against autoimmunity. Still to elucidate is how diverse environmental factors could shape autoimmunity. The emergence of a world pandemic such as SARS-CoV-2 (COVID-19) not only threatens the more vulnerable individuals including those with autoimmune conditions but also promotes an unprecedented shift in people's dietary approaches while urging for extraordinary hygiene measures that likely contribute to the development or exacerbation of autoimmunity. Thus, there is an urgent need to understand how environmental factors modulate systemic autoimmunity to better mitigate the incidence and or severity of COVID-19 among the more vulnerable populations. Here, we discuss the effects of diet (macronutrients and micronutrients) and hygiene (the use of disinfectants) on autoimmunity with a focus on systemic lupus erythematosus.
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Affiliation(s)
- Leila Abdelhamid
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
- Department of Microbiology, College of Veterinary Medicine, Alexandria University, Alexandria, Egypt
| | - Xin M. Luo
- Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States
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3
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The magnitude of germinal center reactions is restricted by a fixed number of preexisting niches. Proc Natl Acad Sci U S A 2021; 118:2100576118. [PMID: 34301867 DOI: 10.1073/pnas.2100576118] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Antibody affinity maturation occurs in the germinal center (GC), a highly dynamic structure that arises upon antigen stimulation and recedes after infection is resolved. While the magnitude of the GC reaction is highly fluctuating and depends on antigens or pathological conditions, it is unclear whether GCs are assembled ad hoc in different locations or in preexisting niches within B cell follicles. We show that follicular dendritic cells (FDCs), the essential cellular components of the GC architecture, form a predetermined number of clusters. The total number of FDC clusters is the same on several different genetic backgrounds and is not altered by immunization or inflammatory conditions. In unimmunized and germ-free mice, a few FDC clusters contain GC B cells; in contrast, immunization or autoimmune milieu significantly increases the frequency of FDC clusters occupied by GC B cells. Excessive occupancy of GC niches by GC B cells after repeated immunizations or in autoimmune conditions suppresses subsequent antibody responses to new antigens. These data indicate that the magnitude of the GC reaction is restricted by a fixed number of permissive GC niches containing preassembled FDC clusters. This finding may help in the future design of vaccination strategies and in the modulation of antibody-mediated autoimmunity.
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4
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Ndawula C, Tabor AE. Cocktail Anti-Tick Vaccines: The Unforeseen Constraints and Approaches toward Enhanced Efficacies. Vaccines (Basel) 2020; 8:E457. [PMID: 32824962 PMCID: PMC7564958 DOI: 10.3390/vaccines8030457] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 08/12/2020] [Accepted: 08/13/2020] [Indexed: 12/17/2022] Open
Abstract
Ticks are second to mosquitoes as vectors of disease. Ticks affect livestock industries in Asia, Africa and Australia at ~$1.13 billion USD per annum. For instance, 80% of the global cattle population is at risk of infestation by the Rhipicephalus microplus species-complex, which in 2016 was estimated to cause $22-30 billion USD annual losses. Although the management of tick populations mainly relies on the application of acaricides, this raises concerns due to tick resistance and accumulation of chemical residues in milk, meat, and the environment. To counteract acaricide-resistant tick populations, immunological tick control is regarded among the most promising sustainable strategies. Indeed, immense efforts have been devoted toward identifying tick vaccine antigens. Until now, Bm86-based vaccines have been the most effective under field conditions, but they have shown mixed success worldwide. Currently, of the two Bm86 vaccines commercialized in the 1990s (GavacTM in Cuba and TickGARDPLUSTM in Australia), only GavacTM is available. There is thus growing consensus that combining antigens could broaden the protection range and enhance the efficacies of tick vaccines. Yet, the anticipated outcomes have not been achieved under field conditions. Therefore, this review demystifies the potential limitations and proposes ways of sustaining enhanced cocktail tick vaccine efficacy.
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Affiliation(s)
- Charles Ndawula
- Vaccinology Research program, National Livestock Resources Research Institute, P O. Box 5746, Nakyesasa 256, Uganda
| | - Ala E. Tabor
- Centre for Animal Science, Queensland Alliance for Agriculture & Food Innovation, The University of Queensland Australia, St Lucia 4072, Queensland, Australia
- School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia 4072, Queensland, Australia
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5
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Czaja AJ. Examining pathogenic concepts of autoimmune hepatitis for cues to future investigations and interventions. World J Gastroenterol 2019; 25:6579-6606. [PMID: 31832000 PMCID: PMC6906207 DOI: 10.3748/wjg.v25.i45.6579] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 11/25/2019] [Accepted: 11/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Multiple pathogenic mechanisms have been implicated in autoimmune hepatitis, but they have not fully explained susceptibility, triggering events, and maintenance or escalation of the disease. Furthermore, they have not identified a critical defect that can be targeted. The goals of this review are to examine the diverse pathogenic mechanisms that have been considered in autoimmune hepatitis, indicate investigational opportunities to validate their contribution, and suggest interventions that might evolve to modify their impact. English abstracts were identified in PubMed by multiple search terms. Full length articles were selected for review, and secondary and tertiary bibliographies were developed. Genetic and epigenetic factors can affect susceptibility by influencing the expression of immune regulatory genes. Thymic dysfunction, possibly related to deficient production of programmed cell death protein-1, can allow autoreactive T cells to escape deletion, and alterations in the intestinal microbiome may help overcome immune tolerance and affect gender bias. Environmental factors may trigger the disease or induce epigenetic changes in gene function. Molecular mimicry, epitope spread, bystander activation, neo-antigen production, lymphocytic polyspecificity, and disturbances in immune inhibitory mechanisms may maintain or escalate the disease. Interventions that modify epigenetic effects on gene expression, alter intestinal dysbiosis, eliminate deleterious environmental factors, and target critical pathogenic mechanisms are therapeutic possibilities that might reduce risk, individualize management, and improve outcome. In conclusion, diverse pathogenic mechanisms have been implicated in autoimmune hepatitis, and they may identify a critical factor or sequence that can be validated and used to direct future management and preventive strategies.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, United States
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6
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Metabolic pressure and the breach of immunological self-tolerance. Nat Immunol 2017; 18:1190-1196. [DOI: 10.1038/ni.3851] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 09/05/2017] [Indexed: 12/12/2022]
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7
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The hygiene hypothesis in autoimmunity: the role of pathogens and commensals. Nat Rev Immunol 2017; 18:105-120. [PMID: 29034905 DOI: 10.1038/nri.2017.111] [Citation(s) in RCA: 322] [Impact Index Per Article: 40.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The incidence of autoimmune diseases has been steadily rising. Concomitantly, the incidence of most infectious diseases has declined. This observation gave rise to the hygiene hypothesis, which postulates that a reduction in the frequency of infections contributes directly to the increase in the frequency of autoimmune and allergic diseases. This hypothesis is supported by robust epidemiological data, but the underlying mechanisms are unclear. Pathogens are known to be important, as autoimmune disease is prevented in various experimental models by infection with different bacteria, viruses and parasites. Gut commensal bacteria also play an important role: dysbiosis of the gut flora is observed in patients with autoimmune diseases, although the causal relationship with the occurrence of autoimmune diseases has not been established. Both pathogens and commensals act by stimulating immunoregulatory pathways. Here, I discuss the importance of innate immune receptors, in particular Toll-like receptors, in mediating the protective effect of pathogens and commensals on autoimmunity.
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8
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Zhang L, Ding Z, Heyman B. IgG3-antigen complexes are deposited on follicular dendritic cells in the presence of C1q and C3. Sci Rep 2017; 7:5400. [PMID: 28710441 PMCID: PMC5511153 DOI: 10.1038/s41598-017-05704-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 06/07/2017] [Indexed: 11/23/2022] Open
Abstract
IgG3, passively administered together with small proteins, induces enhanced primary humoral responses against these proteins. We previously found that, within 2 h of immunization, marginal zone (MZ) B cells capture IgG3-antigen complexes and transport them into splenic follicles and that this requires the presence of complement receptors 1 and 2. We have here investigated the localization of IgG3 anti-2, 4, 6-trinitrophenyl (TNP)/biotin-ovalbumin-TNP immune complexes in the follicles and the involvement of classical versus total complement activation in this process. The majority (50-90%) of antigen inside the follicles of mice immunized with IgG3-antigen complexes co-localized with the follicular dendritic cell (FDC) network. Capture of antigen by MZ B cells as well as antigen deposition on FDC was severely impaired in mice lacking C1q or C3, and lack of either C1q or C3 also impaired the ability of IgG3 to enhance antibody responses. Finally, IgG3 efficiently primed for a memory response against small proteins as well as against the large protein keyhole limpet hemocyanine.
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MESH Headings
- Adoptive Transfer
- Animals
- Antibodies, Monoclonal/genetics
- Antibodies, Monoclonal/metabolism
- Antigens/chemistry
- Antigens/immunology
- B-Lymphocytes/cytology
- B-Lymphocytes/immunology
- Biotin/chemistry
- Biotin/immunology
- Complement Activation
- Complement C1q/deficiency
- Complement C1q/genetics
- Complement C3/deficiency
- Complement C3/genetics
- Dendritic Cells, Follicular/cytology
- Dendritic Cells, Follicular/immunology
- Hemocyanins/chemistry
- Hemocyanins/immunology
- Hybridomas/immunology
- Immunization, Passive
- Immunoglobulin G/genetics
- Immunoglobulin G/metabolism
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Knockout
- Ovalbumin/chemistry
- Ovalbumin/immunology
- Picrates/chemistry
- Picrates/immunology
- Receptors, Complement/genetics
- Receptors, Complement/immunology
- Receptors, Complement 3d/genetics
- Receptors, Complement 3d/immunology
- Spleen/cytology
- Spleen/immunology
- Whole-Body Irradiation
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Affiliation(s)
- Lu Zhang
- Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, BMC, SE-751 23, Uppsala, Sweden
| | - Zhoujie Ding
- Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, BMC, SE-751 23, Uppsala, Sweden
| | - Birgitta Heyman
- Department of Medical Biochemistry and Microbiology, Uppsala University, Box 582, BMC, SE-751 23, Uppsala, Sweden.
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9
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Influenza bivalent vaccine comprising recombinant H3 hemagglutinin (HA) and H1 HA containing replaced H3 hemagglutinin transmembrane domain exhibited improved heterosubtypic protection immunity in mice. Vaccine 2015; 33:4035-40. [DOI: 10.1016/j.vaccine.2015.05.044] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Revised: 03/30/2015] [Accepted: 05/19/2015] [Indexed: 02/02/2023]
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10
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Ghazarian L, Diana J, Simoni Y, Beaudoin L, Lehuen A. Prevention or acceleration of type 1 diabetes by viruses. Cell Mol Life Sci 2013; 70:239-55. [PMID: 22766971 PMCID: PMC11113684 DOI: 10.1007/s00018-012-1042-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2011] [Revised: 05/22/2012] [Accepted: 05/24/2012] [Indexed: 12/31/2022]
Abstract
Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells. Even though extensive scientific research has yielded important insights into the immune mechanisms involved in pancreatic β-cell destruction, little is known about the events that trigger the autoimmune process. Recent epidemiological and experimental data suggest that environmental factors are involved in this process. In this review, we discuss the role of viruses as an environmental factor on the development of type 1 diabetes, and the immune mechanisms by which they can trigger or protect against this pathology.
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Affiliation(s)
- Liana Ghazarian
- Hôpital Saint Vincent de Paul/Cochin, Batiment Petit, 82 Avenue Denfert-Rochereau, 75014 Paris, France
| | - Julien Diana
- Hôpital Saint Vincent de Paul/Cochin, Batiment Petit, 82 Avenue Denfert-Rochereau, 75014 Paris, France
| | - Yannick Simoni
- Hôpital Saint Vincent de Paul/Cochin, Batiment Petit, 82 Avenue Denfert-Rochereau, 75014 Paris, France
| | - Lucie Beaudoin
- Hôpital Saint Vincent de Paul/Cochin, Batiment Petit, 82 Avenue Denfert-Rochereau, 75014 Paris, France
| | - Agnès Lehuen
- Hôpital Saint Vincent de Paul/Cochin, Batiment Petit, 82 Avenue Denfert-Rochereau, 75014 Paris, France
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11
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Folch H, Lopetegui F, Stegmeier E. Abrogation of antigenic competition phenomenon by a low dose of cyclophosphamide. ZENTRALBLATT FUR VETERINARMEDIZIN. REIHE B. JOURNAL OF VETERINARY MEDICINE. SERIES B 2010; 27:139-43. [PMID: 6451120 DOI: 10.1111/j.1439-0450.1980.tb01647.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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12
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Folch H, Eller G, Mena M, Esquivel P. Efecto supresor de altas dosis de Fitohemaglutinina en la respuesta inmune humoral y celular*. ACTA ACUST UNITED AC 2010. [DOI: 10.1111/j.1439-0450.1983.tb01835.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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13
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Disminución de las infecciones frente al ascenso de la alergia, autoinmunidad e inmunoinflamación. Med Clin (Barc) 2010; 134:513-4. [DOI: 10.1016/j.medcli.2009.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2009] [Accepted: 09/02/2009] [Indexed: 11/23/2022]
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14
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The suppression of immune system disorders by passive attrition. PLoS One 2010; 5:e9648. [PMID: 20300517 PMCID: PMC2838783 DOI: 10.1371/journal.pone.0009648] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2009] [Accepted: 02/02/2010] [Indexed: 01/22/2023] Open
Abstract
Exposure to infectious diseases has an unexpected benefit of inhibiting autoimmune diseases and allergies. This is one of many fundamental fitness tradeoffs associated with immune system architecture. The immune system attacks pathogens, but also may (inappropriately) attack the host. Exposure to pathogens can suppress the deleterious response, at the price of illness and the decay of immunity to previous diseases. This “hygiene hypothesis” has been associated with several possible underlying biological mechanisms. This study focuses on physiological constraints that lead to competition for survival between immune system cell types. Competition maintains a relatively constant total number of cells within each niche. The constraint implies that adding cells conferring new immunity requires loss (passive attrition) of some cells conferring previous immunities. We consider passive attrition as a mechanism to prevent the initial proliferation of autoreactive cells, thus preventing autoimmune disease. We see that this protection is a general property of homeostatic regulation and we look specifically at both the IL-15 and IL-7 regulated niches to make quantitative predictions using a mathematical model. This mathematical model yields insight into the dynamics of the “Hygiene Hypothesis,” and makes quantitative predictions for experiments testing the ability of passive attrition to suppress immune system disorders. The model also makes a prediction of an anti-correlation between prevalence of immune system disorders and passive attrition rates.
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15
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Lilliehöök B, Blomgren H. Influence of an M-locus difference on the cellular and humoral immunological reactivity against H-2 determined antigens of the mouse. Scand J Immunol 2008; 6:945-52. [PMID: 71757 DOI: 10.1111/j.1365-3083.1977.tb00415.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Studies were initiated to determine whether an immune response to the Mls antigen of C3H mice could modify responses of CBA lymphocytes (H-2-compatible) to a foreign H-2 complex. CBA lymphocytes, partially tolerant to the C3H-determined Mls antigen, generated less effector cell activity against C57Bl cells (H-2-incompatible) than lymph node cells from normal CBA donors when infused into irradiated C3H X C57Bl hosts. Effector cell activity was measured as the capacity of the cells in the irradiated spleens to inhibit CBA X C57Bl bone marrow proliferation. In contrast, immunization of CBA mice with C3H X C57Bl cells yielded lower antibody titers against C57Bl cells than immunization with CBA X C57Bl cells. Furthermore, preinjection of CBA mice with C3H X CBA cells strongly reduced the capacity of the animals to produce antibodies against C57Bl cells. Thus, these data support the conclusion that an immune response to a foreign Mls antigen may either enhance or suppress an immune response to H-2-incompatible cells.
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16
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Ismail M, Al-Ahaidib MS, Abdoon N, Abd-Elsalam MA. Preparation of a novel antivenom against Atractaspis and Walterinnesia venoms. Toxicon 2007; 49:8-18. [PMID: 17097125 DOI: 10.1016/j.toxicon.2006.08.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The two deadly snakes, Walterinnesia aegyptia (black desert cobra) and Atractaspis microlepidota (mole viper) share a common habitat in the central, eastern and western provinces of Saudi Arabia. Bites by either snake were characterized by rapid death, sometimes before reaching any medical facility. Confusing reports of "a black snake bite" are frequently found. The NAVPC had succeeded in preparing a highly effective antivenom against W. aegyptia venom which is now available in the market, but no antivenom against Atractaspis venom is found worldwide. This is probably because of the low molecular weight of sarafotoxins in the venom and hence their poor antigenic properties. At the NAVPC, sarafotoxins were separated by sequential gel filtration of A. microlepidota venom, while toxin T(III) of W. aegyptia venom obtained by cation exchange chromatography and gel filtration. Conjugation of the two toxins was carried out using glutaraldehyde in a two-step procedure followed by exhaustive dialysis. The conjugate was utilized to hyperimmunize 3-years old horses for 10 months, applying a low-dosage protocol and immunostimulants; the crude venoms of both snakes being added during the last 2 months. The F(ab')2 fraction of the antivenom was obtained by pH-guided salt precipitation, enzyme digestion and tangential desalting and filtration. The bivalent antivenom obtained protected mice and rats against the lethal effects of both venoms and rescued the rats challenged with lethal doses of the venoms in recovery experiments. It also neutralized the haemorrhagic, necrotizing and the cardiotoxic effects of A. microlepidota venom and the neuromuscular blocking effect of W. aegyptia venom. The antivenom offers a good rescue potential to those who are bitten by "a black snake" in Saudi Arabia.
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Affiliation(s)
- M Ismail
- 6 October University, Cairo, Egypt
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17
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Zhao Y, Benita Y, Lok M, Kuipers B, van der Ley P, Jiskoot W, Hennink WE, Crommelin DJA, Oosting RS. Multi-antigen immunization using IgG binding domain ZZ as carrier. Vaccine 2005; 23:5082-90. [PMID: 16029915 DOI: 10.1016/j.vaccine.2005.06.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2004] [Revised: 06/06/2005] [Accepted: 06/09/2005] [Indexed: 11/19/2022]
Abstract
This article describes a method in which multiple vaccine candidates can be tested in parallel for their immunogenicity. Antigens derived from the genome sequence of Neisseria meningitidis group B strain MC58 were cloned and expressed as recombinant proteins fused to the IgG-binding domain ZZ or to a His-tag. Immunization of mice with a mixture of 22 ZZ-fusion antigens applied with the adjuvant QuilA, induced an enhanced immune response as compared to the same antigen mixture without QuilA or a mixture containing the corresponding His-tagged antigens with QuilA. The enhanced immune response of the ZZ-fusion antigens/QuilA preparation was apparent from 1) the higher number of antigens in the mixture that elicited an antibody response and 2) the much lower antigen dose needed to get this response. Our approach using ZZ-fusion antigens/QuilA mixtures may serve as a high throughput discovery tool for new vaccine candidates.
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Affiliation(s)
- Yixian Zhao
- Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
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18
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Xu C, Wang S, Zhaoxia Z, Peng X. Immunogenic cross-reaction among outer membrane proteins of Gram-negative bacteria. Int Immunopharmacol 2005; 5:1151-63. [PMID: 15914320 DOI: 10.1016/j.intimp.2005.02.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2004] [Revised: 09/20/2004] [Accepted: 02/18/2005] [Indexed: 11/28/2022]
Abstract
In the present study, antigenic cross-reactivity of OMPs was investigated in several species of bacterial pathogens. Heterogeneous mouse or fish antisera were used to ascertain OMPs with cross-reactivity and cluster analysis was performed to analyze the distribution of cross-antigenic OMPs in diverse bacterial strains. We interestingly found that eleven and seven bands could be reacted with four kinds of heterogeneous mouse and fish antisera, respectively, and the phenograms constructed could provide ideal targeted bacteria for candidate genes of polyvalent vaccines. Importantly, there were significant differences in reaction with bacteria between mouse and fish antisera, but commonly antigenic bands still existed between them. Our results suggest that the cross-reactivity of OMPs exists commonly in Gram-negative bacteria, which may be a promising choice for the development of polyvalent OMP vaccines. Meanwhile, cluster analysis will help to understand the relation of cross-antigenic OMPs among Gram-negative bacteria.
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Affiliation(s)
- Changxin Xu
- Department of Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, P.R. China
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19
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Randi G, Altieri A, Chatenoud L, Chiaffarino F, La Vecchia C. Infections and atopy: an exploratory study for a meta-analysis of the "hygiene hypothesis". Rev Epidemiol Sante Publique 2005; 52:565-74. [PMID: 15741918 DOI: 10.1016/s0398-7620(04)99095-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
BACKGROUND According to the "hygiene hypothesis" selected allergic diseases could be prevented by exposure to infectious agents during early childhood. METHODS This study was performed to assess the feasibility of a future meta-analysis on the "hygiene hypothesis" and atopic diseases. Differences concerning the potential association with a history of infectious events, in terms of magnitude and homogeneity of global risk estimates between the three major atopic diseases (i.e. atopic dermatitis, asthma and allergic rhinitis) were examined. We conducted a preliminary analysis on a sample of articles published on this topic and cited in a recent and authoritative review. RESULTS The ranges of relative risks estimates (between 0.6 and 0.8) were similar for atopic dermatitis, allergic rhinitis and asthma. Compared with asthma and allergic rhinitis, reported global risk estimates were more stable for atopic dermatitis (lowest heterogeneity). Our analysis suggests that three main categories of indirect markers of exposure to infection can be identified: 1) geographical gradient, 2) indices of potential contact with infectious agents (such as number of siblings) and 3) history of infectious events. CONCLUSIONS In this exploratory study, we chose articles cited in a single review and obtained a preliminary quantification of the association between infections and atopic diseases. The association with indirect markers of infection corresponded to 20% protection for atopic dermatitis, 30% for allergic rhinitis and 40% for asthma. In a subsequent meta-analysis, diseases should be considered separately and differences between types of exposures should be taken into account as one of the major end-points, with attention to time since exposure and disease onset.
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Affiliation(s)
- G Randi
- Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, I-20157 Milano, Italia
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20
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21
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Affiliation(s)
- Jean-Francois Bach
- INSERM Unité 25, Institut de Recherches Necker-Enfants Malades, Hôpital Necker, Paris, France.
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Gough L, Sewell HF, Shakib F. The proteolytic activity of the major dust mite allergen Der p 1 enhances the IgE antibody response to a bystander antigen. Clin Exp Allergy 2001; 31:1594-8. [PMID: 11678860 DOI: 10.1046/j.1365-2222.2001.01207.x] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND We have recently demonstrated that immunization of mice with proteolytically active Der p 1, the major dust mite allergen, results in a significant enhancement in total and Der p 1-specific IgE synthesis compared to mice immunized with Der p 1 that has been irreversibly blocked with the cysteine protease inhibitors E-64 and iodoacetamide. Thus, the demonstration that the proteolytic activity of Der p 1 enhances total IgE production, apart from increasing Der p 1-specific IgE, suggests that this allergen may have an IgE-specific adjuvant effect. OBJECTIVE To determine if the proteolytic activity of Der p 1 has an IgE-specific adjuvant effect. METHODS We have examined this concept in experiments whereby ovalbumin, used as a bystander antigen, was injected alone or coinjected with either proteolytically active or inactive Der p 1 into groups of mice and IgE and IgG antibody responses were measured. RESULTS Here we demonstrate for the first time that the proteolytic activity of Der p 1, when given at 10-fold higher concentration, enhances the IgE antibody response to ovalbumin. CONCLUSIONS These findings show that the proteolytic activity of Der p 1 leads to the augmentation of IgE antibody responses to itself and to other allergens present in the microenvironment.
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Affiliation(s)
- L Gough
- Division of Molecular and Clinical Immunology, Faculty of Medicine and Health Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK
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23
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Abstract
Infectious agents may induce autoimmune disease through several mechanisms, notably antigen mimicry and inflammation of the target organ; conversely, infections may protect from autoimmune diseases. This paradoxical effect has been demonstrated for a number of bacteria, viruses and parasites on a variety of spontaneous or experimentally induced animal models of autoimmune diseases (e.g. experimental allergic encephalomyelitis, lupus mice, non-obese diabetic mice). The mechanisms of the protection are still ill-defined, and probably vary according to models. Stimulation of immunoregulatory CD4 T cells has been shown to play a central role in several major models. The role of superantigens is also important, like that of Toll-like receptors. Antigen competition is another major mechanism, itself open to several interpretations. Epidemiological data support a protective role of infections on human allergic and autoimmune diseases. These diseases are much more common in countries with high socio-economic development (typically Northern countries in Europe). The reason for this cannot be fully explained by genetic differences because migrating populations develop these diseases with the same incidence of the adoptive country rather than that of the country of origin. It is interesting that the frequency of these diseases has been increasing in developed countries over the last 20 years but not in undeveloped ones.
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Affiliation(s)
- J F Bach
- INSERM U 25, Hôpital Necker, Paris, France.
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24
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Caulfield MJ, Smith JG, Wang S, Capen RC, Blondeau C, Lentsch S, Arminjon F, Sabouraud A. Immunogenicity of a hexavalent combination vaccine in rhesus monkeys. Vaccine 2000; 19:902-7. [PMID: 11115714 DOI: 10.1016/s0264-410x(00)00299-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Preclinical immunogenicity studies were conducted in rhesus monkeys to determine whether there is immune interference in the response to one or more components of a hexavalent vaccine (Hexavac) that contains antigens from Haemophilus influenzae (Hib), hepatitis B (HB), diphtheria (D), tetanus (T), acellular pertussis (aP) and inactivated polio virus (IPV). Antibody responses were measured following co-administration of the components at three separate anatomical sites or administration as a hexavalent combination in a single site. After three injections of the hexavalent vaccine, the peak antibody responses to each component of the vaccine were >100-fold above pre-immune titers and persisted at levels >10-fold above pre-immune titers at approximately 1 year. Immune interference was observed in the peak response to HB, D and pertussis toxin, but was not seen at later time points. The results indicate that the rhesus monkey model may be useful for pre-clinical evaluation of combination vaccines.
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Affiliation(s)
- M J Caulfield
- Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA 19486, USA.
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25
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Colmenero P, Liljeström P, Jondal M. Induction of P815 tumor immunity by recombinant Semliki Forest virus expressing the P1A gene. Gene Ther 1999; 6:1728-33. [PMID: 10516722 DOI: 10.1038/sj.gt.3301004] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The methylcholantrene-induced P815 mastocytoma tumor is derived from DBA/2 mice and expresses a weak tumor rejection antigen, P815A. The P1A gene, which encodes for the P815A antigen, is silent in most normal tissues with the exception of testis and placenta. These characteristics make P815 an interesting mouse model for the human MAGE-type tumor antigens. Recombinant Semliki Forest virus particles (rSFV) were constructed that expressed variants of the P815 antigen. Such particles, when used for vaccination, express the antigen only transiently since the viral vector is incapable of productive replication. Nevertheless, mice vaccinated with rSFV generated strong CTL responses and were protected against P815 tumor challenge.
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Affiliation(s)
- P Colmenero
- Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden
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26
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Dearman RJ, Hope JC, Hopkins SJ, Kimber I. Antigen-induced unresponsiveness in contact sensitivity: association of depressed T lymphocyte proliferative responses with decreased interleukin 6 secretion. Immunol Lett 1996; 50:29-34. [PMID: 8793556 DOI: 10.1016/0165-2478(96)02512-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Topical exposure of mice to the contact allergen oxazolone induces both 4 persistent antigen-specific down-regulation of subsequent lymph node cell (LNC) proliferative responses stimulated by the same chemical and a more transient depression of LNC proliferative responses provoked by exposure to unrelated chemical sensitizers: the latter being associated with antigenic competition in contact sensitivity. In this paper a relationship between reduced LNC proliferative activity and the secretion of interleukin 6 (IL-6) is described. Pretreatment of mice with oxazolone caused a persistent, dose-dependent inhibition of LNC proliferative activity and a parallel reduction of IL-6 secretion when mice were re-exposed, at a different site, to the same chemical. Consistent with dendritic cells (DC) being the major source of IL-6 within allergen-activated lymph nodes, depletion of Thy-lt T lymphocytes did not compromise production of this cytokine. Although in mice pretreated with oxazolone IL-6 secretion by cultured LNC was impaired markedly, the initial IL-6 content of freshly isolated LNC was apparently normal. These data suggest that the down-regulation of lymphocyte proliferative responses induced by exposure of mice to oxazolone, and the consequential impaired responsiveness, is associated with, and possibly secondary to, the reduced secretion by lymph node DC of IL-6, a cytokine that is a costimulator of T lymphocyte activation and the production of which correlates closely with the vigour of LNC proliferative activity.
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Affiliation(s)
- R J Dearman
- Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK
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27
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Hunt JD, Jackson DC, Wood PR, Stewart DJ, Brown LE. Immunological parameters associated with antigenic competition in a multivalent footrot vaccine. Vaccine 1995; 13:1649-57. [PMID: 8719515 DOI: 10.1016/0264-410x(95)00145-q] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
A murine model for antigenic competition with multivalent D. nodosus pili vaccine has been established that parallels the phenomenon observed in sheep where levels of antibody, specific for any particular serogroup of pili, are significantly lower following vaccination in the presence of multiple serogroups of pili than with that serogroup alone. This competition was observed in both high and low responder strains of mice and was not dependent on the multiplicity of the antigens in the multivalent vaccine but could be observed with a large excess of a single heterologous serogroup. Competition was manifest by a reduction in the number of serogroup-specific antibody secreting cells elicited in response to vaccination. The antibody response to a single serogroup of pili reached a plateau at high doses and it was at these doses that antigenic competition was most pronounced, under conditions where both B- and T-cell responses were limiting. The limit in T-cell responsiveness was not imposed at the level of presentation of antigen. Pili-specific T cells were largely cross-reactive for different serogroups, and under conditions of limiting T-cell stimulation within a lymph node the available T cells would have to be shared between B cells specific for each serogroup of pili, which may in turn result in the decrease of serogroup-specific antibody induced following inoculation with the multivalent vaccine.
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MESH Headings
- Animals
- Antibodies, Bacterial/biosynthesis
- Antibody-Producing Cells/immunology
- Antigen-Presenting Cells/immunology
- Antigens, Bacterial/chemistry
- Antigens, Bacterial/immunology
- Antigens, Bacterial/pharmacology
- Bacterial Vaccines/immunology
- Binding, Competitive/immunology
- Dose-Response Relationship, Immunologic
- Female
- Fimbriae, Bacterial/immunology
- Foot Rot/immunology
- Histocompatibility Antigens Class II/chemistry
- Immunoglobulin Isotypes/biosynthesis
- Lymphocyte Activation
- Lymphocyte Count
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Mice, Inbred CBA
- Mice, Nude
- T-Lymphocytes/immunology
- Vaccines, Synthetic/immunology
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Affiliation(s)
- J D Hunt
- Department of Microbiology, University of Melbourne, Parkville, Victoria, Australia
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28
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Bernstein JM, Rich GA, Odziemiec C, Ballow M. Are thymus-derived lymphocytes (T cells) defective in the nasopharyngeal and palatine tonsils of children? Otolaryngol Head Neck Surg 1993; 109:693-700. [PMID: 8233506 DOI: 10.1177/019459989310900410] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
The present study was conducted to evaluate the response of adenoidal T cells and B cells in the production of immunoglobulins. There appears to be a consistent inability of adenoidal T cells to turn on B cells to mature into immunoglobulin-secreting plasma cells. This phenomenon did not appear to be due to suppressor activity of adenoidal T cells because T cells from other sources appeared to effectively result in adenoidal B cell maturation, even in the presence of adenoidal T cells. Both tonsils and adenoids appear to have defective IL-2 production, in response to both mitogens and specific antigens. It is hypothesized that a cytokine(s) may be released in adenoids that downregulate IL-2 production and result in immune suppression in the adenoids of children with recurrent otitis media and chronic sinusitis.
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Affiliation(s)
- J M Bernstein
- Department of Otolaryngology, State University of New York at Buffalo
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29
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Janssen M, Freyvogel TA, Meier J. Antigenic relationship between the venom of the night adder Causus maculatus and venoms of other viperids. Toxicon 1990; 28:975-83. [PMID: 1706897 DOI: 10.1016/0041-0101(90)90026-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Monovalent antivenoms were raised in mice against the venoms of Causus maculatus, Vipera ammodytes, Echis carinatus, Cerastes cerastes, Bitis arietans, Agkistrodon rhodostoma and Bothrops atrox. These antivenoms as well as four commercially available antivenoms were tested against the venoms of 15 viperid species by means of immunoelectrophoresis and/or ELISA. Cross-reactive protein bands were determined by immunoblot. ELISA cross-reactions of C. maculatus antivenom were low with all heterologous venoms. When investigating the other viperine antivenoms in ELISA stronger cross-reactions were observed with several heterologous venoms. In immunoblot, two heterologous antivenoms cross-reacted with one or two protein bands of C. maculatus venom whereas there were at least four heterologous antivenoms cross-reacting with each of the other venoms. The findings indicate that there is little antigenic affinity between C. maculatus venom and the other venoms investigated. Broad in vitro cross-reactions between viperine antivenoms and Causus venom which were reported in literature seem to be attributable to the use of antivenoms of commercial grade. Specificity of commercially produced, mono- or polyvalent antivenoms may not be strictly limited to those venoms, against which potency is claimed on the label of the product.
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30
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Ruiz BH, Carvajal RE, Ortiz-Ortiz L. Modifications of the immune response induced by Histoplasma capsulatum products. Mycopathologia 1990; 109:1-9. [PMID: 2183061 DOI: 10.1007/bf00436999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
To understand the host-parasite relationship in histoplasmosis, mice were inoculated with histoplasmin (HP), the filtrate of aged cultures of Histoplasma capsulatum, and the immune response of these mice towards sheep red blood cells (SRBC) and to trinitrophenyl hapten was studied. The filtrate abrogated completely the primary antibody response to both antigens as measured by the number of spleen hemolytic plaque forming cells when HP was administered at doses greater than 200 micrograms two days before the antigen. Suppression was elicited by HP when it was injected either intravenously, intraperitoneally, or subcutaneously. Inoculation with HP and antigen on the same day did not result in suppression. The secondary antibody response was not modified at any dose. Variation of the response with time was determined by counting the number of rosette forming cells (RFC) to SRBC every two days for a total of 21 days. Antibody-mediated RFC ('B' rosettes) were depressed throughout the experiment, while the number of non 'B', presumably T, RFC did not vary from control values. In animals inoculated with HP alone, high number of RFC were detected on day 11 after HP inoculation, suggesting that HP may have polyclonal activation effects. These results support the possibility that H. capsulatum evades the immune defenses by induction of a suppressive phenomenon in which the afferent limb of the immune response is not involved. This effect appeared to be induced directly by a product of the fungus, instead of by factors generated during the immune response to this microorganism.
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Affiliation(s)
- B H Ruiz
- Instituto de Investigaciones Biomédicas, Facultad de Medicina, Universidad Nacional Autónoma de México
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31
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Gill HS, Charleston WA, Moriarty KM. Immunosuppression in Sarcocystis muris-infected mice: evidence for suppression of antibody and cell-mediated responses to a heterologous antigen. Immunol Cell Biol 1988; 66 ( Pt 3):209-14. [PMID: 2485090 DOI: 10.1038/icb.1988.26] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Mice infected with Sarcocystis muris showed a significant reduction in plaque-forming cells (PFC) and delayed-type hypersensitivity (DHS) responses to an unrelated protein antigen, bovine gamma-globulin, when compared with uninfected controls. This immunosuppression was observed only when infection preceded immunization or when mice were immunized concurrently with infection, suggesting that suppression induced by murine sarcocystosis affected the induction and/or the differentiation of antigen-sensitive immunocytes. The immunosuppression lasted for 5 weeks, the period of this study, and affected cell-mediated responses more than antibody responses. The secondary PFC and DHS responses of mice immunized 14 days after infection and re-immunized 21 days later were also significantly lower than those of uninfected controls, whereas the secondary PFC and DHS responses of mice primed before infection were unimpaired. This indicated that S. muris infection affects only the induction but not the expression of immune memory.
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Affiliation(s)
- H S Gill
- Department of Veterinary Pathology and Public Health, Massey University, Palmerston North, New Zealand
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32
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Beuvery EC, van Delft RW, Miedema F, Kanhai V, Nagel J. Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice. Infect Immun 1983; 41:609-17. [PMID: 6409811 PMCID: PMC264686 DOI: 10.1128/iai.41.2.609-617.1983] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component. Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules. In this study, the influence of these characteristics on the antibody response to both components in mice was investigated. The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied. Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced. These characteristics favor the application of this conjugate as a vaccine for human use.
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33
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Azar Y, Ben-Sasson SZ. In vivo helper activity of enriched populations of antigen-specific T lymphocytes. Cell Immunol 1983; 79:150-6. [PMID: 6190579 DOI: 10.1016/0008-8749(83)90057-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Enrichment of murine antigen-specific T cells was achieved by stimulation of primed lymph node cells with macrophages containing the immunizing antigen. After a week in culture, the in vitro-sensitized lymphocytes had an increased helper activity. Inoculation of 10(7) egg albumin (OVA)-enriched T cells together with hapten coupled to OVA, elevated the number of splenic antihapten-producing cells of primed or unprimed mice. Augmentation of the hapten specific B-cell response could be observed as early as 4 days following the injection of the enriched population and peaked at Day 7. The enhancing effect of the enriched population of antigen-specific T cells was carrier specific since it occurred only in the presence of hapten coupled to the T-cell sensitizer [2,4-dinitrophenol (DNP)-OVA]. When given with the hapten conjugated to an irrelevant carrier [DNP-human gamma globulin (HGG)], the enriched lymphocytes caused a depression in the anti-DNP response. The capacity of in vitro enriched lymphocytes to promote a substantial antigen-specific helper activity (up to 1 anti-DNP producing cell per 10(3) spleen cells) upon adoptive transfer to nonirradiated mice, provides an experimental system for studying B-T collaboration in vivo under the normal physiological conditions.
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34
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Hagan P, Wakelin D. Nematospiroides dubius: effect of infect on lymphocyte responses to Trichinella spiralis in mice. Exp Parasitol 1982; 54:157-65. [PMID: 7128714 DOI: 10.1016/0014-4894(82)90122-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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35
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Pérez H, Pocino M, Malavé I. Nonspecific immunodepression and protective immunity in mice infected with Leishmania mexicana. Infect Immun 1981; 32:415-9. [PMID: 7019070 PMCID: PMC351458 DOI: 10.1128/iai.32.2.415-419.1981] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
C57BL/6 mice infected with Leishmania mexicana showed depression of the in vitro immunoglobulin M-plaque-forming cell response to sheep erythrocytes. Immunodepression was present 3 weeks after inoculation and was maximal at 11 weeks. Thereafter, there was a gradual return to normal immunoresponsiveness correlated with the resolution of lesions. At the time of maximal immunodepression, spleen cells from infected mice diminished the plaque-forming cell response to sheep erythrocytes of normal spleen cells. On the other hand, specific responses, as exemplified by protective immunity to a challenge infection and delayed hypersensitivity responses to parasite antigens, were apparently unaffected. These responses were both present in mice bearing primary lesions and were maximal in recovered mice. The significance of these findings is discussed in relation to a current hypothesis on parasite-induced immunodepression.
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36
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Monoclonal antibody analysis of complex biological systems. Combination of cell hybridization and immunoadsorbents in a novel cascade procedure and its application to the macrophage cell surface. J Biol Chem 1981. [DOI: 10.1016/s0021-9258(19)69532-3] [Citation(s) in RCA: 67] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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37
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Abstract
Immunological rejection has been the major problem limiting the successful transplantation of tissue from one animal to another. Recent technological developments, combined with the use of the central nervous system as an immunologically privileged site, suggest that it might be possible to achieve long-term survival of hormone-secreting tissues, between two gentically dissimilar animals, if these tissues are transplanted to the brain and subarachnoid space of the host. The physiological parameters that should be considered in the clinical application of a transplant of this type are discussed.
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38
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Johnson LL, Bailey DW, Mobraaten LE. Antigenic competition between minor (non-H-2) histocompatibility antigens. Immunogenetics 1981; 13:451-5. [PMID: 7028606 DOI: 10.1007/bf00346026] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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39
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Johnson LL, Bailey DW, Mobraaten LE. Genetics of histocompatibility in mice. II. Survey for interactions between minor (non-H-2) antigens by skin grafting. Immunogenetics 1980; 11:363-72. [PMID: 7000698 DOI: 10.1007/bf01567803] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Twenty-five congenic mouse strains differing at distinguishable minor (non-H-2) histocompatibility loci were paired in 71 different combinations. F1 offspring were used as skin-graft donors for more than 4000 recipients to test whether immune responses to parental strain antigens were statistically independent. Thirty-four (48 percent) of the 71 combinations were predicted adequately by an independent response hypothesis. A simple additive model was consistent with 39 (55 percent) of the observed responses, although 18 of these were among those in agreement with the independent hypothesis. A synergistic response faster than that predicted by either the independent or additive response model was seen in 12 (17 percent) of the combinations. The remaining 5 percent were not well described by any of these models. No strain was represented with unusual frequency among those involved in synergistic interactions.
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40
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Abstract
A/SN mice infected with N. Brasiliensis showed depressed anti-DNP antibody responses following immunization with DNP-Asc in alum. The immunosuppression was only observed when infection preceded immunization by between 2 and 7 days, and was not achieved when the interval was extended to 10 days. The suppression lasted at least 50 days, and affected IgE levels more than IgG1 or IgG agglutinating anti-DNP antibodies. A high dose of infective larvae (500-1000 per mouse) was necessary to induce suppression. Use of low dose irradiation indicated a parasite-induced radiosensitive component of the mouse immune system which negatively regulated the anti-DNP IgE response. These results suggested that the parasite could induce suppression in an analogous manner to sequential antigen-induced suppression (AIS).
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41
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Correa M, Miller HC, Esselman WJ. Antigen induced modulation by shed lymphocyte membrane gangliosides. IMMUNOLOGICAL COMMUNICATIONS 1980; 9:543-57. [PMID: 6159304 DOI: 10.3109/08820138009052994] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
A unique regulatory mechanism has been proposed for ganglioside which functions to immune responses to temporarily restrain B lymphocytes of all specificities and at various levels of differentiation. Utilizing antigen competition protocols, experiments was designed to exploit and extend the antigen induction properties of this modulation. Spleen cell cultures were prepared from TNP-BGG primed mice. In vitro stimulation of the cultures with ovalbumin (OVA) followed 24 hours later by addition of TNP-BGG resulted in only one weak TNP hemolytic plaque responses when compared to control cultures which did not receive OVA. OVA induced competitive effects were absorbed by anti-Thy-1 or anti-ganglioside. Glycolipids could be extracted from the culture media supernatants of experimental and control groups as a ganglioside fraction containing Thy-1 determinants. These molecules, when formulated into liposomes, produced the same modulatory effect as that of media from the competitive culture group. These results support and extend the proposal that glycolipids released by antigen stimulated T cells provide unrestricted modulation of B cells to prevent overload during T cell maturation. This regulatory mechanism prevents direct antigen binding and prepares B cell receptivity for further stimuli which orchestrate their terminal differentiation into plasma cells.
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42
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Pierce CW, Tadakuma T, Kapp JA. Role of nonspecific and specific suppressor factors in immunity. Ann N Y Acad Sci 1979; 332:336-44. [PMID: 93866 DOI: 10.1111/j.1749-6632.1979.tb47127.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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43
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Komatsu T, Nishimura T, Sano R, Shinka S. Ascaris suum: suppression of reaginic and hemagglutinating antibody responses in the mouse by crude extract and maintenance fluid. Exp Parasitol 1979; 47:158-68. [PMID: 437015 DOI: 10.1016/0014-4894(79)90069-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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44
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Nemirovsky MS. Effects of antigenic competition between sperm autoantigens and ovalbumin upon humoral and cell-mediated immunity and the development of autoimmune aspermatogenic orchitis (AIAO) in guinea pigs. ARCHIVES OF ANDROLOGY 1979; 3:43-9. [PMID: 485659 DOI: 10.3109/01485017908985047] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The effects of antigenic competition between ovalbumin and sperm autoantigens have been studied in guinea pigs. There was an inhibition of antiovalbumin antibody production up to 60 days after immunization. The cell-mediated immunity against ovalbumin was also depressed at day 30. The simultaneous immunization with both antigens has no effect upon the humoral and cell-mediated immunity against spermatozoa. During the period of inhibition of the humoral and cell-mediated antiovalbumin response, the number of animals developing autoimmune aspermatogenic orchitis was diminished compared to those immunized with spermatozoa alone. Later on, there was no difference between the two groups. The transient inhibition of the immune response against ovalbumin can be explained by the particulate nature of the autoantigens. The sperm cells may be easily trapped by the dendritic reticular cells of the draining lymph nodes. This in turn could affect T cell recognition at early stages, orienting it predominantly toward the sperm autoantigens. At day 90 the situation returned to that present in animals immunized with ovalbumin alone.
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45
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Yong WK, Heath DD, Parmeter SN. Echinococcus granulosus, Taenia hydatigena, T. ovis: evaluation of cyst fluids as antigen for serodiagnosis of larval cestodes in sheep. N Z Vet J 1978; 26:231-4. [PMID: 281662 DOI: 10.1080/00480169.1978.34550] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Taniguchi T, Nomoto K, Miake S, Takeya K. Proliferation of hemolysin-plaque-forming cells in nude mice and normal littermates subjected to antigenic competition. Microbiol Immunol 1978; 22:205-14. [PMID: 357933 DOI: 10.1111/j.1348-0421.1978.tb00364.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The increase of PFC per spleen and the development of hemolytic foci were examined to clarify the patterns of clonal expansion of B-lymphocytes in athymic nude mice (nu/nu) and normal littermates (nu/+) subjected to the procedure for antigenic competition between horse erythrocytes (HRBC) and sheep erythrocytes (SRBC). In normal littermates without pretreatment with HRBC, a small number of PFC and hemolytic foci of small size were detected 2-days after the challenge with SRBC. The number of PFC increased progressively from day 2 to day 4, and hemolytic foci increased in the number and size during the period. In nude mice, a small number of PVFC were detected on day 2 and the number increased only slightly from day 2 to day 4. No large hemolytic foci were detected during the period. In normal littermates subjected to the procedure for antigenic competition, the patterns of increase of PFC and development of hemolytic foci were similar to those in nude mice. In nude mice, the procedure for antigenic competition exerted almost no effect on the patterns.
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Drucker M, Drucker I, Neter E, Bernstein J, Ogra PL. Cell mediated immune responses to bacterial antigens on human mucosal surfaces. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 1978; 107:479-88. [PMID: 311141 DOI: 10.1007/978-1-4684-3369-2_54] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Bro-Jørgensen K. The interplay between lymphocytic choriomeningitis virus, immune function, and hemopoiesis in mice. Adv Virus Res 1978; 22:327-69. [PMID: 345777 DOI: 10.1016/s0065-3527(08)60777-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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