Abstract:
:The amyloid hypothesis has dominated Alzheimer's disease (AD) research for almost 30 years. This hypothesis hinges on the predominant clinical role of the amyloid beta (Aβ) peptide in propagating neurofibrillary tangles (NFTs) and eventual cognitive impairment in AD. Recent research in the AD field has identified the brain-resident macrophages, known as microglia, and their receptors as integral regulators of both the initiation and propagation of inflammation, Aβ accumulation, neuronal loss, and memory decline in AD. Emerging studies have also begun to reveal critical roles for distinct innate immune pathways in AD pathogenesis, which has led to great interest in harnessing the innate immune response as a therapeutic strategy to treat AD. In this review, we will highlight recent advancements in our understanding of innate immunity and inflammation in AD onset and progression. Additionally, there has been mounting evidence suggesting pivotal contributions of environmental factors and lifestyle choices in AD pathogenesis. Therefore, we will also discuss recent findings, suggesting that many of these AD risk factors influence AD progression via modulation of microglia and immune responses.
journal_name
Immunol Revjournal_title
Immunological reviewsauthors
Ennerfelt HE,Lukens JRdoi
10.1111/imr.12896subject
Has Abstractpub_date
2020-09-01 00:00:00pages
225-246issue
1eissn
0105-2896issn
1600-065Xjournal_volume
297pub_type
杂志文章,评审abstract::Five of the 10 human Toll-like receptors (TLRs) (TLR3, TLR4, TLR7, TLR8, and TLR9), and four of the 12 mouse TLRs (TLR3, TLR4, TLR7, TLR9) can trigger interferon (IFN)-alpha, IFN-beta, and IFN-lambda, which are critical for antiviral immunity. Moreover, TLR3, TLR7, TLR8, and TLR9 differ from TLR4 in two particularly i...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2007.00564.x
更新日期:2007-12-01 00:00:00
abstract::Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), including nitric oxide, are produced in cells by a variety of enzymatic and non-enzymatic mechanisms. At high levels, both types of oxidants are used to kill ingested organisms within phagocytes. At low levels, RNOS may diffuse outside cells whe...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2007.00513.x
更新日期:2007-06-01 00:00:00
abstract::The molecular analysis of the Class II region of the MHC of mice and of humans has to date led to some important conclusions. These regions encode sizeable families of related loci, at least 2 alpha and 6 beta in mice and 6 alpha and 7 beta in man. In addition to the sizeable number of potential molecules that could b...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1985.tb01125.x
更新日期:1985-07-01 00:00:00
abstract::Recent studies on autoimmune ovarian disease (AOD) induced by thymectomy on d3 (d3tx), and AOD induced by immunization with the ovary-specific zona pellucida 3 peptide (pZP3), have yielded the following results. First, female tolerance to pZP3 depends on the persistence of endogenous antigen (Ag). Second, following re...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2001.1820111.x
更新日期:2001-08-01 00:00:00
abstract::Among various strategies to evade the host immune response, some viruses like human cytomegalovirus (HCMV) interfere with surface MHC class I expression and antigen presentation to T lymphocytes. The ability of natural killer (NK) cells to detect MHC class I molecules through inhibitory receptors can be envisaged as a...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2001.1810116.x
更新日期:2001-06-01 00:00:00
abstract::The substantial importance of P-selectin glycoprotein ligand 1 (PSGL-1) in leukocyte trafficking has continued to emerge beyond its initial identification as a selectin ligand. PSGL-1 seemed to be a relatively simple molecule with an extracellular mucin domain extended as a flexible rod, teleologically consistent with...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2009.00797.x
更新日期:2009-07-01 00:00:00
abstract::One of the biggest barriers to achieving allograft tolerance is the presence of immunological memory within the recipient, which confers a faster, more robust immune response that is in most cases more resistant to pharmacologic immunosuppression. This review will identify the mechanisms by which alloreactive T cells ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12824
更新日期:2019-11-01 00:00:00
abstract::This article focuses on four human carboxypeptidases (CPs): two metallo-CPs and two serine CPs. The metallo-CPs are members of the so-called B-type regulatory CP family, as they cleave only the C-terminal basic amino acids Arg or Lys. The plasma membrane-bound CPM and the mainly, but not exclusively, intracellular CPD...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1998.tb01577.x
更新日期:1998-02-01 00:00:00
abstract::Mycobacterium tuberculosis has evolved from a Mycobacterium canettii-like progenitor pool into one of the most successful and widespread human pathogens. The pathogenicity of M. tuberculosis is linked to its ability to secrete/export/release selected mycobacterial proteins, and it is also established that active relea...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12251
更新日期:2015-03-01 00:00:00
abstract::Determination of the crystal structure of class II: peptide complexes has shown that in addition to pocket interactions involving the side chains of the peptide, peptide binding to MHC class II molecules is characterized by a series of hydrogen bonds which are contributed by genetically conserved amino acid residues i...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1999.tb01369.x
更新日期:1999-12-01 00:00:00
abstract::Structures of two intact monoclonal antibodies were solved by X-ray diffraction analysis revealing, in both cases, the dispositions of all segments, as well as the structures of the hinge polypeptides. An IgG1, whose antigen is the drug phenobarbital, assumed a completely different conformation when compared with an I...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1998.tb01186.x
更新日期:1998-06-01 00:00:00
abstract::The co-evolution of papillomaviruses (PV) and their mammalian hosts has produced mechanisms by which PV might avoid specific and non-specific host immune responses. Low level expression of PV proteins in infected basal epithelial cells, together with an absence of inflammation and of virus-induced cell lysis, restrict...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1999.tb01288.x
更新日期:1999-04-01 00:00:00
abstract::The human leukocyte receptor complex (LRC) contains at least 26 genes which belong to the immunoglobulin superfamily The genes include two clusters of immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LIR)/monocyte-macrophage inhibitory receptor (MIR) loci, a cluster of killer cell inhibitor...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2001.1810103.x
更新日期:2001-06-01 00:00:00
abstract::More than 20 years ago, immunologists discovered that resistance and susceptibility to experimental infection with the intracellular protozoan Leishmania major was associated with the development of T-helper 1 (Th1)- and Th2-dominated immune responses, respectively. This infectious disease model was later used to iden...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2010.00983.x
更新日期:2011-03-01 00:00:00
abstract::Pellinos are a family of E3 ubiquitin ligases discovered for their role in catalyzing K63-linked polyubiquitination of Pelle, an interleukin-1 (IL-1) receptor-associated kinase homolog in the Drosophila Toll pathway. Subsequent studies have revealed the central and non-redundant roles of mammalian Pellino-1, Pellino-2...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12298
更新日期:2015-07-01 00:00:00
abstract::Guanine nucleotide binding proteins rapidly cycle between a guanosine diphosphate (GDP)-bound and guanosine triphosphate (GTP)-bound state, and they operate as binary switches that control cell activation in response to environmental cues. GTPases adopt different conformations when binding GTP vs. GDP. The GTP-bound s...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2003.00028.x
更新日期:2003-04-01 00:00:00
abstract::Cells that escape negative selection in the thymus must be inactivated or eliminated in the periphery through a series of mechanisms that include the induction of anergy, dominant suppression by regulatory T cells, and peripheral deletion of self-reactive T cells. Calcium signaling plays a central role in the inductio...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2009.00817.x
更新日期:2009-09-01 00:00:00
abstract::The nuclear factor-κB (NF-κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63-linked polyubiquitination plays a key regulatory role in NF-κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin-binding domains. Ubiquitination is balanced by ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2012.01100.x
更新日期:2012-03-01 00:00:00
abstract::Eosinophils play a prominent pro-inflammatory role in allergic inflammation. Studies utilizing flow chambers, intravital video-microscopy, and cytokine and adhesion molecule-deficient mice have provided important insight into the mechanisms of eosinophil trafficking in inflamed blood vessels and into tissues in vivo. ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2001.790116.x
更新日期:2001-02-01 00:00:00
abstract::Solid tumor therapy with chemotherapeutics greatly depends on the efficiency with which drugs are delivered to tumor cells. The typical characteristics of the tumor physiology promote but also appose accumulation of blood-borne agents. The leaky tumor vasculature allows easy passage of drugs. However, the disorganized...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065X.2008.00619.x
更新日期:2008-04-01 00:00:00
abstract::The pivotal discovery that two chemokine receptors, CCR5 and CXCR4, serve along with the T-cell receptor-interacting CD4 molecule as the principal co-receptors for HIV-1 entry stimulated a search for common genetic polymorphism in their genes which might affect the course of AIDS. Four mutational variants, CCR5-delta3...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2000.17710.x
更新日期:2000-10-01 00:00:00
abstract::A key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we summarize some of the immunological implications of HIV-1 diversit...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12516
更新日期:2017-01-01 00:00:00
abstract::Studies over the last decade uncovered overlapping niches for hematopoietic stem cells (HSCs), multipotent progenitor cells, common lymphoid progenitors, and early B cell progenitors. HSC and lymphoid niches are predominantly composed by mesenchymal progenitor cells (MPCs) and by a small subset of endothelial cells. N...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12749
更新日期:2019-05-01 00:00:00
abstract::During the past several years, we have been studying the circulating TCR gamma delta cells expressed in peripheral lymphoid tissues. Biochemical and molecular characterization of the TCR gamma delta heterodimers present on these TCR gamma delta cells identified 3 TCR gamma proteins, V gamma 2-C gamma 1, V gamma 1.2-C ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1991.tb00585.x
更新日期:1991-04-01 00:00:00
abstract::Mice infected with Listeria monocytogenes (LM) generate protective CD8 cells of varying specificity. One subset, unlike conventional LM-immune CD8 cells, can respond to antigen-presenting cells (APC) treated with heat-killed LM (HKLM). These cells proved to have surprisingly uniform specificity, recognizing a product ...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1997.tb00998.x
更新日期:1997-08-01 00:00:00
abstract::Adaptive immunity has traditionally been considered a unique feature of vertebrate physiology. Unlike innate immune responses, which remain essentially unchanged upon exposure to a recurrent challenge with the same stimulus, adaptive immune cells possess the ability to learn and remember. Thus, secondary adaptive resp...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.0105-2896.2010.00906.x
更新日期:2010-05-01 00:00:00
abstract::αβ T cells are an integral part of protective immunity against pathogens. After precursor cells arise in the adult bone marrow or fetal liver, they migrate to the thymus where they rearrange their T-cell receptor genes (TCR) and undergo selection on the basis of their interactions with ligands expressed by thymic stro...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12095
更新日期:2013-09-01 00:00:00
abstract::Macrophages play essential roles in tissue homeostasis, pathogen elimination, and tissue repair. A defining characteristic of these cells is their ability to efficiently adapt to a variety of abruptly changing and complex environments. This ability is intrinsically linked to a capacity to quickly alter their transcrip...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/imr.12213
更新日期:2014-11-01 00:00:00
abstract::Natural killer (NK) cells of inbred mice reject allogeneic bone-marrow cells, and NK cells of F1 hybrid mice can reject parental bone-marrow cells (hybrid resistance). In some cases these patterns of rejection can be mimicked in vitro by utilizing IL-2 cultured NK effector cells and allogeneic or parental T-lymphoblas...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1111/j.1600-065x.1997.tb00937.x
更新日期:1997-02-01 00:00:00
abstract::Newfound relatives of the classical Fc receptors (FcR) have been provisionally named the Fc receptor homologs (FcRH). The recent identification of eight human and six mouse FcRH genes substantially increases the size and functional potential of the FcR family. The extended family of FcR and FcRH genes spans approximat...
journal_title:Immunological reviews
pub_type: 杂志文章,评审
doi:10.1034/j.1600-065x.2002.19009.x
更新日期:2002-12-01 00:00:00