• IMMUNE NETWORK
• /
• v.14 no.4
• /
• pp.187-200
• /
• 2014

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) are the most common cause of genital ulceration in humans worldwide. Typically, HSV-1 and 2 infections via mucosal route result in a lifelong latent infection after peripheral replication in mucosal tissues, thereby providing potential transmission to neighbor hosts in response to reactivation. To break the transmission cycle, immunoprophylactics and therapeutic strategies must be focused on prevention of infection or reduction of infectivity at mucosal sites. Currently, our understanding of the immune responses against mucosal infection of HSV remains intricate and involves a balance between innate signaling pathways and the adaptive immune responses. Numerous studies have demonstrated that HSV mucosal infection induces type I interferons (IFN) via recognition of Toll-like receptors (TLRs) and activates multiple immune cell populations, including NK cells, conventional dendritic cells (DCs), and plasmacytoid DCs. This innate immune response is required not only for the early control of viral replication at mucosal sites, but also for establishing adaptive immune responses against HSV antigens. Although the contribution of humoral immune response is controversial, $CD4^+$ Th1 T cells producing IFN-${\gamma}$ are believed to play an important role in eradicating virus from the hosts. In addition, the recent experimental successes of immunoprophylactic and therapeutic compounds that enhance resistance and/or reduce viral burden at mucosal sites have accumulated. This review focuses on attempts to modulate innate and adaptive immunity against HSV mucosal infection for the development of prophylactic and therapeutic strategies. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses. Thus, we summarized the current evidence of various immune mediators in response to mucosal HSV infection, focusing on the importance of innate immune responses.

• IMMUNE NETWORK
• /
• v.12 no.5
• /
• pp.165-175
• /
• 2012

Vaccination is one of the most effective methods available to prevent infectious diseases. Mucosa, which are exposed to heavy loads of commensal and pathogenic microorganisms, are one of the first areas where infections are established, and therefore have frontline status in immunity, making mucosa ideal sites for vaccine application. Moreover, vaccination through the mucosal immune system could induce effective systemic immune responses together with mucosal immunity in contrast to parenteral vaccination, which is a poor inducer of effective immunity at mucosal surfaces. Among mucosal vaccines, oral mucosal vaccines have the advantages of ease and low cost of vaccine administration. The oral mucosal immune system, however, is generally recognized as poorly immunogenic due to the frequent induction of tolerance against orally-introduced antigens. Consequently, a prerequisite for successful mucosal vaccination is that the orally introduced antigen should be transported across the mucosal surface into the mucosa-associated lymphoid tissue (MALT). In particular, M cells are responsible for antigen up-take into MALT, and the rapid and effective transcytotic activity of M cells makes them an attractive target for mucosal vaccine delivery, although simple transport of the antigen into M cells does not guarantee the induction of specific immune responses. Consequently, development of mucosal vaccine adjuvants based on an understanding of the biology of M cells has attracted much research interest. Here, we review the characteristics of the oral mucosal immune system and delineate strategies to design effective oral mucosal vaccines with an emphasis on mucosal vaccine adjuvants.

• IMMUNE NETWORK
• /
• v.13 no.3
• /
• pp.81-85
• /
• 2013

The mucosal surfaces are constantly exposed to incoming pathogens which can cause infections that result in severe morbidity and/or mortality. Studies have reported that mucosal immunity is important for providing protection against these pathogens and that mucosal vaccination is effective in preventing local infections. For many years, the sublingual mucosa has been targeted to deliver immunotherapy to treat allergic hypersensitivities. However, the potential of vaccine delivery via sublingual mucosal has received little attention until recently. Recent studies exploring such potential have documented the safety and effectiveness of sublingual immunization, demonstrating the ability of sublingual immunization to induce both systemic and mucosal immune responses against a variety of antigens, including soluble proteins, inter particulate antigens, and live-attenuated viruses. This review will summarize the recent findings that address the promising potential of sublingual immunization in proving protection against various mucosal pathogens.

• IMMUNE NETWORK
• /
• v.20 no.6
• /
• pp.44.1-44.19
• /
• 2020

The human body is continuously threatened by pathogens, and the immune system must maintain a balance between fighting infection and becoming over-activated. Mucosal surfaces cover several anatomically diverse organs throughout the body, such as the respiratory and gastrointestinal tracts, and are directly exposed to the external environment. Various pathogens invade the body through mucosal surfaces, making the mucosa the frontline of immune defense. The immune systems of various mucosal tissues display distinctive features that reflect the tissues' anatomical and functional characteristics. This review discusses the cellular components that constitute the respiratory and gastrointestinal tracts; in particular, it highlights the complex interactions between epithelial and immune cells to induce Ag-specific immune responses in the lung and gut. This information on mucosal immunity may facilitate understanding of the defense mechanisms against infectious agents that invade mucosal surfaces, such as severe acute respiratory syndrome coronavirus 2, and provide insight into effective vaccine development.

• Molecules and Cells
• /
• v.21 no.2
• /
• pp.244-250
• /
• 2006

Gangliosides are receptors for various peptides and proteins including neuropeptides, ${\beta}$-amyloid proteins, and prions. Recently, the role of gangliosides in mucosal immunization has attracted attention due to the emerging interest in oral vaccination. Ganglioside GM1 exists in abundance on the surface of the M cells of Peyer's patch, a well-known mucosal immunity induction site. In the present study we identified a peptide ligand for GM1 and tested whether it played a role in immune induction. GM1-binding peptides were selected from a phage-displayed dodecapeptide library and one peptide motif, GWKERLSSWNRF, was fused to the C-terminus of enhanced green fluorescent protein (EGFP). The fusion protein, but not EGFP fused with a control peptide, was concentrated around Peyer's patch after incubation in the lumen of the intestine ex vivo. Furthermore, oral feeding of the fusion protein but not control EGFP induced mucosal and systemic immune responses against EGFP resembling Th2-type immune responses.

• Parasites, Hosts and Diseases
• /
• v.38 no.4
• /
• pp.209-236
• /
• 2000

The last two decades witnessed significant advances in the efforts of immune-parasitologists to elucidate the nature and role of the host mucosal defence mechanisms against intestinal nematode parasites. Aided by recent advances in basic immunology and biotechnology with the concomitant development of well defined laboratory models of infection, immunoparasitologists have more precisely analyzed and defined the different immune effector mechanisms during the infection; resulting in great improvement in our current knowledge and understanding of protective immunity against gastrointestinal (GI) nematode parasites. Much of this current understanding comes from experimental studies in laboratory rodents, which have been used as models of livestock and human GI nematode infections. These rodent studies, which have concentrated on Heligmosomoides polygyrus, Nippostrongylus brasiliensis, Strongyloides ratti/5. venezuelensis. Trichinella spiralis and trichuris muris infections in mice and rats, have helped in defining the types of T cell responses that regulate effector mechanisms and the effector mechanisms responsible for worm expulsion. In addition, these studies bear indications that traditionally accepted mechanisms of resistance such as eosinophilia and IgE responses may not play as important roles in protection as were previously conceived. In this review, we shall, from these rodent studies, attempt an overview of the mucosal and other effector responses against intestinal nematode parasites beginning with the indices of immune protection as a model of the protective immune responses that may occur in animals and man.

• Proceedings of the Korean Society for Applied Microbiology Conference
• /
• 2003.06a
• /
• pp.55-62
• /
• 2003

The mucosal immune system provides a first line of defense against invasion of infectious agents via inhalation, ingestion and sexual contact. For the induction of protective immunity at these invasion sites, one must consider the use of the CMIS, which interconnects inductive tissues, including PP and NALT, and effector tissues of the intestinal, respiratory and genitourinary tracts. In order for the CMIS to induce maximal protective mucosal immunity, co-administration of mucosal adjuvant or use of mucosal antigen delivery vehicle has been shown to be essential. When vaccine antigen is administered via oral or nasal route, antigen-specific Th 1 and Th2 cells, cytotoxic T lymphocytes(CTLs) and IgA B cell responses are effectively induced by the CMIS. In the early stages of induction of mucosal immune response, the uptake of orally or nasally administered antigens is achieved through a unique set of antigen-sampling cells, M cells located in follicle-associated epithelium(FAE) of inductive sites. After successful uptake, the antigens are immediately processed and presented by the underlying DCs for the generation of antigen-specific T cells and IgA committed B cells. These antigen-specific lymphocytes are then home to the distant mucosal effector tissues for the induction of antigen-specific humoral(e.g., IgA) and cell-mediated (e.g., CTL and Th1) immune responses in order to form the first line of defense. Elucidation of the molecular/cellular characteristics of the immunological sequence of mucosal immune response beginning from the antigen sampling and processing/presentation by M cells and mucosal DCs followed by the effector phase with antigen-specific lymphocytes will greatly facilitate the design of a new generation of effective mucosal antigen-specific lymphocytes will greatly facilitate the design of a new generation of a new generation of effective mucosal adjuvants and of a vaccine deliver vehicle that maximizes the use of the CMIS.

• Korean Journal of Veterinary Research
• /
• v.53 no.4
• /
• pp.199-205
• /
• 2013

Avian pathogenic Escherichia coli (APEC) is a causative agent for a number of extra intestinal diseases and account for significant losses to the poultry industry. Since protective immunity against APEC is largely directed to virulence antigens, we have individually expressed four different viulence antigens, papA, papG, IutA, and CS31A, using an attenuated Salmonella Typhimurium and a plasmid pBB244. Following oral immunization of mice with combination of two or four of these strains, serum IgG and mucosal IgA responses were elicited against each antigen represented in the mixture. The antigen-specific mucosal IgA responses were significantly higher in the group of mice immunized with the heat-labile Escherichia coli enterotoxin B subunit (LTB) strain than those in the group of mice immunized without the LTB strain. While, there was no significant difference between these two groups in antigen-specific serum IgG responses. The results showed that LTB could act as mucosal immune adjuvant. To assess the nature of immunity, the distribution of antigen-specific IgG isotypes was analyzed. All groups promoted Th1-type immunity as determined by the IgG2a/IgG1 ratio. Thus, our findings provided evidence that immunization with a combination of several vaccine strains is one of the strategies of developing effective vaccines against APEC.

• Korean Journal of Poultry Science
• /
• v.26 no.2
• /
• pp.131-144
• /
• 1999

Coccidiosis, an intestinal infection caused by intracellular protozoan parasites belonging to several different species of Eimeria seriously impairs the growth and feed utilization of livestock and poultry. Due to complex life cycle of organism and intricate host immune responses to Elmeria, coccidia vaccine development has been difficult. Understanding of basic imunobiology of pertinent host-parasite interactions is necessary for the development of novel control strategy. Although chickens infected with Eimeria spp. produce parasite-specific antibodies in both the circulation and mucosal secretions, antibody mediated responses play a minor role in protection gainst coccidiosis. Rather, increasing evidence show that cell-mediated immunity plays a major role in resistance to coccidiosis. T-lymphocytes appear to respond to coccidiosis both through cytokine production and a direct cytotoxic attack on infected cells. The exact mechanisms by which T-cells eliminate the parasites, however, remain to be investigated. Since it is crucial to understand the intestinal immune system in order to develop an immunological control strategy against any intestinal immune system in order to develop an immunological control strategy against any intestinal diseases, this presentation will summarize our current understanding of the avian intestinal immune system and mucosal immune responses to Eimeria, to provide a conceptual overview of the complex molecular and cellular events involved in intestinal immune responses to enteric pathogens.

• IMMUNE NETWORK
• /
• v.15 no.1
• /
• pp.44-49
• /
• 2015

Interactions between microbes and epithelial cells in the gastrointestinal tract are closely associated with regulation of intestinal mucosal immune responses. Recent studies have highlighted the modulation of mucosal immunity by microbe-derived molecules such as ATP and short-chain fatty acids. In this study, we undertook to characterize the expression of the ATP-gated $P2X_7$ receptor ($P2X_7R$) on M cells and its role in gastrointestinal mucosal immune regulation because it was poorly characterized in Peyer's patches, although purinergic signaling via $P2X_7R$ and luminal ATP have been considered to play an important role in the gastrointestinal tract. Here, we present the first report on the expression of $P2X_7R$ on M cells and characterize the role of $P2X_7R$ in immune enhancement by ATP or LL-37.