Michael W Russell

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Verified

Michael verified their affiliation via an institutional email.

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• M.A., Ph.D.
• Professor Emeritus at University at Buffalo, State University of New York

Secretory (S) IgA antibodies against severe acute respiratory syndrome (SARS)-CoV-2 are induced in saliva and upper respiratory tract (URT) secretions by natural infection and may be critical in determining the outcome of initial infection. Secretory IgA1 (SIgA1) is the predominant isotype of antibodies in these secretions. Neutralization of SARS-C...

Introduction Several novel vaccine platforms aim at mucosal immunity in the respiratory tract to block SARS-CoV-2 transmission. Standardized methods for mucosal sample collection and quantification of mucosal antibodies are therefore urgently needed for harmonized comparisons and interpretations across mucosal vaccine trials and real-world data. M...

An experimental gonococcal vaccine consisting of outer membrane vesicles (OMVs) and microsphere (ms)-encapsulated interleukin-12 (IL-12 ms) induces Th1-driven immunity, with circulating and genital antibodies to Neisseria gonorrhoeae, after intravaginal (i.vag.) administration in female mice, and generates resistance to vaginal challenge infection....

SARS-CoV-2 is primarily an airborne infection of the upper respiratory tract, which on reaching the lungs causes the severe acute respiratory disease, COVID-19. Its first contact with the immune system, likely through the nasal passages and Waldeyer’s ring of tonsils and adenoids, induces mucosal immune responses revealed by the production of secre...

Martinuzzi et al. provide an explanation, based on due consideration of the operation of the mucosal immune system, for the observation that vaccination of subjects who were previously infected with SARSCoV-2 develop stronger immunity to COVID than uninfected subjects, with enhanced mucosal IgA antibody responses in nasal fluids.

Pelvic inflammatory disease and infertility frequently develop after female genital tract infection with Neisseria gonorrhoeae, but determining their etiology from among various possibilities presents difficulties. Exploitation of serology to identify the causative agent is complicated by numerous factors, and no immunological test currently exists...

The mucosal immune system is the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae. As SARS-CoV-2 initially infects the upper respiratory tract, its first interactions with the immune system must occur predominantly at the respiratory mucosal surfaces, during both...

The concept of immunizing against gonorrhea has received renewed interest because of the recent emergence of strains of Neisseria gonorrhoeae that are resistant to most currently available antibiotics, an occurrence that threatens to render gonorrhea untreatable. However, despite efforts over many decades, no vaccine has yet been successfully devel...

Although the immune compartment of the genital tract is considered a component of the common mucosal system, it displays distinct features characteristic of its physiological and immunological needs not shared by other mucosal sites. These include marked differences in the phenotypes of epithelial cells, lymphocytes, macrophages and dendritic cells...

It has previously been shown that genital tract infection with Neisseria gonorrhoeae in mice does not induce a state of protective immunity against reinfection but instead suppresses the development of adaptive immune responses against N. gonorrhoeae dependent on transforming growth factor beta (TGF-β) and interleukin 10 (IL-10). Intravaginal admin...

Female mice were immunized intravaginally with gonococcal outer membrane vesicles (OMV) plus microencapsulated IL-12, and challenged using an established model of genital infection with Neisseria gonorrhoeae. Whereas sham-immunized and control animals cleared the infection in 10-13 days, those immunized with OMV plus IL-12 cleared infection with ho...

The mucosal surfaces of the body are protected against pathogens and other environmental antigens by the mucosal immune system. This is functionally separate from the circulatory immune system, and represents by far the largest part of the entire immune system. Components include innate and adaptive immune cells and molecules. Specific T and B cell...

The evolution of mucosal immunoglobulins (Ig's) dates to the early origins of the adaptive immune system in jawed vertebrates. The concurrent emergence of genes encoding Ig heavy and light chains and the J chain in cartilaginous fish provided a mechanism for the polymerization of IgM, the primordial mucosal Ig. The emergence of IgT as a specialized...

Although innate immunity came into the research spotlight in the late 1990s when its instructive role in the adaptive immune response was recognized, innate humoral defense factors have a much older history. The exocrine secretions of the body contain a plethora of distinct soluble factors (lysozyme, lactoferrin, peroxidases, proline-rich proteins,...

Sexually transmitted infections (STIs) comprise more than 30 different bacterial, viral, protozoal, and yeast infections acquired during sexual intercourse and therefore directly afflicting the genital tracts or gaining systemic access across the genital mucosae. Effective vaccines have been developed against only two viral STIs (hepatitis B and hu...

This chapter is an overview of the section that follows, dealing with mucosal vaccines against bacterial and viral infections of the gastrointestinal and respiratory tracts and the mouth and infections of veterinary importance. Various strategies have been developed for enhancing mucosal immunization through the use of adjuvants, delivery systems,...

This chapter is an overview of the section that follows, dealing with immunity in the urinary tract including IgA nephropathy, female and male genital tracts, materno-fetal immune interactions, sexually transmitted infections, and the mammary gland and milk.

This chapter is an overview of the section that follows, dealing with the immunobiology and immune protection of the eyes, nose, middle ear, oral cavity, and the tonsils.

Traditional approaches to harnessing the immune system to confront infectious diseases depend on vaccines, which have generally proven highly effective, but for many infections these either are not available or are of limited effectiveness. Although antibiotic therapy has been extremely successful in reducing the burden of bacterial disease, the em...

This chapter serves as an introduction to the book and presents an overview of the mucosal immune system, its major components and functions, and its unique significance with respect to the maintenance of homeostasis and health. Of particular importance is its role in maintaining the commensal microbiota that colonizes most mucosal surfaces, while...

Mucosal Immunology, now in its fourth edition, is the only comprehensive reference covering the basic science and clinical manifestations of mucosal immunology. Most infectious agents enter the body through the various mucous membranes, and many common infections take place in or on mucous membranes, making this subject an area of singular importan...

Uncomplicated genital infection with N. gonorrhoeae does not induce specific protective immunity or immune memory. Our previous studies in a mouse genital tract infection model have demonstrated that N. gonorrhoeae selectively elicits Th17-mediated innate host defenses that it can survive and concomitantly suppresses Th1/Th2-driven adaptive immune...

Intragastric immunization with recombinant chimeric immunogen, SBR-CTA2/B, constructed from the saliva-binding region (SBR) of Streptococcus mutans antigen AgI/II and the A2/B subunits of cholera toxin (CT) induces salivary and circulating antibodies against S. mutans that protect against dental caries. We previously found that SBR-CTA2/B activated...

Gonorrhea remains one of the most frequent infectious diseases, and Neisseria gonorrhoeae is emerging as resistant to most available antibiotics, yet it does not induce a state of specific protective immunity against reinfection. Our recent studies have demonstrated that N. gonorrhoeae proactively suppresses host T-helper (Th) 1/Th2-mediated adapti...

Infection with Neisseria gonorrhoeae triggers an intense inflammatory response characterized by an influx of neutrophils in the genital tract, yet natural gonococcal infection does not induce a state of protective immunity. Our previous studies in a mouse model of N. gonorrhoeae infection demonstrated that transforming growth factor-β (TGF-β) is in...

Infection with Neisseria gonorrhoeae does not induce specific immunity or immune memory. Our previous studies in a murine model of vaginal gonococcal infection showed that innate immunity governed by Th17 cells was a critical aspect of the immune response elicited by this pathogen. Herein we show that N. gonorrhoeae selectively inhibited Th1 and Th...

Murine genital tract infection with Neisseria gonorrhoeae has previously been found to induce IL-17 which is important in both recruitment of neutrophils and prompt clearance of the infection. As IL-22 is another Th17-related cytokine that has been implicated in the immune responses in several infection models, we investigated its role in vaginal g...

SUPPLEMENTARY FIGURE 1 Confocal micrographs of N. gonorrhoeae after incubation with HeLa cells transfected with mouse (upper panels) or human (lower panels) CEACAM1. Left panels stained with anti-gonococcal antibody (red); middle panels stained with anti-mouse (upper panel) or human CEACAM1 (lower panel) antibody (green); right panels showing the m...

Immunoglobulin A (IgA) has a critical role in immune defense particularly at the mucosal surfaces, and is equipped to do so by the unique structural attributes of its heavy chain and by its ability to polymerize. Here, we provide an overview of human IgA structure, describing the distinguishing features of the IgA1 and IgA2 subclasses and mapping t...

Intragastric (i.g.) immunization with recombinant chimeric proteins constructed from the saliva-binding region (SBR) of Streptococcus mutans surface antigen AgI/II and the A2/B subunits of enterobacterial heat-labile enterotoxins has been successfully used to induce salivary and circulating antibodies against S. mutans that have protective potentia...

Unlabelled: The immune response to Neisseria gonorrhoeae is poorly understood, but its extensive antigenic variability and resistance to complement are thought to allow it to evade destruction by the host's immune defenses. We propose that N. gonorrhoeae also avoids inducing protective immune responses in the first place. We previously found that...

Purpose: To investigate cellular pathways of uptake and processing of the recombinant chimeric immunogen SBR-CTA2/B consisting of the saliva-binding region (SBR) of S. mutans AgI/II coupled to cholera toxin A2/B subunits, in comparison with SBR alone. Methods: Amnis ImageStream technology was used to characterize cells from lamina propria (LP), Pey...

It is well-known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoea...

The present invention describes the adjuvant activity of mutants of LT-IIa and LT-IIb enterotoxin which lack ganglioside binding activity. The adjuvant activity of the LT-IIb (T13I) mutant is comparable to that of the wild type LT-IIb. The adjuvant activity of LT-IIa (T34I) mutant is also described which exhibits a late onset adjuvant activity. The...

The genital tract is a unique immunological environment that must support the reproductive function and resist infection. Particularly in the female tract, immunoregulatory and immunosuppressive activities that permit the growth of the fetus create an environment that can readily be exploited by microbes that have become well-adapted to this locati...

Host immune responses, including the characteristic influx of neutrophils, against Neisseria gonorrhoeae are poorly understood; adaptive immunity is minimal and non-protective. We hypothesize that N. gonorrhoeae selectively elicits Th17-dependent responses, which trigger innate defense mechanisms, including neutrophils and antimicrobial proteins, t...

Infection with N. gonorrhoeae triggers an intense inflammatory response characterized by an influx of neutrophils, yet natural infection does not induce effective specific immunity or immune memory. Our previous studies have demonstrated in a murine model of vaginal gonococcal infection that innate immunity governed by Th17 cells was the mainstay o...

An explanation of the principles and mechanisms involved in peaceful co-existence between animals and the huge, diverse, and ever-changing microbiota that resides on their mucosal surfaces represents a challenging puzzle that is fundamental in everyday survival. In addition to mechanical barriers and a variety of innate defense factors, mucosal imm...

The pentameric B subunit of the Escherichia coli LT-IIb enterotoxin (LT-IIb-B(5)) activates TLR2 signaling in macrophages. Herein we demonstrate that LT-IIb-B(5), in contrast to a TLR2-nonbinding point mutant, induces functional activation of bone marrow-derived dendritic cells and stimulates CD4(+) T cell proliferation, activities which suggested...

Infection of the genital tract with Neisseria gonorrhoeae is typically associated with an influx of neutrophils, but the mechanisms underlying this influx are not well understood. The importance of the newly defined lineage of Th17 cells in inflammatory immune responses to infection, including the recruitment of neutrophils, has become increasingly...

Nontypeable Haemophilus influenzae (NTHI) is a significant cause of otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease. Vaccine research for NTHI has focused on the outer membrane proteins (OMPs) of NTHI. The goal of this study was to evaluate mucosal and systemic immune responses to recombinant OMP P2...

The present invention describes the adjuvant activity of mutantsofLT-IaandLT-IIbenterotoxinwhichlackganglio sidebindingactivity.TheadjuvantactivityoftheLT-IIb (T13I)mutantiscomparabletothatofthewildtypeLT-Ib. TheadjuvantactivityofLT-IIa(T34I)mutantisalsodescribed whichexhibitsalateonsetadjuvantactivity.Thesemutants areusefulforenhancingimmunerespon...

Stimulation of mucosal immunity has great potential in vaccinology and immunotherapy. However, the mucosal immune system is more complex than the systemic counterpart, both in terms of anatomy (inductive and effector tissues) and effectors (cells and molecules). Therefore, immunologists entering this field need a precise terminology as a crucial me...

Mucosal administration of Ags induces specific Abs in external secretions and systemic unresponsiveness termed oral or mucosal tolerance. The dominant response depends on the species studied, the nature, dose, frequency, route of Ag application, and the use of adjuvants. The temporal sequence of Ag exposure determines the quality of the ensuing imm...

We have previously demonstrated the full-length gonococcal transferrin binding proteins (TbpA and TbpB) to be promising antigens in the development of a protective vaccine against Neisseria gonorrhoeae. In the current study we employed a genetic chimera approach fusing domains from TbpA and TbpB to the A2 domain of cholera toxin, which naturally bi...

Immunoglobulin A (IgA) is the most enigmatic of immunoglobulins. It is by far the most abundant of human Igs, being present in the blood plasma at concentrations approximating 2–3mg/mL, as well as the dominant isotype in most secretions where its output amounts to some 5–8g/day in adults. Furthermore, its evolutionary origins appear to precede the...

The type IIb heat-labile enterotoxin of Escherichia coli (LT-IIb) and its nontoxic pentameric B subunit (LT-IIb-B(5)) display different immunomodulatory activities, the mechanisms of which are poorly understood. We investigated mechanisms whereby the absence of the catalytically active A subunit from LT-IIb-B(5) renders this molecule immunostimulat...

Insecticidal Cry1A toxins from Bacillus thuringiensis elicit strong humoral immune response in mice. Previously, we showed that an eight hydrophobic motif amino acid substitution in Domain I did not affect the antibody inducing capacity of the Cry1A toxins, on the contrary, it was enhanced after intranasal immunization. In addition, Cry1A mutants (...

The structure and function LT-IIa, a type II heat-labile enterotoxin of Escherichia coli, are closely related to the structures and functions of cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. While LT-IIa is a potent systemic and mucosal adjuvant, recent studies dem...

Cholera toxin (CT) and the type II heat-labile enterotoxins (LT-IIa and LT-IIb) are potent immunological adjuvants which are hypothesized to enhance the production of antibody (Ab)-secreting cells, although their mechanisms of action are not fully understood. The treatment of splenic cells with concanavalin A (ConA) plus CT enhanced the production...

). Several notable differences between the mucosal and systemic compartments of the immune system reflect the different functional requirements of immune responses at mucosal sites where tissue integrity must be maintained in the presence of potentially pathogenic organisms. The predominant Ig type in human mucosal secretions, including saliva, is...

BACKGROUND: Cholera toxin (CT) and the type II heat-labile enterotoxins (LT-IIa and LT-IIb) are potent immunological adjuvants which are hypothesized to enhance the production of antibody (Ab)-secreting cells, although their mechanisms of action are not fully understood. RESULTS: Treatment of splenic cells with concanavalin A (ConA) plus CT enhance...

Previous reports have suggested that peroral delivery of antigens chemically coupled to non-toxic recombinant enterotoxin B subunits, such as the cholera toxin B subunit (CTB), induces tolerance to the antigen that may be abrogated by the toxic enzyme activity of intact enterotoxins, such as cholera toxin (CT). The aim of this study was to examine...

The heat-labile enterotoxins, such as cholera toxin (CT), and the labile toxins types I and II (LT-I and LT-II) of Escherichia coli have been extensively studied for their immunomodulatory properties, which result in the enhancement of immune responses. Despite superficial similarity in structure, in which a toxic A subunit is coupled to a pentamer...

This chapter focuses on microbial strategies specifically related to evasion of immunoglobulin A (IgA) functions, in particular in humans. IgA1 proteases are unique in their specific ability to cleave human IgA1. By attacking a single peptide bond in the IgA1 hinge region, IgA1 proteases eliminate all secondary effector functions of IgA1 antibodies...

The mammalian mucosal immune system is the best characterized, and IgA is the major Ig of most human secretions. The cloning and sequencing of α-chain genes confirm the presence of IgA in several orders of eutherians and in marsupials, monotremes, and birds. The functional characteristics of secretory Igs, such as those defined by "second-order cri...

Innate defense mechanisms help to define the minimal requirements for successful colonization by commensal and pathogenic organisms-those that cannot adapt to these conditions will be incapable of maintaining themselves within the host. Phagocytes represent a major component of innate defense at the cellular level, and all classes of phagocytes, in...

This chapter discusses those sexually transmitted diseases (STDs) that predominantly infect the genital mucosae. Neisseria gonorrhoeae is an exclusively human pathogen. Symptomatic or asymptomatic gonococcal infections may occur at virtually any mucosal site exposed through sexual contact. The Gonococcal infections usually remain localized to the s...

Immunoglobulin A (IgA) is the most heterogeneous of immunoglobulin isotypes, as it occurs in a variety of molecular forms as well as subclasses and allotypes. However, the patterns of heterogeneity vary significantly between different species of mammals and birds. In humans, chimpanzees, gorillas, and gibbons, there are two unique subclasses (IgA1...

BACKGROUND: Administration of antigens (Ags) to the mucosa often fails to elicit strong protective responses. Thus, there is a need to develop new adjuvants for potentiating immune responses to mucosally administered Ags. LT-IIa and LT-IIb, the Type II heat-labile enterotoxins of Escherichia coli, are structurally related to cholera toxin and LT, y...

The transferrin binding proteins (TbpA and TbpB) comprise the gonococcal transferrin receptor and are considered potential antigens for inclusion in a vaccine against Neisseria gonorrhoeae. Intranasal (IN) immunization has shown promise in development of immunity against sexually transmitted disease pathogens, in part due to the induction of antige...

BACKGROUND: Administration of antigens (Ags) to the mucosa often fails to elicit strong protective responses. Thus, there is a need to develop new adjuvants for potentiating immune responses to mucosally administered Ags. LT-IIa and LT-IIb, the Type II heat-labile enterotoxins of Escherichia coli, are structurally related to cholera toxin and LT, y...

BACKGROUND: Administration of antigens (Ags) to the mucosa often fails to elicit strong protective responses. Thus, there is a need to develop new adjuvants for potentiating immune responses to mucosally administered Ags. LT-IIa and LT-IIb, the Type II heat-labile enterotoxins of Escherichia coli, are structurally related to cholera toxin and LT, y...

BACKGROUND: Cholera toxin (CT), LT-IIa, and LT-IIb are potent adjuvants which induce distinct T-helper (Th)-cell cytokine profiles and immunoglobulin G (IgG) subclass and IgA antibody responses. To determine if the distinct immune regulatory effects observed for LT-IIa, LT-IIb, and CT are elicited by binding of the enterotoxins to their cognate gan...

Although the genital tract is considered to be a component of the mucosal immune system, it displays several distinct features not shared by other typical mucosal tissues and external secretions. Both male and female genital tract tissues lack inductive mucosal sites analogous to intestinal Peyer's patches. Consequently, local humoral and cellular...

Cholera toxin (CT), LT-IIa, and LT-IIb are potent adjuvants which induce distinct T-helper (Th)-cell cytokine profiles and immunoglobulin G (IgG) subclass and IgA antibody responses. To determine if the distinct immune regulatory effects observed for LT-IIa, LT-IIb, and CT are elicited by binding of the enterotoxins to their cognate ganglioside rec...

LT-IIa and LT-IIb, the type II heat-labile enterotoxins of Escherichia coli, are closely related in structure and function to cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and E. coli, respectively. Recent studies from our group demonstrated that LT-IIa and LT-IIb are potent systemic and mucosal adjuvants. To determ...

The type II heat-labile enterotoxins (LT-IIa and LT-IIb) of Escherichia coli have an AB5 subunit structure similar to that of cholera toxin (CT) and other type I enterotoxins, despite significant differences in the amino acid sequences of their B subunits and different ganglioside receptor specificities. LT-II holotoxins and their nontoxic B subuni...

The type II heat-labile enterotoxins, LT-IIa and LT-IIb, exhibit potent adjuvant properties. However, little is known about their immunomodulatory activities upon interaction with innate immune cells, unlike the widely studied type I enterotoxins that include cholera toxin (CT). We therefore investigated interactions of LT-IIa and LT-IIb with human...

Background: LT-IIa and LT-IIb, the type II heat-labile enterotoxins of Escherichia coli, are closely related in structure and function to cholera toxin, a type I heat-labile enterotoxin of Vibrio cholerae. LT-IIa, LT-IIb and CT belong to the AB5 family of bacterial enterotoxins which are composed of one A polypeptide and a pentameric array of five...

Studies performed in numerous laboratories over several decades have demonstrated the feasibility of immunizing experimental rodents or primates with protein antigens derived from Streptococcus mutans or Streptococcus sobrinus against oral colonization by mutans streptococci and the development of dental caries. Protection has been attributed to sa...

Quantification of specific nucleic acids plays a key role in the study of gene expression and in the clinical analysis of viral loads such as for human immunodeficiency virus (HIV-1) and hepatitis C virus (HCV). Among methods developed for this purpose, competitive (RT)-PCR, ¹ [polymerase chain reaction (PCR), with or without prior reverse transcri...

A perceptive reader scanning the Contents of this volume will notice that of 16 bacterial infections covered, only one (Borrelia burgdorferi) is normally delivered transcutaneously by arthropod bite; the remaining 15 either directly afflict, or normally invade across a mucosal surface. There is nothing unusual about this, as it applies to the great...

Toll-like receptors (TLR) function as important signal transducers that mediate innate immune and inflammatory responses to pathogens through pattern recognition of virulence molecules. Although TLRs mediate protection against infection, it is also likely that they may have a pathophysiologic role in certain inflammatory diseases, such as atheroscl...

Secretory immunoglobulin (Ig) A (SIgA) is essential in protecting mucosal surfaces. It is composed of at least two monomeric IgA molecules, covalently linked through the J chain, and secretory component (SC). We show here that a dimeric/polymeric IgA (IgAd/p) is more efficient when bound to SC in protecting mice against bacterial infection of the r...

Local application of non-replicating antigens to the female reproductive tract is ineffective in stimulating the common mucosal immune system, and induces only weak genital antibody responses. Studies of immune responses to genital infections such as gonorrhea also support the concept that, lacking mucosal immune inductive sites, the reproductive t...

Human reproductive tracts represent components of the mucosal immune system with unique features. Although secretory IgA is present, IgG is more abundant, and typical mucosa-associated lymphoid tissue for generating common mucosal immune responses is absent. Antibody responses to genital infections or to locally applied vaccines are usually modest,...

Toll-like receptors (TLRs) are important signal transducers that mediate inflammatory reactions induced by microbes through pattern recognition of virulence molecules such as lipopolysaccharide (LPS) and lipoproteins. We investigated whether proinflammatory cytokine responses induced by certain bacterial protein adhesins may also depend on TLRs. In...

Saliva contains an array of nonimmunoglobulin defense factors which are thought to contribute to the protection of the hard and soft tissue surfaces of the oral cavity by modulating microbial colonization and metabolism. Here we report the discovery of a putative innate defense factor in human saliva that inhibits the glucosyltransferase (GTF) of S...

Immune responses and the mechanisms of tolerance to the common dietary antigens bovine gamma globulin (BGG), ovalbumin (OVA), and soybean protein were evaluated in normal human volunteers. Humoral and T cell proliferative responses to these antigens were measurable but low, consistent with immune tolerance. There were limited correlations between r...

Attenuated Salmonella enterica serovar Typhimurium has been used for targeted delivery of recombinant antigens to gut- and nose-associated lymphoid tissues. Contradictory reports have described the effect of preexisting immunity to the antigen delivery vehicle. We decided to examine this discrepancy by studying the effect of immunizing mice by the...

Penile urethral swabs collected from PCR-confirmed Chlamydia trachomatis-infected, C. trachomatis-uninfected, and non-C. trachomatis-infected, nongonococcal urethritis-infected males were analyzed for cytokine, total immunoglobulin (Ig), and specific antibody levels by enzyme-linked immunosorbent assay. Differential cellular components of the swab...