scholarly journals Kunkel Lecture: Fundamental immunodeficiency and its correction

2017 ◽  
Vol 214 (8) ◽  
pp. 2175-2191 ◽  
Author(s):  
Carl Nathan
Keyword(s):  
Immune System ◽  
Antimicrobial Agents ◽  
Host Immunity ◽  
Host Gene ◽  
Primary Immunodeficiencies ◽  
Human Species ◽  
Adoptive Immunity ◽  
Healthy Host

“Fundamental immunodeficiency” is the inability of the encoded immune system to protect an otherwise healthy host from every infection that could threaten its life. In contrast to primary immunodeficiencies, fundamental immunodeficiency is not rare but nearly universal. It results not from variation in a given host gene but from the rate and extent of variation in the genes of other organisms. The remedy for fundamental immunodeficiency is “adopted immunity,” not to be confused with adaptive or adoptive immunity. Adopted immunity arises from four critical societal contributions to the survival of the human species: sanitation, nutrition, vaccines, and antimicrobial agents. Immunologists have a great deal to contribute to the development of vaccines and antimicrobial agents, but they have focused chiefly on vaccines, and vaccinology is thriving. In contrast, the effect of antimicrobial agents in adopted immunity, although fundamental, is fragile and failing. Immunologists can aid the development of sorely needed antimicrobial agents, and the study of antimicrobial agents can help immunologists discover targets and mechanisms of host immunity.

Immunosensation: Neuroimmune Cross Talk in the Skin

2021 ◽  
Vol 39 (1) ◽  
Author(s):  
Masato Tamari ◽  
Aaron M. Ver Heul ◽  
Brian S. Kim
Keyword(s):  
Immune System ◽  
Host Immunity ◽  
The Body ◽  
Annual Review ◽  
Publication Date ◽  
Protective Behaviors ◽  
Evolutionarily Conserved ◽  
Structural Barrier ◽  
Thermal Stimuli ◽  
Antimicrobial Immunity

Classically, skin was considered a mere structural barrier protecting organisms from a diversity of environmental insults. In recent decades, the cutaneous immune system has become recognized as a complex immunologic barrier involved in both antimicrobial immunity and homeostatic processes like wound healing. To sense a variety of chemical, mechanical, and thermal stimuli, the skin harbors one of the most sophisticated sensory networks in the body. However, recent studies suggest that the cutaneous nervous system is highly integrated with the immune system to encode specific sensations into evolutionarily conserved protective behaviors. In addition to directly sensing pathogens, neurons employ novel neuroimmune mechanisms to provide host immunity. Therefore, given that sensation underlies various physiologies through increasingly complex reflex arcs, a much more dynamic picture is emerging of the skin as a truly systemic organ with highly coordinated physical, immunologic, and neural functions in barrier immunology. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Immune Gene Expression Covaries with Gut Microbiome Composition in Stickleback

mBio ◽  
2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Lauren E. Fuess ◽  
Stijn den Haan ◽  
Fei Ling ◽  
Jesse N. Weber ◽  
Natalie C. Steinel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microbial Communities ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Host Immunity ◽  
Host Gene ◽  
Microbiota Composition ◽  
Host Gene Expression ◽  
Microbiome Composition ◽  
Immune Genes

ABSTRACT Commensal microbial communities have immense effects on their vertebrate hosts, contributing to a number of physiological functions, as well as host fitness. In particular, host immunity is strongly linked to microbiota composition through poorly understood bi-directional links. Gene expression may be a potential mediator of these links between microbial communities and host function. However, few studies have investigated connections between microbiota composition and expression of host immune genes in complex systems. Here, we leverage a large study of laboratory-raised fish from the species Gasterosteus aculeatus (three-spined stickleback) to document correlations between gene expression and microbiome composition. First, we examined correlations between microbiome alpha diversity and gene expression. Our results demonstrate robust positive associations between microbial alpha diversity and expression of host immune genes. Next, we examined correlations between host gene expression and abundance of microbial taxa. We identified 15 microbial families that were highly correlated with host gene expression. These families were all tightly correlated with host expression of immune genes and processes, falling into one of three categories—those positively correlated, negatively correlated, and neutrally related to immune processes. Furthermore, we highlight several important immune processes that are commonly associated with the abundance of these taxa, including both macrophage and B cell functions. Further functional characterization of microbial taxa will help disentangle the mechanisms of the correlations described here. In sum, our study supports prevailing hypotheses of intimate links between host immunity and gut microbiome composition. IMPORTANCE Here, we document associations between host gene expression and gut microbiome composition in a nonmammalian vertebrate species. We highlight associations between expression of immune genes and both microbiome diversity and abundance of specific microbial taxa. These findings support other findings from model systems which have suggested that gut microbiome composition and host immunity are intimately linked. Furthermore, we demonstrate that these correlations are truly systemic; the gene expression detailed here was collected from an important fish immune organ (the head kidney) that is anatomically distant from the gut. This emphasizes the systemic impact of connections between gut microbiota and host immune function. Our work is a significant advancement in the understanding of immune-microbiome links in nonmodel, natural systems.

scholarly journals Primer immunhiány és autoimmun betegségek

2018 ◽  
Vol 159 (23) ◽  
pp. 908-918
Author(s):  
Györgyi Műzes ◽  
Ferenc Sipos
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Primary Immunodeficiency ◽  
Adaptive Immune System ◽  
Infectious Complications ◽  
Primary Immunodeficiencies ◽  
Cellular Mechanisms ◽  
Adaptive Immune ◽  
Solid Malignancies ◽  
Autoimmune Phenomena

Abstract: Primary immunodeficiencies consist of a group of genetically heterogeneous immune disorders affecting distinct elements of the innate and adaptive immune system. Patients with primary immunodeficiency are more prone to develop not only recurrent infections, but non-infectious complications, like inflammatory or granulomatous conditions, lymphoproliferative and solid malignancies, autoinflammatory disorders, and a broad spectrum of autoimmune diseases. The concomitant appearance of primary immunodeficiency and autoimmunity appears to be rather paradoxical, therefore making the diagnosis of immunodeficiency patients with autoimmune complications challenging. Mutations of one or more genes playing a fundamental role in immunoregulation and/or immune tolerance network are thought to be responsible for primary immunodeficiencies. The diverse immunological abnomalities along with the compensatory and excessive sustained inflammatory response result in tissue damage and finally in manifestation of organ-, cell-specific or systemic autoimmune diseases. Several forms of primary immunodeficiency disorders are characterized by a variety of specific autoimmune phenomena. This overview addresses the spectrum of autoimmune diseases associated with primary immunodeficiencies, and explores the molecular and cellular mechanisms underlying abnormalities of the immune system. The case presented finally highlights that both the recognition of autoimmune diseases in association with immunodeficiencies and the diagnosis of immunodefiency in those phenotypes with predominant autoimmunity could be challenging. Orv Hetil. 2018; 159(23): 908–918.

scholarly journals Microbial Modulation of Host Immunity with the Small Molecule Phosphorylcholine

2012 ◽  
Vol 81 (2) ◽  
pp. 392-401 ◽  
Author(s):  
Sarah E. Clark ◽  
Jeffrey N. Weiser
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Small Molecule ◽  
Host Immunity ◽  
Host Responses ◽  
Chop Expression ◽  
Choline Phosphate

ABSTRACTAll microorganisms dependent on persistence in a host for survival rely on either hiding from or modulating host responses to infection. The small molecule phosphorylcholine, or choline phosphate (ChoP), is used for both of these purposes by a wide array of bacterial and parasitic microbes. While the mechanisms underlying ChoP acquisition and expression are diverse, a unifying theme is the use of ChoP to reduce the immune response to infection, creating an advantage for ChoP-expressing microorganisms. In this minireview, we discuss several benefits of ChoP expression during infection as well as how the immune system fights back against ChoP-expressing pathogens.

scholarly journals Cell Shape and Antibiotic Resistance Are Maintained by the Activity of Multiple FtsW and RodA Enzymes in Listeria monocytogenes

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Jeanine Rismondo ◽  
Sven Halbedel ◽  
Angelika Gründling
Keyword(s):  
Cell Wall ◽  
Antibiotic Resistance ◽  
Immune System ◽  
Cell Division ◽  
Listeria Monocytogenes ◽  
Antimicrobial Agents ◽  
Protein Complexes ◽  
Inducible Promoter ◽  
Human Pathogen ◽  
Content Type

ABSTRACT Rod-shaped bacteria have two modes of peptidoglycan synthesis: lateral synthesis and synthesis at the cell division site. These two processes are controlled by two macromolecular protein complexes, the elongasome and divisome. Recently, it has been shown that the Bacillus subtilis RodA protein, which forms part of the elongasome, has peptidoglycan glycosyltransferase activity. The cell division-specific RodA homolog FtsW fulfils a similar role at the divisome. The human pathogen Listeria monocytogenes carries genes that encode up to six FtsW/RodA homologs; however, their functions have not yet been investigated. Analysis of deletion and depletion strains led to the identification of the essential cell division-specific FtsW protein, FtsW1. Interestingly, L. monocytogenes carries a gene that encodes a second FtsW protein, FtsW2, which can compensate for the lack of FtsW1, when expressed from an inducible promoter. L. monocytogenes also possesses three RodA homologs, RodA1, RodA2, and RodA3, and their combined absence is lethal. Cells of a rodA1 rodA3 double mutant are shorter and have increased antibiotic and lysozyme sensitivity, probably due to a weakened cell wall. Results from promoter activity assays revealed that expression of rodA3 and ftsW2 is induced in the presence of antibiotics targeting penicillin binding proteins. Consistent with this, a rodA3 mutant was more susceptible to the β-lactam antibiotic cefuroxime. Interestingly, overexpression of RodA3 also led to increased cefuroxime sensitivity. Our study highlights that L. monocytogenes genes encode a multitude of functional FtsW and RodA enzymes to produce its rigid cell wall and that their expression needs to be tightly regulated to maintain growth, cell division, and antibiotic resistance. IMPORTANCE The human pathogen Listeria monocytogenes is usually treated with high doses of β-lactam antibiotics, often combined with gentamicin. However, these antibiotics only act bacteriostatically on L. monocytogenes, and the immune system is needed to clear the infection. Therefore, individuals with a compromised immune system are at risk to develop a severe form of Listeria infection, which can be fatal in up to 30% of cases. The development of new strategies to treat Listeria infections is necessary. Here we show that the expression of some of the FtsW and RodA enzymes of L. monocytogenes is induced by the presence of β-lactam antibiotics, and the combined absence of these enzymes makes bacteria more susceptible to this class of antibiotics. The development of antimicrobial agents that inhibit the activity or production of FtsW and RodA enzymes might therefore help to improve the treatment of Listeria infections and thereby lead to a reduction in mortality.

An update on direct-fed microbials in broiler chickens in post-antibiotic era

2017 ◽  
Vol 57 (8) ◽  
pp. 1575 ◽  
Author(s):  
Kyung-Woo Lee ◽  
Hyun S. Lillehoj
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Broiler Chickens ◽  
Growth Promotion ◽  
Health Benefit ◽  
Host Immunity ◽  
Feed Additives ◽  
Enteric Diseases ◽  
Naturally Occurring ◽  
Bedding Materials

In a post-antibiotic era, applying dietary alternatives to antibiotics into diets of chickens has become a common practice to improve the productivity and health status of chickens. It is generally accepted that direct-fed microbials (DFMs), defined as a source of viable, naturally occurring microorganisms, as an alternative to antibiotics, have a long history for their safe use and health benefit and are generally regarded for therapeutic, prophylactic and growth-promotion uses in poultry industry. It has been suggested that two primary modes of action by DFMs are balancing gut microbiota and modulating host immunity. Recent findings have suggested that gut microbiota plays an important role in developing immune system and maintaining the homeostasis of mature immune system in mammals and chickens. With the help of molecular and bioinformatics tools, it is now scientifically proven that gut microbiota is diverse, dynamic, and varies according to age, breed, diet composition, environment and feed additives. Broiler chickens are commonly raised on the floor with bedding materials, which facilitates the acquisition of microorganisms present in the bedding materials. Thus, it is expected that environmental factors, including the type of litter, influence host immunity in a positive or negative way. In this regard, adding DFMs into diets of chickens will affect host–microbe interaction, shaping host immunity towards increasing resistance of chickens to enteric diseases.

Evolutionary causes and consequences of diversified CRISPR immune profiles in natural populations

2013 ◽  
Vol 41 (6) ◽  
pp. 1431-1436 ◽  
Author(s):  
Whitney E. England ◽  
Rachel J. Whitaker
Keyword(s):  
Immune System ◽  
Present Article ◽  
Natural Populations ◽  
Host Immunity ◽  
Microbial Populations ◽  
Evolutionary Trajectory ◽  
Host Diversity ◽  
Low Diversity ◽  
Host Pathogen ◽  
Immunity Mechanism

Host–pathogen co-evolution is a significant force which shapes the ecology and evolution of all types of organisms, and such interactions are driven by resistance and immunity mechanisms of the host. Diversity of resistance and immunity can affect the co-evolutionary trajectory of both host and pathogen. The microbial CRISPR (clustered regularly interspaced short palindromic repeats)–Cas (CRISPR-associated) system is one host immunity mechanism which offers a tractable model for examining the dynamics of diversity in an immune system. In the present article, we review CRISPR variation observed in a variety of natural populations, examine the forces which can push CRISPRs towards high or low diversity, and investigate the consequences of various levels of diversity on microbial populations.

Vaccine for SARS-CoV-2- The Facts That We Know So Far

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1500-1506
Author(s):  
Anjali Vashisth ◽  
Gargi Nimbulkar ◽  
Kumar Gaurav Chhabra ◽  
Amit Reche ◽  
Shivani Lanjewar
Keyword(s):  
Immune System ◽  
Symptomatic Relief ◽  
Scientific Work ◽  
The Elderly ◽  
Host Immunity ◽  
Effective Vaccine ◽  
Immune Systems ◽  
Specific Protocol ◽  
Strenuous Work ◽  
Human Immune

The whole world is under the grip of a pandemic of COVID-19, a disease caused by a newly discovered strain of coronavirus and the name given is SARS-CoV-2. The term 'novel' is used for this virus because researches suggest that its origin is from an animal which was transmitted to a human and now is capable of having transmission from human to human. Symptoms of COVID-19 can be mild to severe. Mortality is high in severe cases. Also, this virus is a serious threat to the elderly and people with other systemic illness. There is no specific protocol provided for its treatment and the treatment primarily focuses on symptomatic relief. Human immune systems have never come across this particular type of strain of virus before. As a result, human body has not developed immunity for it moreover no effective vaccine is developed for it at this point of time. But there is an active strenuous work going on to understand more and more about the interaction of host-pathogen, how does host immunity responses to this virus moreover how this pathogen is able to invade the immune system which can be utilised for the development of a vaccine. As the disease is highly infectious, there is an urgent need for the development of a vaccine. Hence this review aims to summarize the undergoing scientific work and research in progress for the development of vaccine and all the advancement that has come in focus for its development.

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