{"title":"Immunoglobulin gene usage in the human anti-pathogen response.","authors":"M M Newkirk, J D Rioux","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 3","pages":"153-60"},"PeriodicalIF":0.0,"publicationDate":"1995-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19530234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospects for use of recombinant BPI in the treatment of gram-negative bacterial infections.","authors":"P Elsbach, J Weiss","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The bactericidal/permeability-increasing protein (BPI), a potent cytotoxin specific for Gram-negative bacteria and an endotoxin-neutralizing agent, is a major component of the antimicrobial arsenal of mammalian polymorphonuclear leukocytes. The antibacterial and endotoxin-neutralizing activities of the N-terminal portion (approximately 25 kDa) of BPI are at least equal to those of the holoprotein (approximately 50 kDa). Recombinant N-terminal fragments of BPI are antibacterial and inhibit host cell responses to endotoxin in whole blood ex vivo and in animal experiments. BPI administered to both animals and man is apparently nontoxic and nonimmunogenic and acts synergistically with some antibiotics. Thus, the prospects for the therapeutic use of bioactive BPI fragments in serious Gram-negative bacterial infections are highly encouraging.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 2","pages":"102-9"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18618603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The simian herpesviruses.","authors":"R Eberle, J Hilliard","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Increased use of monkeys in biomedical research has led to an intensified awareness of potential dangers posed by zoonotic infections. Zoonoses have an impact not only upon human health and safety but also upon continued availability of nonhuman primate resources for the biomedical community. Neurotropic herpesviruses indigenous to primates are significant owing to their potential for causing severe or fatal infections when transmitted between human and nonhuman primates or between different species of monkeys. Although the macaque herpesvirus (B virus) is known to many investigators, other simian herpesviruses have remained relatively obscure in spite of reports of disease-causing potential. In this review we summarize what is known about the natural history and pathogenic potential of simian alpha-herpesviruses. Recent research into the molecular biology of this group of viruses is also reviewed, and recent advances toward development of diagnostic tests based on these data are discussed.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 2","pages":"55-70"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18618607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trial objectives and end points for measuring the efficacy of HIV vaccines.","authors":"R Hoff, L F Barker","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In order to prove the efficacy of human immunodeficiency virus (HIV) vaccines, it will be necessary to do large-scale trials in populations at high risk of acquiring HIV infection. The choice of objectives and end points and their measurement will be key to the design of efficacy trials. To address these issues, the National Institute of Allergy and Infectious Diseases convened several workshops and discussions at national meetings. These discussions have concluded that many factors will contribute to the selection of practical primary objectives and end points for efficacy trials of HIV vaccines. For initial trials the objective of preventing the establishment of chronic infection is a reasonable choice, given the current state of knowledge. However, given the complexities of HIV and the acquired immunodeficiency syndrome, it will be important to collect data and evaluate other potential objectives and end points as well.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 2","pages":"95-101"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18619124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Training in infectious disease: planning for the future.","authors":"M S Klempner, L O Langdon","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 2","pages":"110-4"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18618604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Wasting syndrome in AIDS: pathophysiologic mechanisms and therapeutic approaches.","authors":"S E Weinroth, D M Parenti, G L Simon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Wasting syndrome is a common complication of HIV infection and is marked by progressive weight loss and weakness, often associated with fever and diarrhea. The pathophysiologic mechanisms responsible for this syndrome are not well defined, but it is clear that this is a multifactorial process in which the relative contribution of individual etiologic factors vary among patients. Considerations include inadequate diet, malabsorptive phenomena, metabolic derangements, and cytokine activity. The onset of opportunistic infections is often accompanied by a hypermetabolic state characterized by progressive weight loss. Potential cytokines that may promote weight loss in AIDS patients include tumor necrosis factor, interleukin-1, interleukin-6, and alpha-interferon. At present there is no effective treatment. Multiple therapeutic methods, including enteral and parenteral alimentation, appetite stimulants, recombinant growth hormone, and cytokine modulators, are currently being explored.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 2","pages":"76-94"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18618610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P J Hotez, J M Hawdon, M Cappello, B F Jones, D I Pritchard
{"title":"Molecular pathobiology of hookworm infection.","authors":"P J Hotez, J M Hawdon, M Cappello, B F Jones, D I Pritchard","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Within the past 2 years, progress has been made in the identification, isolation, and cDNA cloning of several macromolecules from hookworms. While the predicted amino acid sequences of some cDNAs resemble those from other nematodes, such as Caenorhabditis elegans, other cDNAs are unique to hookworms. Studies are under way to evaluate the function of these recombinant hookworm polypeptides with respect to the biology of hookworms in experimental animal models. The recombinant polypeptides are also under evaluation as vaccine targets and as natural products used in the treatment of human cardiovascular and autoimmune diseases.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 2","pages":"71-5"},"PeriodicalIF":0.0,"publicationDate":"1995-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18618609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vibrio cholerae O139 Bengal: emergence of a new epidemic strain of cholera.","authors":"J G Morris","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In October 1992, a new strain of cholera, subsequently designated Vibrio cholerae O139 Bengal, was detected in Madras, India. This strain spread rapidly through the Indian subcontinent and has now been reported in many parts of Asia, with additional cases identified in travelers to North American and the Middle East. Phylogenetically, V. cholerae O139 Bengal is very closely related to \"standard\" V. cholerae O1 El Tor strains; it produces cholera toxin and causes an illness identical that seen with V. cholerae O1. However, prior immunity to V. cholerae O1 El Tor does not appear to protect against illness caused by V. cholerae O139 Bengal. O139 Bengal strains have a short, \"semi-rough\" O side chain and are encapsulated, changes that are likely to have accounted for their ability to cause disease in persons with prior exposure to cholera. These changes in surface structures appear to have resulted from a limited number of genetic modifications. The appearance of V. cholerae O139 Bengal may well herald the beginning of the eighth pandemic of cholera--and underscores the tremendous potential within nature for creation of new strains of \"old\" pathogens.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 1","pages":"41-6"},"PeriodicalIF":0.0,"publicationDate":"1995-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18730395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C V Harding, R Song, J Griffin, J France, M J Wick, J D Pfeifer, H J Geuze
{"title":"Processing of bacterial antigens for presentation to class I and II MHC-restricted T lymphocytes.","authors":"C V Harding, R Song, J Griffin, J France, M J Wick, J D Pfeifer, H J Geuze","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Phagocytosis leads to the destruction of many bacteria and the proteolytic degradation of bacterial antigens within phagolysosomes to produce immunogenic peptides that bind to Class II major histocompatibility (MHC) molecules within vacuolar compartments. On the other hand, Class I MHC molecules bind cytosol-derived peptides, including peptides from bacteria that escape the vacuolar system and penetrate into the cytosol. A recently described pathway may also allow the presentation of peptides from intravacuolar organisms by Class I MHC molecules in some cases. T cell recognition of peptide-MHC complexes then provides the primary basis for specific immunity to protein antigens of bacteria. This article will review the subcellular compartments and mechanisms involved in generating immunogenic peptides, the subcellular localization of MHC molecules that bind these peptides, and bacterial parameters that affect antigen processing.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 1","pages":"1-12"},"PeriodicalIF":0.0,"publicationDate":"1995-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18730392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proteases and bacterial virulence: a view from the trenches.","authors":"J D Goguen, N P Hoe, Y V Subrahmanyam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Many species of pathogenic bacteria produce cell-surface or secreted proteases. These enzymes have high potential to enhance bacterial pathogenesis through degradation of critical host proteins and by mimicking the activity of host regulatory proteases that control important zymogen systems. Although many bacterial proteases have been implicated in virulence, there is currently no system in which both rigorous demonstration of virulence enhancement in vivo and convincing identification of the important substrate molecules has been achieved. The difficulties inherent in addressing these issues is discussed, and several interesting systems under active investigation briefly described. The potential of extracellular protease as targets for drug development is also considered.</p>","PeriodicalId":77176,"journal":{"name":"Infectious agents and disease","volume":"4 1","pages":"47-54"},"PeriodicalIF":0.0,"publicationDate":"1995-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18730396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}