scholarly journals Sequential Immune Responses: The Weapons of Immunity

2015 ◽  
Vol 7 (5) ◽  
pp. 443-449 ◽  
Author(s):  
Charles D. Mills ◽  
Klaus Ley ◽  
Kurt Buchmann ◽  
Johnathan Canton
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Comprehensive Analysis ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Adaptive Responses ◽  
Animal Cells ◽  
Host Protection ◽  
Evolutionarily Conserved ◽  
Different Types

Sequential immune responses (SIR) is a new model that describes what ‘immunity' means in higher animals. Existing models, such as self/nonself discrimination or danger, focus on how immune responses are initiated. However, initiation is not protection. SIR describes the actual immune responses that provide protection. SIR resulted from a comprehensive analysis of the evolution of immune systems that revealed that several very different types of host innate responses occur (and at different tempos) which together provide host protection. SIR1 uses rapidly activated enzymes like the NADPH oxidases and is present in all animal cells. SIR2 is mediated by the first ‘immune' cells: macrophage-like cells. SIR3 evolved in animals like invertebrates and provides enhanced protection through advanced macrophage recognition and killing of pathogens and through other innate immune cells such as neutrophils. Finally, in vertebrates, macrophages developed SIR4: the ability to present antigens to T cells. Though much slower than SIR1-3, adaptive responses provide a unique new protection for higher vertebrates. Importantly, newer SIR responses were added on top of older, evolutionarily conserved functions to provide ‘layers' of host protection. SIR transcends existing models by elucidating the different weapons of immunity that provide host protection in higher animals.

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

scholarly journals The Life Cycle Stages of Pneumocystis murina Have Opposing Effects on the Immune Response to This Opportunistic Fungal Pathogen

2016 ◽  
Vol 84 (11) ◽  
pp. 3195-3205 ◽  
Author(s):  
Heather M. Evans ◽  
Grady L. Bryant ◽  
Beth A. Garvy
Keyword(s):  
Cell Wall ◽  
Life Cycle ◽  
Immune Responses ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Content Type ◽  
Life Cycle Stages ◽  
Ifn Γ

The cell wall β-glucans of Pneumocystis cysts have been shown to stimulate immune responses in lung epithelial cells, dendritic cells, and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with these innate immune cells. Here we report differences in the responses of both neonatal and adult mice to the trophic and cystic life cycle stages of Pneumocystis murina . The adult and neonatal immune responses to infection with Pneumocystis murina trophic forms were less robust than the responses to infection with a physiologically normal mixture of cysts and trophic forms. Cysts promoted the recruitment of nonresident innate immune cells and T and B cells into the lungs. Cysts, but not trophic forms, stimulated increased concentrations of the cytokine gamma interferon (IFN-γ) in the alveolar spaces and an increase in the percentage of CD4 + T cells that produce IFN-γ. In vitro , bone marrow-derived dendritic cells (BMDCs) stimulated with cysts produced the proinflammatory cytokines interleukin 1β (IL-1β) and IL-6. In contrast, trophic forms suppressed antigen presentation to CD4 + T cells, as well as the β-glucan-, lipoteichoic acid (LTA)-, and lipopolysaccharide (LPS)-induced production of interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) by BMDCs. The negative effects of trophic forms were not due to ligation of mannose receptor. Our results indicate that optimal innate and adaptive immune responses to Pneumocystis species are dependent on stimulation with the cyst life cycle stage. Conversely, trophic forms suppress β-glucan-induced proinflammatory responses in vitro , suggesting that the trophic forms dampen cyst-induced inflammation in vivo .

scholarly journals Reprogramming Interferon Regulatory Factor Signaling in Cardiometabolic Diseases

Physiology ◽  
2017 ◽  
Vol 32 (3) ◽  
pp. 210-223 ◽  
Author(s):  
Yaxing Zhang ◽  
Hongliang Li
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Immune Cells ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Regulatory Factor ◽  
Cardiometabolic Diseases ◽  
Evolutionarily Conserved

Interferon regulatory factors (IRFs) are evolutionarily conserved proteins expressed not only in immune cells but also in other tissues and organs outside the immune system. In this review, we discuss mechanisms responsible for IRF-mediated innate immune responses and the function and mechanism of IRFs in cardiometabolic diseases. We focus on the role of IRFs in innate immunity and cardiometabolic homeostasis, and highlight reprogrammed IRF signaling.

Latest Advances in Small Molecule TLR 7/8 Agonist Drug Research

2019 ◽  
Vol 19 (24) ◽  
pp. 2228-2238 ◽  
Author(s):  
David C. McGowan
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Small Molecule ◽  
Immune Cells ◽  
Drug Research ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Small Molecule Activation ◽  
Evolutionarily Conserved ◽  
Recent Developments

Toll-like receptors (TLRs) 7 and 8 play an important role in the activation of innate immune cells in mammals. These evolutionarily conserved receptors serve as important sentinels in response to infection. Activation of TLRs 7 and 8 triggers induction of a Th1 type innate immune response. The emergence of new structural and small molecule information generated in the last decade has contributed enormously to our understanding of this highly sophisticated process of innate immunity signaling. This review will focus on recent developments in the small molecule activation of TLR 7 and 8.

scholarly journals Understanding Host Immunity and the Gut Microbiota Inspires the New Development of Vaccines and Adjuvants

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 163
Author(s):  
Kyosuke Yakabe ◽  
Jun Uchiyama ◽  
Masahiro Akiyama ◽  
Yun-Gi Kim
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Immune Cells ◽  
Current Knowledge ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Mortality And Morbidity ◽  
Complex Interactions ◽  
Immunological Mechanisms ◽  
New Development

Vaccinations improve the mortality and morbidity rates associated with several infections through the generation of antigen-specific immune responses. Adjuvants are often used together with vaccines to improve immunogenicity. However, the immune responses induced by most on-going vaccines and adjuvants approved for human use vary in individuals; this is a limitation that must be overcome to improve vaccine efficacy. Several reports have indicated that the symbiotic bacteria, particularly the gut microbiota, impact vaccine-mediated antigen-specific immune responses and promote the induction of nonspecific responses via the “training” of innate immune cells. Therefore, the interaction between gut microbiota and innate immune cells should be considered to ensure the optimal immunogenicity of vaccines and adjuvants. In this review, we first introduce the current knowledge on the immunological mechanisms of vaccines and adjuvants. Subsequently, we discuss how the gut microbiota influences immunity and highlight the relationship between gut microbes and trained innate immunity, vaccines, and adjuvants. Understanding these complex interactions will provide insights into novel vaccine approaches centered on the gut microbiota.

scholarly journals The Regulation of Inflammation by Innate and Adaptive Lymphocytes

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
David Alex Cronkite ◽  
Tara M. Strutt
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
T And B Cells ◽  
Cell Functions ◽  
Past Experiences

Inflammation plays an essential role in the control of pathogens and in shaping the ensuing adaptive immune responses. Traditionally, innate immunity has been described as a rapid response triggered through generic and nonspecific means that by definition lacks the ability to remember. Recently, it has become clear that some innate immune cells are epigenetically reprogrammed or “imprinted” by past experiences. These “trained” innate immune cells display altered inflammatory responses upon subsequent pathogen encounter. Remembrance of past pathogen encounters has classically been attributed to cohorts of antigen-specific memory T and B cells following the resolution of infection. During recall responses, memory T and B cells quickly respond by proliferating, producing effector cytokines, and performing various effector functions. An often-overlooked effector function of memory CD4 and CD8 T cells is the promotion of an inflammatory milieu at the initial site of infection that mirrors the primary encounter. This memory-conditioned inflammatory response, in conjunction with other secondary effector T cell functions, results in better control and more rapid resolution of both infection and the associated tissue pathology. Recent advancements in our understanding of inflammatory triggers, imprinting of the innate immune responses, and the role of T cell memory in regulating inflammation are discussed.

scholarly journals Innate Immune Defenses in Human Tuberculosis: An Overview of the Interactions betweenMycobacterium tuberculosisand Innate Immune Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jonathan Kevin Sia ◽  
Maria Georgieva ◽  
Jyothi Rengarajan
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Cells ◽  
Public Health Problem ◽  
Human Infection ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Global Public Health ◽  
Bacterial Replication ◽  
Inflammatory Milieu

Tuberculosis (TB) remains a serious global public health problem that results in up to 2 million deaths each year. TB is caused by the human pathogen,Mycobacterium tuberculosis(Mtb), which infects primarily innate immune cells patrolling the lung. Innate immune cells serve as barometers of the immune response against Mtb infection by determining the inflammatory milieu in the lungs and promoting the generation of adaptive immune responses. However, innate immune cells are also potential niches for bacterial replication and are readily manipulated by Mtb. Our understanding of the early interactions between Mtb and innate immune cells is limited, especially in the context of human infection. This review will focus on Mtb interactions with human macrophages, dendritic cells, neutrophils, and NK cells and detail evidence that Mtb modulation of these cells negatively impacts Mtb-specific immune responses. Furthermore, this review will emphasize important innate immune pathways uncovered through human immunogenetic studies. Insights into the human innate immune response to Mtb infection are necessary for providing a rational basis for the augmentation of immune responses against Mtb infection, especially with respect to the generation of effective anti-TB immunotherapeutics and vaccines.

scholarly journals TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Ngiambudulu M. Francisco ◽  
Nai-Jen Hsu ◽  
Roanne Keeton ◽  
Philippa Randall ◽  
Boipelo Sebesho ◽  
...  
Keyword(s):  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Host Protection ◽  
Cerebral Tuberculosis
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