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1.
Urol Clin North Am ; 47(1): 103-110, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757293

RESUMO

This article provides a comprehensive review of the available data for immunotherapy being used as a salvage treatment in non-muscle-invasive bladder cancer. The literature demonstrates that the immune system has an important role in bladder cancer progression. Initial results from studies using checkpoint inhibitors, recombinant interferon-α2b protein, and oncolytic adenoviruses have shown promising responses with acceptable toxicities. However, the majority of the current data arises from small trials with limited follow-up. There are currently several ongoing studies in this setting, which we await completion, to increase our understanding of immunotherapy as a salvage treatment in non-muscle-invasive bladder cancer.


Assuntos
Imunidade Inata , Fatores Imunológicos/administração & dosagem , Imunoterapia/métodos , Terapia de Salvação/métodos , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Progressão da Doença , Humanos , Invasividade Neoplásica , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
2.
Adv Exp Med Biol ; 1209: 1-6, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728861

RESUMO

Innate immunity plays an important role in the host defense of a variety of different pathogens, and its responses must be tightly regulated to effectively eliminate microbial invasion and avoid immune-related diseases. Autophagy is a homeostatic process that is critical for the bulk degradation of cellular constituents. Recently, accumulating evidence demonstrates the emerging role of the autophagy in the regulation of innate immune responses. In this chapter, we will have a broad overview of the function of autophagy in innate immunity, and briefly introduce the composition of this book and the content of each chapter.


Assuntos
Autofagia , Imunidade Inata
3.
Adv Exp Med Biol ; 1209: 7-22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728862

RESUMO

Autophagy is a fully competent cellular machinery able to carry out the clearance of macromolecules via fusion with the lysosome. Many studies conducted in recent years have revealed that autophagy not only plays a critical role in maintaining cell homeostasis, but can also promote bacterial elimination. Additionally, autophagy exists in most eukaryotic cells including immune cells, such as lymphocytes, neutrophils, eosinophils, mast cells, and natural killer cells. Presently, there are numerous studies focusing on the roles of autophagy in regulating immune response. Autophagy regulates the innate and adaptive immunity by modulating cell differentiation, survival, phagocytosis, antigen presentation, degranulation, and cytokine production. In this chapter, we will summarize how autophagy participates explicitly in the survival and function of the mammalian adaptive and innate immune cells.


Assuntos
Imunidade Adaptativa , Autofagia , Imunidade Inata , Imunidade Adaptativa/imunologia , Animais , Autofagia/imunologia , Sobrevivência Celular/imunologia , Imunidade Inata/imunologia , Mamíferos/imunologia
4.
Adv Exp Med Biol ; 1209: 109-123, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728867

RESUMO

Inflammasome is a molecular platform that mediates the activation of caspases, maturation of interleukin-1 (IL-1) family members, and leads to inflammatory cell death called pyroptosis. It is vital for innate immune responses, providing protection against infectious agents, sterile environmental insults, and host cell damages. Aberrant activation of inflammasome is closely correlated with numerous hereditary and acquired inflammatory disorders. Therefore, a better understanding of how inflammasome is regulated may provide more promising therapeutics for controlling inflammasome-associated diseases. In recent years, it becomes apparent that autophagy, a cellular machinery essential for the recycling of intracellular components and maintenance of cellular homeostasis, acts as a key player in the activation and regulation of inflammasome, and ameliorates symptoms of inflammasome-related diseases. This review will discuss the recent insights into inflammasome activation and regulation mediated by autophagy.


Assuntos
Autofagia , Inflamassomos , Autofagia/imunologia , Caspases/metabolismo , Ativação Enzimática , Humanos , Imunidade Inata/imunologia , Inflamassomos/imunologia , Interleucina-1/imunologia , Piroptose/imunologia
5.
Adv Exp Med Biol ; 1209: 125-144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728868

RESUMO

The production of type I interferons (IFNs) is one of the hallmarks of intracellular antimicrobial program. Typical type I IFN response activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, which results in the transcription of plentiful IFN-stimulated genes (ISGs) to establish the comprehensive antiviral states. Type I IFN signaling should initiate timely to provoke innate and adaptive immune responses for effective elimination of the invading pathogens. Meanwhile, a precise control must come on the stage to restrain the persistent activation of type I IFN responses to avoid attendant toxicity. Autophagy, a conserved eukaryotic degradation system, mediated by a number of autophagy-related (ATG) proteins, plays an essential role in the clearance of invading microorganism and manipulation of type I responses. Autophagy modulates type I IFN responses through regulatory integration with innate immune signaling pathways, and by removing endogenous ligands of innate immune sensors. Moreover, selective autophagy governs the choice of innate immune factors as specific cargoes for degradation, thus tightly monitoring the type I IFN responses. This review will focus on the cross-regulation between autophagy and type I IFN signaling in host defense.


Assuntos
Autofagia , Interações Hospedeiro-Patógeno , Interferon Tipo I , Transdução de Sinais , Animais , Autofagia/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Interferon Tipo I/imunologia , Fatores de Transcrição STAT/imunologia , Transdução de Sinais/imunologia
6.
Adv Exp Med Biol ; 1209: 145-166, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31728869

RESUMO

Autophagy, an evolutionarily conserved cargo degradation process, is responsible to remove superfluous and unwanted cytoplasmic materials and maintain cellular homeostasis. Autophagy can be highly selective and target specific cargoes by utilizing multiple cargo receptors, which bind both ubiquitinated cargoes and autophagosomes. Mounting evidence has revealed the deep involvement of selective autophagy in innate immunity upon pathogen invasion, including eliminating microbial pathogens, initiating the anti-microbe responses, and inhibiting excessive immune responses. Given the importance of selective autophagy in innate immunity, how cargo receptors deliver pathogens and intracellular host constitutes to autophagosomes during infection remains to be elucidated. In this review, we summarize current evidence for the regulation of innate immunity by selective autophagy and try to elucidate the mechanisms employed by cargo receptor network in mediating diverse innate immune responses.


Assuntos
Autofagia , Imunidade Inata , Animais , Autofagossomos , Autofagia/imunologia , Humanos , Imunidade Inata/imunologia , Ubiquitina
7.
Adv Exp Med Biol ; 1197: 11-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732931

RESUMO

The long-standing dogma that immunological memory is the exclusive prerogative of the adaptive immune system has been challenged by emerging evidence that innate immunity can also maintain memory of past events. Such immunological imprinting takes two forms, trained innate immunity and tolerance. Trained immunity involves metabolic and epigenetic adaptations in innate immune cells and their progenitors in the bone marrow upon exposure to certain microbial and/or inflammatory stimuli so that the "trained" cells would be poised to respond much faster and stronger to a subsequent challenge (e.g., a new infection that is not necessarily the same as the earlier one). Conversely, tolerance leads to attenuated immune responses to secondary stimuli. This review focuses on trained immunity and discusses evidence for its existence from lower organisms to humans, its mechanistic underpinnings, and its translational ramifications. Although trained immunity can be considered as an evolutionarily conserved beneficial response against reinfections, in the setting of modern societies with high prevalence of chronic mucosal and systemic inflammatory diseases, trained immunity could also promote maladaptive immune responses that aggravate pathology. Thus, depending on context, innate immune memory could be therapeutically manipulated using defined agonists to either promote innate immune responses (particularly useful for the treatment of infections or chemotherapy-induced myelosuppression) or suppress excessive inflammation in inflammatory and autoimmune diseases.


Assuntos
Imunidade Inata , Imunidade nas Mucosas , Memória Imunológica , Humanos , Imunidade Inata/imunologia , Imunidade nas Mucosas/imunologia , Inflamação
8.
Adv Exp Med Biol ; 1182: 1-37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777013

RESUMO

Ganoderma (Lingzhi) has been used for a long time in China to prevent and treat various diseases. Accumulated studies have demonstrated that the Ganoderma modulates immune function both in vivo and in vitro. The immunomodulating effects of Ganoderma were extensive, including promoting the innate immune function, humoral immunity, and cellular immunity. In particular, G. lucidum polysaccharides may affect immune cells and immune-related cells including B and T lymphocytes, dendritic cells, macrophages, and natural killer cells, with the promotion of immune organ growth, cytokine release, and other immune regulatory functions. Furthermore, cellular and molecular immunomodulatory mechanisms, possible receptors involved, and triggered signaling pathways have also been summarized. However, whole animal experiments are still needed to further establish the mechanism of the immunomodulating effects by Ganoderma. Importantly, evidence-based clinical trials are also needed.


Assuntos
Produtos Biológicos/farmacologia , Imunomodulação , Polissacarídeos/farmacologia , Reishi/química , Animais , China , Humanos , Imunidade Celular , Imunidade Humoral , Imunidade Inata
9.
Zhongguo Zhong Yao Za Zhi ; 44(16): 3384-3390, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602899

RESUMO

Rheumatoid arthritis( RA) is an autoimmune disease characterized by chronic and aggressive polyarthritis. The innate immunity mechanism plays a key role in the pathogenesis of RA. Tripterygium wilfordii and its extracts have regulatory effects on innate immune cells including macrophages,dendritic cells,neutrophils,mast cells,NK cells,NKT cells,etc.,as well as a variety of innate immune molecules including cytokines,adhesion molecules,patterns recognition receptor( PRR) and the complement molecules,showing a regulatory effect in the pathogenesis of RA innate immunity. In this paper,the recent domestic and foreign researches on the pathogenesis of RA with innate immunity involved were reviewed and the research status of T. wilfordii and its extracts on the regulation of innate immunity involved in RA was summarized.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Imunidade Inata , Extratos Vegetais/uso terapêutico , Tripterygium/química , Humanos
10.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31602294

RESUMO

"Infection resisters" are broadly defined as individuals who despite significant exposure to Mycobacterium tuberculosis remain persistently unreactive to conventional detection assays, suggesting that they remain uninfected or rapidly clear their infection early on following exposure. In this review, we highlight recent studies that point to underlying host immune mechanisms that could mediate this natural resistance. We also illustrate some additional avenues that are likely to be differently modulated in resisters and possess the potential to be targeted, ranging from early mycobacterial sensing leading up to subsequent killing. Emerging research in this area can be harnessed to provide valuable insights into the development of novel therapeutic and vaccine strategies against M. tuberculosis.


Assuntos
Imunidade Inata , Mycobacterium tuberculosis , Tuberculose/imunologia , Humanos
11.
Artigo em Chinês | MEDLINE | ID: mdl-31623056

RESUMO

SummaryTobacco smoke exposure has obvious and complex effects on the immune system of the human upper respiratory tract, including pro-inflammatory and anti-immune effects. Exposure to tobacco smoke is closely related to the occurrence and development of allergic rhinitis, the common rhinitis and sinusitis. The innate immune system is influenced by tobacco smoking through its effects on the respiratory mucosa and its adjuncts, natural killer cells, dendritic cells, neutrophils and innate immune receptors. Cigarette smoke can also affect the humoral immunity and cellular immunity, altering the acquired immune condition of the upper respiratory tract. Tobacco smoke exposure promotes the occurrence and development of the upper respiratory tract infectious diseases and allergic diseases by changing the composition of microflora in the upper respiratory tract.


Assuntos
Doenças Respiratórias/epidemiologia , Uso de Tabaco/epidemiologia , Humanos , Imunidade Inata , Nariz , Doenças Respiratórias/imunologia , Rinite , Sinusite , Tabaco , Uso de Tabaco/imunologia
12.
Adv Exp Med Biol ; 1186: 99-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31654387

RESUMO

There is an increasing effort toward generating replacement cells for neuronal application due to the nonregenerative nature of these tissues. While much progress has been made toward developing methodologies to generate these cells, there have been limited improvements in functional restoration. Some of these are linked to the degenerative and often nonreceptive microenvironment that the new cells need to integrate into. In this chapter, we will focus on the status and role of the immune microenvironment of the retina during homeostasis and disease states. We will review changes in both innate and adaptive immunity as well as the role of immune rejection in stem cell replacement therapies. The chapter will end with a discussion of immune-modulatory strategies that have helped to ameliorate these effects and could potentially improve functional outcome for cell replacement therapies for the eye.


Assuntos
Retina , Transplante de Células-Tronco , Imunidade Adaptativa , Microambiente Celular/imunologia , Humanos , Imunidade Inata , Imunomodulação , Neurônios/fisiologia , Retina/imunologia , Degeneração Retiniana/imunologia , Degeneração Retiniana/patologia , Degeneração Retiniana/terapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-31618376

RESUMO

Dermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis.


Assuntos
Dermatomicoses/imunologia , Dermatomicoses/patologia , Imunidade Inata/imunologia , Células de Langerhans/imunologia , Células de Langerhans/patologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Tinha/imunologia , Tinha/patologia , Adulto Jovem
15.
J Microbiol Biotechnol ; 29(10): 1506-1521, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31581380

RESUMO

Tuberculosis, which is caused by Mycobacterium tuberculosis (Mtb), is among the most pressing worldwide problems. Mtb uniquely interacts with innate immune cells through various pattern recognition receptors. These interactions initiate several inflammatory pathways that play essential roles in controlling Mtb pathogenesis. Although the TLR signaling pathways have essential roles in numerous host's immune defense responses, the role of TLR signaling in the response to Mtb infection is still unclear. This review presents discussions on host-Mtb interactions in terms of Mtb-mediated TLR signaling. In addition, we highlight recent discoveries pertaining to these pathways that may help in new immunotherapeutic opportunities.


Assuntos
Mycobacterium tuberculosis/imunologia , Padrões Moleculares Associados a Patógenos/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo , Tuberculose/imunologia , Animais , Citocinas/metabolismo , Humanos , Imunidade Inata , Imunoterapia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/metabolismo , Tuberculose/terapia
16.
Nature ; 574(7776): 45-56, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31578484

RESUMO

New therapies that promote antitumour immunity have been recently developed. Most of these immunomodulatory approaches have focused on enhancing T-cell responses, either by targeting inhibitory pathways with immune checkpoint inhibitors, or by targeting activating pathways, as with chimeric antigen receptor T cells or bispecific antibodies. Although these therapies have led to unprecedented successes, only a minority of patients with cancer benefit from these treatments, highlighting the need to identify new cells and molecules that could be exploited in the next generation of immunotherapy. Given the crucial role of innate immune responses in immunity, harnessing these responses opens up new possibilities for long-lasting, multilayered tumour control.


Assuntos
Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias/imunologia , Neoplasias/terapia , Animais , Humanos , Neoplasias/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia
17.
Adv Exp Med Biol ; 1172: 21-62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628650

RESUMO

Molecules encoded by the Major Histocompatibility Complex (MHC) bind self or foreign peptides and display these at the cell surface for recognition by receptors on T lymphocytes (designated T cell receptors-TCR) or on natural killer (NK) cells. These ligand/receptor interactions govern T cell and NK cell development as well as activation of T memory and effector cells. Such cells participate in immunological processes that regulate immunity to various pathogens, resistance and susceptibility to cancer, and autoimmunity. The past few decades have witnessed the accumulation of a huge knowledge base of the molecular structures of MHC molecules bound to numerous peptides, of TCRs with specificity for many different peptide/MHC (pMHC) complexes, of NK cell receptors (NKR), of MHC-like viral immunoevasins, and of pMHC/TCR and pMHC/NKR complexes. This chapter reviews the structural principles that govern peptide/MHC (pMHC), pMHC/TCR, and pMHC/NKR interactions, for both MHC class I (MHC-I) and MHC class II (MHC-II) molecules. In addition, we discuss the structures of several representative MHC-like molecules. These include host molecules that have distinct biological functions, as well as virus-encoded molecules that contribute to the evasion of the immune response.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Complexo Principal de Histocompatibilidade , Receptores de Antígenos de Linfócitos T , Linfócitos T , Imunidade Adaptativa/imunologia , Animais , Humanos , Imunidade Inata/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Células Matadoras Naturais/química , Receptores de Células Matadoras Naturais/imunologia , Linfócitos T/imunologia
18.
Adv Exp Med Biol ; 1172: 157-188, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31628656

RESUMO

RIG-I-like receptors (RLRs) are an important family of pattern recognition receptors. They activate the immunological responses against viral infections by sensing RNAs in the cytoplasm. Recent studies provide significant insights into the activation and transduction mechanisms of RLRs family (members including RIG-I, MDA5, and LGP2). Here we review our current understanding of the structures of RLRs. Structural characterizations of RLRs family have revealed the mechanism of their actions at molecular level. The activation mechanisms of RIG-I and MDA5 are different, despite both of them have similar domain organizations and bind to dsRNA ligands. RIG-I, but not MDA5, adopts an auto-suppression conformation in the absence of RNA. In addition to ligand triggered receptor oligomerization, the activities of these receptors are also regulated by several posttranslational modifications, especially ubiquitination. Overall, these structural studies play critical roles in promoting the understanding of viral RNA recognition mechanisms by the host innate immune system, which also contribute to the designing of drugs for treatment of viral infection. However, much work remains to be done in studying the signaling pathway of MDA5 and LGP2, particularly by structural biology.


Assuntos
Proteína DEAD-box 58 , RNA Helicases DEAD-box , Imunidade Inata , RNA Viral , Animais , Proteína DEAD-box 58/química , Proteína DEAD-box 58/metabolismo , Humanos , Helicase IFIH1 Induzida por Interferon , RNA de Cadeia Dupla/metabolismo , RNA Viral/análise , RNA Viral/metabolismo , Transdução de Sinais , Viroses/imunologia
19.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(9): 1160-1162, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31657345

RESUMO

OBJECTIVE: Sepsis includes a highly diverse and dynamic mixture of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS). In the past, drugs produced to block the early inflammatory response had little effect on reversing the development of sepsis. Recent studies have shown that the mortality and prognosis of patients are significantly correlated with the immunosuppression of sepsis and the overexpression of co-inhibitory molecules. Programmed death-1 (PD-1) is a recently focused co-inhibitory molecule, which can regulate the functions of a variety of immune cells and participate in innate immunity and acquired immunity. It has important value in risk stratification and prognosis prediction of patients with sepsis, and can be used as one of the intervention targets for immune regulation in sepsis in the future. The role of PD-1 signaling pathway in immunosuppression and its effect on patients' prognosis is reviewed in this article, providing new directions for the treatment of sepsis.


Assuntos
Sepse , Síndrome de Resposta Inflamatória Sistêmica , Humanos , Imunidade Inata , Imunossupressão , Transdução de Sinais
20.
Isr Med Assoc J ; 21(7): 454-459, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507120

RESUMO

BACKGROUND: Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.


Assuntos
Artrite Reumatoide/imunologia , Plaquetas/imunologia , Sinovite/imunologia , Artrite Reumatoide/patologia , Autoimunidade/imunologia , Fibroblastos/imunologia , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Sinovite/patologia , Linfócitos T/imunologia
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