Adaptive Immunity ; Animals ; Humans ; Periodontitis ; immunology

OBJECTIVETo review the senescent remodeling of the immune system with aging and its relevance to the increased susceptibility of the elderly to infectious diseases, along with an outlook on emerging immunological biomarkers.

DATA SOURCESThe data selected were from PubMed with relevant published articles in English or French from 1995 to the present. Searches were made using the terms "immunosenescence" and "aging" paired with the following: "innate immunity", "T-cell", "B-cell", "adaptive immunity" and "biomarkers". Articles were reviewed for additional citations and some information was gathered from web searches.

STUDY SELECTIONArticles on aging of both the innate and adaptive immunity were reviewed, with special attention to the remodeling effect on the ability of the immune system to fight infectious diseases. Articles related to biomarkers of immunosenescence were selected with the goal of identifying immunological biomarkers predisposing the elderly to infections.

RESULTSInnate immunity is generally thought to be relatively well preserved or enhanced during aging compared with adaptive immunity which manifests more profound alterations. However, evidence, particularly in the last decade, reveals that both limbs of the immune system undergo profound remodeling with aging. Reported data on adaptive immunity is consistent and changes are well established but conflicting results about innate immunity were reported between in vivo and in vitro studies, as well as between murine and human studies. Epidemiological data suggests increased predisposition of the elderly to infections, but no compelling scientific evidence has directly linked senescent immune remodeling to this increased susceptibility. Recently, growing interest in identifying immunological biomarkers and defining "immune risk phenotypes/profiles" (IRP) has been expressed. Identification of biomarkers is in its early days and few potential biomarkers have been identified, with the Swedish having defined one IRP based on the adaptive immune response.

CONCLUSIONSAging does not necessarily lead to an unavoidable decline in immune functions. Instead, a complex remodeling occurs. Despite the lack of compelling scientific evidence, senescent immune remodeling surely is a significant contributing factor to the increased risk and severity of infections in the elderly. Although, no immunological biomarker has been formally linked to the increased risk of infections in the elderly, biomarkers remain a promising tool to predict the likelihood of healthy aging, the level of immune competence, and mortality risk in the elderly. Hence, more research is required to define healthy aging and identify immunological biomarkers.

Adaptive Immunity ; immunology ; Aging ; immunology ; physiology ; Animals ; Humans ; Immune System ; immunology ; Immunity, Innate ; immunology ; Infection ; immunology

Toll like receptor (TLR) can specifically recgnize pathogen-associated molecular patterns (PAMPs) and is considered as an important link between innate and adaptive immunity. It has been shown that TLR plays an important role in the pathogenesis and pathophysiology of a variety of skin diseases. Moreover, TLR agonists have exhibited promising therapeutic effects on the disease models and are expected to be novel vaccine adjuvants. Investigations of the underlying mechanism will give new insights into these diseases. This review will discuss the relationship between TLR and pathogenesis and management of some cutaneous diseases.
Adaptive Immunity ; Immunity, Innate ; Signal Transduction ; Skin Diseases ; immunology ; metabolism ; Toll-Like Receptors ; immunology ; metabolism ; physiology

Microbial components and the endogenous molecules released from damaged cells can stimulate germ-line-encoded pattern recognition receptors (PRRs) to transduce signals to the hub of the innate immune signaling network-the adaptor proteins MyD88/TRIF/MAVS/STING/Caspase-1, where integrated signals relay to the relevant transcription factors IRF3/IRF7/NF-κB/ AP-1 and the signal transducer and activator of transcription 6 (STAT6) to trigger the expression of type I interferons and inflammatory cytokines or the assembly of inflammasomes. Most pleiotropic cytokines are secreted and bind to specific receptors, activating the signaling pathways including JAK-STAT for the proliferation, differentiation and functional capacity of immune cells. This review focuses on several critical adaptors in innate immune signaling cascades and recent progress in their molecular mechanisms.
Adaptive Immunity ; Adaptor Proteins, Signal Transducing ; immunology ; metabolism ; Animals ; Humans ; Immunity, Innate ; Signal Transduction ; immunology

MicroRNAs (miRNAs) are critical regulators of the host immune and inflammatory response against bacterial pathogens. In the present review, we discuss target genes, target gene functions, the potential regulatory role of miRNAs in periodontal tissues, and the potential role of miRNAs as biomarkers and therapeutics. In periodontal disease, miRNAs exert control over all aspects of innate and adaptive immunity, including the functions of neutrophils, macrophages, dendritic cells and T and B cells. Previous human studies have highlighted some key miRNAs that are dysregulated in periodontitis patients. In the present study, we mapped the major miRNAs that were altered in our reproducible periodontitis mouse model relative to control animals. The miRNAs that were upregulated as a result of periodontal disease in both human and mouse studies included miR-15a, miR-29b, miR-125a, miR-146a, miR-148/148a and miR-223, whereas miR-92 was downregulated. The association of individual miRNAs with unique aspects of periodontal disease and their stability in gingival crevicular fluid underscores their potential as markers for periodontal disease progression or healthy restitution. Moreover, miRNA therapeutics hold great promise for the future of periodontal therapy because of their ability to modulate the immune response to infection when applied in conjunction with synthetic antagomirs and/or relatively straightforward delivery strategies.
Adaptive Immunity ; Animals ; Biomarkers ; Disease Progression ; Humans ; Immunity, Innate ; MicroRNAs ; genetics ; immunology ; Periodontal Diseases ; genetics ; immunology

Up to 15% of male infertility has an immunological origin, either due to repetitive infections or to autoimmune responses mainly affecting the epididymis, prostate, and testis. Clinical observations and epidemiological data clearly contradict the idea that the testis confers immune protection to the whole male genital tract. As a consequence, the epididymis, in which posttesticular spermatozoa mature and are stored, has raised some interest in recent years when it comes to its immune mechanisms. Indeed, sperm cells are produced at puberty, long after the establishment of self-tolerance, and they possess unique surface proteins that cannot be recognized as self. These are potential targets of the immune system, with the risk of inducing autoantibodies and consequently male infertility. Epididymal immunity is based on a finely tuned equilibrium between efficient immune responses to pathogens and strong tolerance to sperm cells. These processes rely on incompletely described molecules and cell types. This review compiles recent studies focusing on the immune cell types populating the epididymis, and proposes hypothetical models of the organization of epididymal immunity with a special emphasis on the immune response, while also discussing important aspects of the epididymal immune regulation such as tolerance and tumour control.
Adaptive Immunity ; Animals ; Epididymis/immunology* ; Fertility/immunology* ; Genital Neoplasms, Male/immunology* ; Humans ; Immunity, Innate ; Infertility, Male/immunology* ; Male ; Spermatozoa/immunology*

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct "killer" functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.
Adaptive Immunity ; Animals ; Autoimmune Diseases ; immunology ; Humans ; Immune Tolerance ; Immunity, Innate ; Killer Cells, Natural ; immunology ; Liver Diseases ; immunology ; Mice

Neisseria gonorrhoeae (NG), as a pathogen of gonorrhea, is strictly limited to growth on the human host. In case of gonococcal infection, the body may recruit such inflammatory cells as neutrophils to resist the invasion of NG or initiate its adaptive immune response by antigen presentation to eliminate the pathogen. However, a series of immune escape mechanisms of NG make it difficult to clear up the infection. In the innate immune system, NG can not only secrete thermonuclease to degrade neutrophile granulocytes, inhibit respiratory burst to resist killing by neutrophils, activate NLRP3 to prompt the pyronecrosis of inflammatory cells, but also regulate the differentiation of macrophages to reduce the inflammatory response, combine with factor H to evade complement-mediated killing. NG infection can hardly give rise to effective adaptive immune response and immune memory, but can promote TGF-β production to inhibit Th1/Th2-mediated adaptive immune response, bind to CEACAM1 on the B cell surface to promote apoptosis in B cells, and combine with CEACAM1 on the T cell surface to inhibit helper T cell proliferation, which makes it difficult for B cells to produce high-affinity specific antibodies. With the increasing drug-resistance of NG, immunological studies may play a significant role in the development of novel therapies and effective vaccines against the infection.
Adaptive Immunity ; Antibodies ; immunology ; Antigens, CD ; immunology ; Cell Adhesion Molecules ; immunology ; Complement Factor H ; immunology ; Gonorrhea ; immunology ; Humans ; Immune Evasion ; immunology ; Immunity, Innate ; immunology ; Neisseria gonorrhoeae ; immunology

Adaptive Immunity ; Animals ; Female ; Humans ; Immunity, Innate ; Influenza A Virus, H5N1 Subtype ; chemistry ; immunology ; Influenza A virus ; chemistry ; immunology ; Male

Autophagy is a specialized cellular pathway involved in maintaining homeostasis by degrading long-lived cellular proteins and organelles. Recent studies have demonstrated that autophagy is utilized by immune systems to protect host cells from invading pathogens and regulate uncontrolled immune responses. During pathogen recognition, induction of autophagy by pattern recognition receptors leads to the promotion or inhibition of consequent signaling pathways. Furthermore, autophagy plays a role in the delivery of pathogen signatures in order to promote the recognition thereof by pattern recognition receptors. In addition to innate recognition, autophagy has been shown to facilitate MHC class II presentation of intracellular antigens to activate CD4 T cells. In this review, we describe the roles of autophagy in innate recognition of pathogens and adaptive immunity, such as antigen presentation, as well as the clinical relevance of autophagy in the treatment of human diseases.
Adaptive Immunity/immunology/*physiology ; Animals ; Antigen Presentation/immunology/physiology ; Autophagy/immunology/*physiology ; Humans ; Major Histocompatibility Complex/immunology/physiology