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The Journal of Experimental Medicine May 2017Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the... (Review)
Review
Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.
Topics: Adaptation, Physiological; Animals; Antibody Formation; Humans; Immune Tolerance; Intestinal Mucosa; Lymphocytes; T-Lymphocytes, Regulatory
PubMed: 28432200
DOI: 10.1084/jem.20162014 -
Expert Opinion on Biological Therapy Jun 2016Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and... (Review)
Review
INTRODUCTION
Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the CNS and results in neurological disability. Existing immunomodulatory and immunosuppressive approaches lower the number of relapses but do not cure or reverse existing deficits nor improve long-term disability in MS patients.
AREAS COVERED
Monogenic antibodies were described as treatment options for MS, however the immunogenicity of mouse antibodies hampered the efficacy of potential therapeutics in humans. Availability of improved antibody production technologies resulted in a paradigm shift in MS treatment strategies. In this review, an overview of immunotherapies for MS that use conventional monoclonal antibodies reactive to immune system and their properties and mechanisms of action will be discussed, including recent advances in MS therapeutics and highlight natural autoantibodies (NAbs) that directly target CNS cells.
EXPERT OPINION
Recent challenges for MS therapy are the identification of relevant molecular and cellular targets, time frame of treatment, and antibody toxicity profiles to identify safe treatment options for MS patients. The application of monoclonal antibody therapies with better biological efficacy associated with minimum side effects possesses huge clinical potential. Advances in monoclonal antibody technologies that directly target cells of nervous system may promote the CNS regeneration field from bench to bedside.
Topics: Animals; Antibodies, Monoclonal; Antibody Formation; Humans; Immunosuppressive Agents; Immunotherapy; Multiple Sclerosis
PubMed: 26914737
DOI: 10.1517/14712598.2016.1158809 -
Pharmaceutical Research Jun 2009Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic... (Review)
Review
Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These immunological events can compromise the efficacy and safety of these systems by changing the pharmacokinetics, biodistribution and targeting capability of DDS, and by inducing hypersensitivity reactions. Antibodies induced by administration of DDS can be directed against the carrier material, the drug and/or targeting ligands associated with the DDS. Complement activation and opsonization of DDS, which may or may not be associated with antibody formation, may lead to accelerated clearance, hypersensitivity reactions and formation of membrane attack complexes resulting in premature release of the drug. Also platelets have been reported to play a role in DDS immunogenicity. Despite our curtailed understanding of the relationships between physicochemical characteristics and immunogenicity of DDS, several risk factors have been identified. Insight into these factors should be employed in the development of novel DDS with low immunological risk.
Topics: Animals; Antibody Formation; Complement Activation; Drug Carriers; Drug Hypersensitivity; Humans; Injections; Platelet Activation
PubMed: 19247815
DOI: 10.1007/s11095-009-9855-9 -
Environmental Health Perspectives Dec 19952,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and structurally similar halogenated aromatic hydrocarbons cause a broad range of immunologic effects in experimental animals... (Review)
Review
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and structurally similar halogenated aromatic hydrocarbons cause a broad range of immunologic effects in experimental animals including decreased host resistance to infectious disease and suppressed humoral and cell-mediated immune responses. In the mouse, TCDD immunotoxicity has been shown to be an aryl hydrocarbon (Ah) receptor-dependent process. However, despite considerable research, the biochemical and molecular alterations that occur subsequent to Ah receptor activation that lead to altered immune reactivity remain to be elucidated. In addition to immune suppression, TCDD promotes inflammatory responses. This effect may result from an upregulation of the production of inflammatory cytokines such as interleukin-1 and tumor necrosis factor. Nonhuman primates exposed to TCDD show suppressed antibody responses and changes in lymphocyte subsets in the peripheral blood. The immunotoxic effects of TCDD in humans are poorly characterized, and few studies have examined the immune status of individuals with known, documented exposure to TCDD. It is important for laboratory research to focus on defining TCDD-sensitive immunologic biomarkers in animal models that can also be used in human subjects. Understanding the mechanisms that underlie species differences in TCDD immunotoxicity is also of critical importance for extrapolation of effects seen in laboratory animals to man.
Topics: Animals; Antibody Formation; Child; Humans; Immune System; Immunity, Cellular; Mice; Mice, Inbred C57BL; Polychlorinated Dibenzodioxins; Primates; Rats; Research; Toxicity Tests
PubMed: 8635439
DOI: 10.1289/ehp.95103s947 -
African Health Sciences Jun 2016Antibodies are essential part of vertebrates' adaptive immune system; they can now be produced by transforming plants with antibody-coding genes from mammals/humans.... (Review)
Review
BACKGROUND
Antibodies are essential part of vertebrates' adaptive immune system; they can now be produced by transforming plants with antibody-coding genes from mammals/humans. Although plants do not naturally make antibodies, the plant-derived antibodies (plantibodies) have been shown to function in the same way as mammalian antibodies.
METHODS
PubMed and Google search engines were used to download relevant publications on plantibodies in medical and veterinary fields; the papers were reviewed and findings qualitatively described.
RESULTS
The process of bioproduction of plantibodies offers several advantages over the conventional method of antibody production in mammalian cells with the cost of antibody production in plants being substantially lesser. Contrary to what is possible with animal-derived antibodies, the process of making plantibodies almost exclusively precludes transfer of pathogens to the end product. Additionally, plants not only produce a relatively high yield of antibodies in a comparatively faster time, they also serve as cost-effective bioreactors to produce antibodies of diverse specificities.
CONCLUSION
Plantibodies are safe, cost-effective and offer more advantages over animal-derived antibodies. Methods of producing them are described with a view to inspiring African scientists on the need to embrace and harness this rapidly evolving biotechnology in solving human and animal health challenges on the continent where the climate supports growth of diverse plants.
Topics: Animals; Antibody Formation; Health Status; Humans; Immunomodulation; Nigeria; Plantibodies
PubMed: 27605982
DOI: 10.4314/ahs.v16i2.35 -
Clinical Cancer Research : An Official... Nov 2021The role of B cells in the tumor microenvironment and B-cell-mediated antitumor immune responses remains relatively understudied. Recent seminal studies have discovered... (Review)
Review
The role of B cells in the tumor microenvironment and B-cell-mediated antitumor immune responses remains relatively understudied. Recent seminal studies have discovered that B cells and associated tertiary lymphoid structures correlate with responses to checkpoint blockade immunotherapy and are prognostic for overall survival of cancer patients. B-cell subsets have remarkable functional diversity and include professional antigen-presenting cells, regulatory cells, memory populations, and antibody-producing plasma cells. Importantly, secreted antibodies can independently activate innate immune responses and induce the cancer immunity cycle. Thus, B cells and B-cell-mediated antibody responses comprise the largely underappreciated second arm of the adaptive immune system and certainly deserve further attention in the field of oncology. Here, we review the known functions of B cells in the tumor microenvironment, the contribution of B cells to the antitumor activity of immunotherapies, and the role of B cells in the overall survival of cancer patients.
Topics: Animals; Antibody Formation; Antigen-Presenting Cells; B-Lymphocytes; Biomarkers; Disease Management; Humans; Immune Checkpoint Inhibitors; Immunomodulation; Lymphopoiesis; Molecular Targeted Therapy; Neoplasms; Prognosis; Treatment Outcome; Tumor Microenvironment
PubMed: 34230025
DOI: 10.1158/1078-0432.CCR-21-0697 -
American Journal of Respiratory and... Dec 2022
Topics: Humans; Matrix Metalloproteinase 12; Antibody Formation; Asthma; Lung
PubMed: 35944138
DOI: 10.1164/rccm.202109-2082LE -
Signal Transduction and Targeted Therapy Jan 2023
Topics: Antibody Formation
PubMed: 36611028
DOI: 10.1038/s41392-022-01305-3 -
Journal of Pharmaceutical Sciences May 2016The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that... (Review)
Review
The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule, and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review, we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity.
Topics: Animals; Antibody Formation; Humans; Immunogenetic Phenomena; Immunoglobulin G; Immunoproteins; Mice; Mice, Transgenic; Models, Animal; Protein Aggregates; Species Specificity
PubMed: 27044944
DOI: 10.1016/j.xphs.2016.02.031 -
Frontiers in Immunology 2019Vaccines play a vital role in protecting our communities against infectious disease. Unfortunately, some vaccines provide only partial protection or in some cases... (Review)
Review
Vaccines play a vital role in protecting our communities against infectious disease. Unfortunately, some vaccines provide only partial protection or in some cases vaccine-mediated immunity may wane rapidly, resulting in either increased susceptibility to that disease or a requirement for more booster vaccinations in order to maintain immunity above a protective level. The durability of antibody responses after infection or vaccination appears to be intrinsically determined by the structural biology of the antigen, with multivalent protein antigens often providing more long-lived immunity than monovalent antigens. This forms the basis for the Imprinted Lifespan model describing the differential survival of long-lived plasma cell populations. There are, however, exceptions to this rule with examples of highly attenuated live virus vaccines that are rapidly cleared and elicit only short-lived immunity despite the expression of multivalent surface epitopes. These exceptions have led to the concept that multivalency alone may not reliably determine the duration of protective humoral immune responses unless a minimum number of long-lived plasma cells are generated by reaching an appropriate antigenic threshold of B cell stimulation. Examples of long-term and in some cases, potentially lifelong antibody responses following immunization against human papilloma virus (HPV), Japanese encephalitis virus (JEV), Hepatitis B virus (HBV), and Hepatitis A virus (HAV) provide several lessons in understanding durable serological memory in human subjects. Moreover, studies involving influenza vaccination provide the unique opportunity to compare the durability of hemagglutinin (HA)-specific antibody titers mounted in response to antigenically repetitive whole virus (i.e., multivalent HA), or detergent-disrupted "split" virus, in comparison to the long-term immune responses induced by natural influenza infection. Here, we discuss the underlying mechanisms that may be associated with the induction of protective immunity by long-lived plasma cells and their importance in future vaccine design.
Topics: Antibody Formation; Humans; Immunologic Memory; Vaccines
PubMed: 31118935
DOI: 10.3389/fimmu.2019.00956