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 Augmenting adaptive immunity: progress and challenges in the quantitative engineering and analysis of adaptive immune receptor repertoires

2019 ◽  
Vol 4 (4) ◽  
pp. 701-736 ◽  
Author(s):  
Alex J. Brown ◽  
Igor Snapkov ◽  
Rahmad Akbar ◽  
Milena Pavlović ◽  
Enkelejda Miho ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immunity ◽  
Adaptive Immune System ◽  
Immune Receptor ◽  
Adaptive Immune

The adaptive immune system is a natural diagnostic sensor and therapeutic.

scholarly journals PPARγAgonists in Adaptive Immunity: What Do Immune Disorders and Their Models Have to Tell Us?

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Laurindo Ferreira da Rocha Junior ◽  
Andréa Tavares Dantas ◽  
Ângela Luzia Branco Pinto Duarte ◽  
Moacyr Jesus Barreto de Melo Rego ◽  
Ivan da Rocha Pitta ◽  
...  
Keyword(s):  
Adaptive Immunity ◽  
Inflammatory Diseases ◽  
Cell Lineage ◽  
Adaptive Immune System ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Autoimmune And Inflammatory Diseases ◽  
Ppar Agonists ◽  
T Cell Survival

Adaptive immunity has evolved as a very powerful and highly specialized tool of host defense. Its classical protagonists are lymphocytes of the T- and B-cell lineage. Cytokines and chemokines play a key role as effector mechanisms of the adaptive immunity. Some autoimmune and inflammatory diseases are caused by disturbance of the adaptive immune system. Recent advances in understanding the pathogenesis of autoimmune diseases have led to research on new molecular and therapeutic targets. PPARγare members of the nuclear receptor superfamily and are transcription factors involved in lipid metabolism as well as innate and adaptive immunity. PPARγis activated by synthetic and endogenous ligands. Previous studies have shown that PPAR agonists regulate T-cell survival, activation and T helper cell differentiation into effector subsets: Th1, Th2, Th17, and Tregs. PPARγhas also been associated with B cells. The present review addresses these issues by placing PPARγagonists in the context of adaptive immune responses and the relation of the activation of these receptors with the expression of cytokines involved in adaptive immunity.

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.

scholarly journals How a well-adapting immune system remembers

2018 ◽  
Author(s):  
Andreas Mayer ◽  
Vijay Balasubramanian ◽  
Aleksandra M. Walczak ◽  
Thierry Mora
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Antigen Receptors ◽  
Vaccine Response ◽  
Adaptive Immune ◽  
Future State ◽  
Adaptive Agent ◽  
Memory Pool ◽  
Current Vaccine ◽  
Prior Experiences

An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a mid-life plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.

scholarly journals The gut microbiota is associated with clearance of Clostridium difficile infection independent of adaptive immunity

2019 ◽  
Author(s):  
Jhansi L. Leslie ◽  
Kimberly C. Vendrov ◽  
Matthew L. Jenior ◽  
Vincent B. Young
Keyword(s):  
United States ◽  
Immune Response ◽  
Gut Microbiota ◽  
Adaptive Immunity ◽  
Adaptive Immune Response ◽  
Recurrent Infection ◽  
Adaptive Immune System ◽  
The United States ◽  
Adaptive Immune

AbstractClostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium is the leading single cause of nosocomial infections in the United States. A major risk factor for C. difficile infection (CDI) is prior exposure to antibiotics as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80-90% success rate of fecal microbial transplants in treating recurrent infection. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, Random Forest analysis using only 2 members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract.ImportanceC. difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens as inherent differences in the baseline community structure of animals may bias findings.

3. Adaptive immunity: a voyage of (non-)self-discovery

2017 ◽  
pp. 30-41
Author(s):  
Paul Klenerman
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Lymphocytes ◽  
Adaptive Immunity ◽  
Single Unit ◽  
Adaptive Immune System ◽  
Adaptive Immune ◽  
System A ◽  
Self Discovery ◽  
B And T Lymphocytes

How does the immune system respond to such diverse threats, including viruses never encountered previously by us as a species? The inherent diversity in the immune system can be explained by examining how the adaptive immune system is built, in particular the receptors on B and T lymphocytes. ‘The adaptive immune system: a voyage of (non-)self-discovery’ describes B and T cells, receptors, and the creation of antibodies. Antibody genes are not created as a single unit but are made up from smaller parts, generating many more possible combinations. The antibodies that are created from the genetic template are further honed, becoming highly specific to their target.

Structural Insights into the Evolution of the Adaptive Immune System

2013 ◽  
Vol 42 (1) ◽  
pp. 191-215 ◽  
Author(s):  
Lu Deng ◽  
Ming Luo ◽  
Alejandro Velikovsky ◽  
Roy A. Mariuzza
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune ◽  
Structural Insights

scholarly journals How a well-adapting immune system remembers

2019 ◽  
Vol 116 (18) ◽  
pp. 8815-8823 ◽  
Author(s):  
Andreas Mayer ◽  
Vijay Balasubramanian ◽  
Aleksandra M. Walczak ◽  
Thierry Mora
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Antigen Receptors ◽  
Vaccine Response ◽  
Adaptive Immune ◽  
Future State ◽  
Adaptive Agent ◽  
Memory Pool ◽  
Current Vaccine ◽  
Prior Experiences

An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a midlife plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine-response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs, even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.

scholarly journals Long-term and short-term immunity to SARS-CoV-2: why it matters

2021 ◽  
Vol 42 (1) ◽  
pp. 34
Author(s):  
John Zaunders ◽  
Chansavath Phetsouphanh
Keyword(s):  
Immune Response ◽  
Adaptive Immunity ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Recurrent Infection ◽  
Adaptive Immune System ◽  
Upper Respiratory Tract ◽  
Short Term ◽  
Adaptive Immune ◽  
Tract Infections

The adaptive immune system, regulated by CD4 T cells, is essential for control of many viral infections. Endemic coronavirus infections generally occur as short-term upper respiratory tract infections which in many cases appear to be cleared before adaptive immunity is fully involved, since adaptive immunity takes approximately 1.5–2 weeks to ramp up the response to a primary infection, or approximately 1 week for a recurrent infection. However, the adaptive immune response to SARS-CoV-2 infection will be critical to full recovery with minimal long-lasting effects, and to either prevention of recurrence of infection or at least reduced severity of symptoms. The detailed kinetics of this infection versus the dynamics of the immune response, including in vaccinated individuals, will largely determine these outcomes.

scholarly journals Understanding Early-Life Adaptive Immunity to Guide Interventions for Pediatric Health

2021 ◽  
Vol 11 ◽  
Author(s):  
Eleanor C. Semmes ◽  
Jui-Lin Chen ◽  
Ria Goswami ◽  
Trevor D. Burt ◽  
Sallie R. Permar ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
B Cell ◽  
Adaptive Immunity ◽  
Early Life ◽  
Adaptive Immune System ◽  
Vaccine Adjuvants ◽  
Adaptive Immune Responses ◽  
Pediatric Health ◽  
Adaptive Immune

Infants are capable of mounting adaptive immune responses, but their ability to develop long-lasting immunity is limited. Understanding the particularities of the neonatal adaptive immune system is therefore critical to guide the design of immune-based interventions, including vaccines, in early life. In this review, we present a thorough summary of T cell, B cell, and humoral immunity in early life and discuss infant adaptive immune responses to pathogens and vaccines. We focus on the differences between T and B cell responses in early life and adulthood, which hinder the generation of long-lasting adaptive immune responses in infancy. We discuss how knowledge of early life adaptive immunity can be applied when developing vaccine strategies for this unique period of immune development. In particular, we emphasize the use of novel vaccine adjuvants and optimization of infant vaccine schedules. We also propose integrating maternal and infant immunization strategies to ensure optimal neonatal protection through passive maternal antibody transfer while avoiding hindering infant vaccine responses. Our review highlights that the infant adaptive immune system is functionally distinct and uniquely regulated compared to later life and that these particularities should be considered when designing interventions to promote pediatric health.

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