scholarly journals 3D Structural View of Pathogen Recognition by Mammalian Lectin Receptors

2021 ◽  
Vol 8 ◽  
Author(s):  
Noriyoshi Manabe ◽  
Yoshiki Yamaguchi
Keyword(s):  
Binding Sites ◽  
Chemical Structure ◽  
Structural Information ◽  
Current Knowledge ◽  
Adaptive Immune System ◽  
Pathogen Recognition ◽  
Lectin Receptors ◽  
Adaptive Immune ◽  
Species Specific ◽  
Mammalian Lectin

Humans and other mammals resist exogenous pathogens by recognizing them as non-self. How do they do this? The answer lies in the recognition by mammalian lectin receptors of glycans usually found on the surface of pathogens and whose chemical structure is species-specific. Some glycan components, such as galactofuranose, only occur in microbes, and is the principal means by which mammalian lectin receptors recognize non-self. Several lectins may function together as pattern recognition receptors to survey the infecting pathogen before the adaptive immune system is invoked. Most lectins have primary and secondary monosaccharide-binding sites which together determine the specificity of a receptor toward microbial glycans. There may also be a hydrophobic groove alongside the sugar binding sites that increases specificity. Another elaboration is through oligomerization of lectin domains with defined spacing and arrangement that creates high-affinity binding towards multiply-presented glycans on microbes. Microbe-specific polysaccharides may arise through unique sugar linkages. Specificity can come from mammalian receptors possessing a shallow binding site and binding only internal disaccharide units, as in the recognition of mannan by Dectin-2. The accumulation of 3D structural information on lectins receptors has allowed the recognition modes of microbe glycans to be classified into several groupings. This review is an introduction to our current knowledge on the mechanisms of pathogen recognition by representative mammalian lectin receptors.

Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates

2010 ◽  
Vol 391 (7) ◽  
Author(s):  
Roy A. Mariuzza ◽  
C. Alejandro Velikovsky ◽  
Lu Deng ◽  
Gang Xu ◽  
Zeev Pancer
Keyword(s):  
Adaptive Immunity ◽  
Structural Information ◽  
Perfect Match ◽  
Dna Recombination ◽  
Adaptive Immune System ◽  
Antigen Receptors ◽  
Adaptive Immune ◽  
Structural Insights ◽  
Similar Affinity ◽  
Lymphocyte Receptors

Abstract Adaptive immunity in jawless vertebrates is mediated by antigen receptors that are fundamentally different from those of jawed vertebrates. Whereas antibodies and T cell receptors (TCRs) are composed of immunoglobulin (Ig) domains, the variable lymphocyte receptors (VLRs) of jawless fish consist of leucine-rich repeat (LRR) modules. As with antibodies and TCRs, VLRs are assembled by DNA recombination in a process that generates a vast repertoire of receptors. VLRs recognize as diverse an array of particulate and soluble antigens as Ig-based antibodies, and do so with similar affinity and specificity. X-ray crystallographic studies of VLRs in complex with protein and carbohydrate antigens have shown that these LRR-based receptors use nearly all their concave surface to bind ligands, in addition to a highly variable loop in their C-terminal LRR capping module. This structural information, combined with a comprehensive analysis of VLR sequences, has revealed an almost perfect match between antigen-contacting positions and positions with highest sequence diversity. The independent evolution approximately 500 million years ago of LRR-based and Ig-based receptors of comparable diversity and antigen-binding properties provides evidence for the survival value of adaptive immunity in vertebrates.

scholarly journals Coelomocytes: Biology and Possible Immune Functions in Invertebrates with Special Remarks on Nematodes

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
Qudsia Tahseen
Keyword(s):  
Immune System ◽  
Current Knowledge ◽  
Adaptive Immune System ◽  
Infectious Agents ◽  
Immune Functions ◽  
Humoral Factors ◽  
C Elegans ◽  
Adaptive Immune ◽  
Wide Range ◽  
Morphology And Structure

All metazoans are exposed to a wide range of microbes and have evolved complex immune defenses used to repel infectious agents. Coelomocytes play a key role in the defense reactions of most invertebrates. They are involved in important immune functions, such as phagocytosis, encapsulation, graft rejection, and inflammation, as well as the synthesis and secretion of several humoral factors especially in annelids and echinoderms. Coelomocytes in nematodes are variable in shapes from round, ovoid, cuboidal, and spindle-shaped to stellate or branched cells that are found usually at fixed positions in the pseudocoelom. Their number usually varies from 2 to 6. The model nematode,C. eleganslacks an adaptive immune system and the coelomocytes are capable of endocytosis, but their involvement in phagocytosis of bacteria seems unlikely. The aim of this review is to evaluate current knowledge on coelomocytes of invertebrates with special reference to nematodes. The morphology and structure of these coelomocytes are discussed along with their origin. Their relative positions and diversity in different nematode groups have also been discussed and illustrated.

scholarly journals Immune Aging and Immunotherapy in Cancer

2021 ◽  
Vol 22 (13) ◽  
pp. 7016
Author(s):  
Melanie Kaiser ◽  
Maria Donatella Semeraro ◽  
Markus Herrmann ◽  
Gudrun Absenger ◽  
Armin Gerger ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Current Knowledge ◽  
Adaptive Immune System ◽  
Predictive Biomarkers ◽  
Immune Checkpoint Blockade ◽  
Cell Aging ◽  
Immune Functions ◽  
Adaptive Immune ◽  
Age Related

Immune functions decline as we age, while the incidence of cancer rises. The advent of immune checkpoint blockade (ICB) has not only revolutionized cancer therapy, but also spawned great interest in identifying predictive biomarkers, since only one third of patients show treatment response. The aging process extensively affects the adaptive immune system and thus T cells, which are the main target of ICB. In this review, we address age-related changes regarding the adaptive immune system with a focus on T cells and their implication on carcinogenesis and ICB. Differences between senescence, exhaustion, and anergy are defined and current knowledge, treatment strategies, and studies exploring T cell aging as a biomarker for ICB are discussed. Finally, novel approaches to improve immunotherapies and to identify biomarkers of response to ICB are presented and their potential is assessed in a comparative analysis.

Evolution and age characteristics of the innate and adaptive immune system

2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune

scholarly journals Pan-American Lancehead Pit-Vipers: Coagulotoxic Venom Effects and Antivenom Neutralisation of Bothrops asper and B. atrox Geographical Variants

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 78
Author(s):  
Lachlan A. Bourke ◽  
Christina N. Zdenek ◽  
Edgar Neri-Castro ◽  
Melisa Bénard-Valle ◽  
Alejandro Alagón ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Current Knowledge ◽  
Clinical Manifestations ◽  
In Vivo Studies ◽  
Factor X ◽  
Clotting Factors ◽  
Bothrops Asper ◽  
Species Specific

The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothrops atrox are the most medically significant species of snakes in Latin America, both producing a variety of clinical manifestations, including systemic bleeding. These pathophysiological actions are due to the activation by the venom of the blood clotting factors Factor X and prothrombin, thereby causing severe consumptive coagulopathy. Both species are extremely wide-ranging, and previous studies have shown their venoms to exhibit regional venom variation. In this study, we investigate the differential coagulotoxic effects on human plasma of six venoms (four B. asper and two B. atrox samples) from different geographic locations, spanning from Mexico to Peru. We assessed how the venom variation of these venom samples affects neutralisation by five regionally available antivenoms: Antivipmyn, Antivipmyn-Tri, PoliVal-ICP, Bothrofav, and Soro Antibotrópico (SAB). The results revealed both inter- and intraspecific variations in the clotting activity of the venoms. These variations in turn resulted in significant variation in antivenom efficacy against the coagulotoxic effects of these venoms. Due to variations in the venoms used in the antivenom production process, antivenoms differed in their species-specific or geographical neutralisation capacity. Some antivenoms (PoliVal-ICP, Bothrofav, and SAB) showed species-specific patterns of neutralisation, while another antivenom (Antivipmyn) showed geographic-specific patterns of neutralisation. This study adds to current knowledge of Bothrops venoms and also illustrates the importance of considering evolutionary biology when developing antivenoms. Therefore, these results have tangible, real-world implications by aiding evidence-based design of antivenoms for treatment of the envenomed patient. We stress that these in vitro studies must be backed by future in vivo studies and clinical trials before therapeutic guidelines are issued regarding specific antivenom use in a clinical setting.

scholarly journals Structural analysis of the SRP Alu domain from Plasmodium falciparum reveals a non-canonical open conformation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Komal Soni ◽  
Georg Kempf ◽  
Karen Manalastas-Cantos ◽  
Astrid Hendricks ◽  
Dirk Flemming ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Binding Sites ◽  
Signal Recognition Particle ◽  
Signal Recognition ◽  
Closed Conformation ◽  
Open Conformation ◽  
Structural Database ◽  
Alu Rna ◽  
Species Specific ◽  
Protozoan Species

AbstractThe eukaryotic signal recognition particle (SRP) contains an Alu domain, which docks into the factor binding site of translating ribosomes and confers translation retardation. The canonical Alu domain consists of the SRP9/14 protein heterodimer and a tRNA-like folded Alu RNA that adopts a strictly ‘closed’ conformation involving a loop-loop pseudoknot. Here, we study the structure of the Alu domain from Plasmodium falciparum (PfAlu), a divergent apicomplexan protozoan that causes human malaria. Using NMR, SAXS and cryo-EM analyses, we show that, in contrast to its prokaryotic and eukaryotic counterparts, the PfAlu domain adopts an ‘open’ Y-shaped conformation. We show that cytoplasmic P. falciparum ribosomes are non-discriminative and recognize both the open PfAlu and closed human Alu domains with nanomolar affinity. In contrast, human ribosomes do not provide high affinity binding sites for either of the Alu domains. Our analyses extend the structural database of Alu domains to the protozoan species and reveal species-specific differences in the recognition of SRP Alu domains by ribosomes.

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