만성비부비동염의 병인에서 선천성면역의 역할

모지훈 대한비과학회 2014 Journal of rhinology Vol.21 No.1

Chronic rhinosinusitis (CRS) is a multifactorial and heterogeneous disease, and variousfactors, such as inflammation,infection, fungus, and superantigens, have been proposed to play crucial roles in its pathogenesis. Recently,the dominant mechanismof CRS pathogenesis has shiftedfrom microbial infection and environmental factors to host susceptibility. Host susceptibility relies not only on adaptive immunity, but also on innate immunity, and there has recently been much research into innate immunity. Innate immunity is an evolutionally conserved immunesystem that recognizes microbial signature molecules via pattern recognition receptors and is a primary defensesystem that elicits inflammatory and bactericidal responses. Dysfunction of the host response to pathogens is suggested to be involved in pathogenesis of CRS and an irrelevant response of the host’s innate immunity could cause a failure toeradicate the pathogens, thereby contributing to CRS pathogeneses. Among these innate immune systems, toll-like receptors and epithelial barrier functions have been studied extensively, and new players, such as innate lymphoid cells,have beensurfacing. Betterunderstanding of innate immunity couldhelp to investigateand treat this complex disease. In this review, toll-like receptors, epithelial barrier functions, and innate lymphoid cells,among many subjects related to innate immunity,will be discussed in terms of pathogenesis.

Neonatal innate immunity and Toll-like receptor

Yoon, Hye-Sun The Korean Pediatric Society 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.12

The innate immune response is the first line of defense against microbial infections. Innate immunity is made up of the surface barrier, cellular immunity and humoral immunity. In newborn, immunologic function and demands are different to adults. Neonatal innate immunity specifically suppresses Th1-type immune responses, and not Th2-type immune responses, which are enhanced. And the impaired response of macrophages is associated with the defective innate immunity in newborn period. Toll-like receptors (TLRs) play a key roles in the detection of invading pathogens and in the induction of innate immune responses. In newborn, the expression of TLRs is age dependent, so preterm has low expression of TLRs. Also, there are defects in signaling pathways downstream of TLRs. As a consequence, the defects of TLRs activity cause the susceptibility to infection in the neonatal period.

Regulation of Intestinal Homeostasis by Innate Immune Cells

Hisako Kayama,Junichi Nishimura,Kiyoshi Takeda 대한면역학회 2013 Immune Network Vol.13 No.6

The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple innate immune cells have been shown to maintain gut homeostasis by preventing inadequate adaptive immune responses in the murine intestine. Additionally, several innate immune subsets, which promote Th1 and Th17 responses and are implicated in the pathogenesis of IBD, have recently been identified in the human intestinal mucosa. The demonstration of both murine and human intestinal innate immune subsets contributing to regulation of adaptive immunity emphasizes the conserved innate immune functions across species and might promote development of the intestinal innate immunity-based clinical therapy.

선천성 면역반응과 천식

김혜영 ( Hye Young Kim ) 대한천식알레르기학회 2014 Allergy Asthma & Respiratory Disease Vol.2 No.5

Asthma is a complex and heterogeneous disease with several phenotypes. Most studies have focused on allergic asthma associated with allergen sensitization and adaptive immunity. On the other hand, nonallergic asthma is associated with a number of environmental factors such as infection, air pollution, or obesity, and requires innate immunity rather than adaptive immunity. In the lung, a number of innate immune cells and mechanisms have evolved to lead lung inflammation and asthma. These innate mechanisms include innate cytokines and various innate cells, including innate lymphoid cells, natural killer cells, as well as gammadelta T cells, which together produce a wide range of cytokines, independent of adaptive immunity and conventional antigens. Here, we review the most recent works regarding innate immune cells and the mechanisms underlying their role in asthma.(Allergy Asthma Respir Dis 2014;2:317-325)

Regulation of Intestinal Homeostasis by Innate Immune Cells

Kayama, Hisako,Nishimura, Junichi,Takeda, Kiyoshi The Korean Association of Immunobiologists 2013 Immune Network Vol.13 No.6

The intestinal immune system has an ability to distinguish between the microbiota and pathogenic bacteria, and then activate pro-inflammatory pathways against pathogens for host defense while remaining unresponsive to the microbiota and dietary antigens. In the intestine, abnormal activation of innate immunity causes development of several inflammatory disorders such as inflammatory bowel diseases (IBD). Thus, activity of innate immunity is finely regulated in the intestine. To date, multiple innate immune cells have been shown to maintain gut homeostasis by preventing inadequate adaptive immune responses in the murine intestine. Additionally, several innate immune subsets, which promote Th1 and Th17 responses and are implicated in the pathogenesis of IBD, have recently been identified in the human intestinal mucosa. The demonstration of both murine and human intestinal innate immune subsets contributing to regulation of adaptive immunity emphasizes the conserved innate immune functions across species and might promote development of the intestinal innate immunity-based clinical therapy.

Neonatal innate immunity and Toll-like receptor

윤혜선 대한소아청소년과학회 2010 Clinical and Experimental Pediatrics (CEP) Vol.53 No.12

The innate immune response is the first line of defense against microbial infections. Innate immunity is made up of the surface barrier, cellular immunity and humoral immunity. In newborn, immunologic function and demands are different to adults. Neonatal innate immunity specifically suppresses Th1-type immune responses, and not Th2-type immune responses, which are enhanced. And the impaired response of macrophages is associated with the defective innate immunity in newborn period. Toll-like receptors (TLRs) play a key roles in the detection of invading pathogens and in the induction of innate immune responses. In newborn, the expression of TLRs is age dependent, so preterm has low expression of TLRs. Also, there are defects in signaling pathways downstream of TLRs. As a consequence, the defects of TLRs activity cause the susceptibility to infection in the neonatal period.

신생아 감염의 유전학적 감수성

이우령 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

Although advances in neonatal intensive care have led to improved survival, infection continues to be an important cause of death, especially among very low birth weight infants. Humans are constantly exposed to a wide variety of microorganism that can cause infection. In self-defense, the human host has evolved complex protective mechanisms. Immunity can be broadly classified as adaptive acquired immunity or innate immunity. Adaptive immunity is mediated by T and B lymphocytes that proliferate clonally in response to a specific pathogen or antigen. The generation of adaptive immune response requires a number of days. By contrast, the goals of innate immunity are to provide protection in the first minutes to hours after an infectious challenge. Innate immunity was once thought to be a nonspecific response. However, a sophisticated system of receptors, the Toll-like receptors(TRLs), provide considerable specificity for microbial pathogens. The activation of the innate immune system can be a prerequisite for the adaptive immune response. Defects in sensing of pathogens may predispose the host to significant infectious disease. Polymorphisms or mutations in TLRs are associated with increased predisposition to severe and recurrent infections. Recent advances in understanding the molecular basis of the innate immune system led to the identification of certain point mutations of genes involved in the early recognition of bacteria and associated with reduced host response. Much more remains to be learned about expression and function of innate immunity. The completion of the human genome project coupled with rapid advances in the manipulation and analysis of nucleic acids will likely result in an increasing array of techniques by which clinicians more accurately predict the risk of infectious disease and tailor prophylactic therapy accordingly as well as novel therapeutic agents.

Antimicrobial Peptides in Innate Immunity against Mycobacteria

신동민,조은경 대한면역학회 2011 Immune Network Vol.11 No.5

Antimicrobial peptides/proteins are ancient and naturallyoccurring antibiotics in innate immune responses in a variety of organisms. Additionally, these peptides have been recognized as important signaling molecules in regulation of both innate and adaptive immunity. During mycobacterial infection,antimicrobial peptides including cathelicidin, defensin,and hepcidin have antimicrobial activities against mycobacteria,making them promising candidates for future drug development. Additionally, antimicrobial peptides act as immunomodulators in infectious and inflammatory conditions. Multiple crucial functions of cathelicidins in antimycobacterial immune defense have been characterized not only in terms of direct killing of mycobacteria but also as innate immune regulators, i.e., in secretion of cytokines and chemokines,and mediating autophagy activation. Defensin families are also important during mycobacterial infection and contribute to antimycobacterial defense and inhibition of mycobacterial growth both in vitro and in vivo. Hepcidin, although its role in mycobacterial infection has not yet been characterized,exerts antimycobacterial effects in activated macrophages. The present review focuses on recent efforts to elucidate the roles of host defense peptides in innate immunity to mycobacteria.

Regulation of Innate Immunity via MHC Class II-mediated Signaling; Non-classical Role of MHC Class II in Innate Immunity

Hye-Lim Park,남재환 대한미생물학회 2011 Journal of Bacteriology and Virology Vol.41 No.3

MHC class II has long been known to play a classical role in antigen presentation and to act as a signal transducer capable of inducing the adaptive immunity needed to produce pathogen specific antibodies. However, it has recently been revealed that MHC class II can also promote the activation of Toll-like receptor mediated signaling by functioning as an adapter. This means that in addition to its classical function of adaptive immunity, MHC class II also plays an intriguing role in the mechanisms that regulate innate immunity. That being the case, queries inevitably arise regarding the fact that many pathogens have tried to control the induction of MHC class II so as to escape the host immune response. Liu et al (Nat Immunol 2011;12:416-424) demonstrated that intracellular MHC class II interacted with Btk,and that this activated Btk promoted TLR signaling via Myd88 and TRIF. The results of this study provide insight regarding the possibility of a novel role for MHC class II, which was heretofore regarded solely as a classical molecule involved in adaptive immune responses, as a regulator of innate immune responses.

Regulation of Innate Immunity via MHC Class II-mediated Signaling; Non-classical Role of MHC Class II in Innate Immunity

Park, Hye-Lim,Nam, Jae-Hwan 대한미생물학회 2011 Journal of Bacteriology and Virology Vol.41 No.3

자연면역반응(innate immune response)은 병원체의 침입 을 막는 첫 번째 방어선으로 알려져 있으며, 이는 병원균의 독특한 분자적 특징을 인식할 수 있는 Toll-유사 수용체(Toll-like receptor, TLR), Nod-유사 수용체 및 RIG I-유사 수용체를 통해 작용하게 된다. 병원체를 인식한 Toll-유사 수용체의 활성화는 세포 내 연쇄반응을 통해 염증성 사이토카인(inflammatory cytokine)을 생성시키고, 항 원제시세포(B 세포, 수지상세포, 대식세포)의 보조인자 (costimulatory molecule)의 발현을 촉진하여 결과적으로 침입한 병원균을 제거하는데 필수적이다. Major histocompatibility complex (MHC) class II는 항원제거를 위해 항원제시과정에 참여하는 것 이외에도 세포의 증식 및 성숙, 세포사멸에도 관여하는 것으로 알려져 있으나, 본 논문에서는 TLR 매개 신호전달과정에서 MHC class II가 새로운 중요한 조절 요소로 작용함을 확인하여 MHC class II의 새로운 기능에 주안점을 두어 서술하고 있다. Liu 등은 MHC class II가 결핍된 마우스에 병원체가 감염되면 친염증성 사이토카인(proinflammatory cytokine)을 비롯한 type I interferon의 생성이 감소할 뿐만 아니라, 병 원체 감염에 의한 endotoxin shock 또한 감소하는 것을 통해 MHC class II와 TLR 매개 면역반응의 관련성을 증명하였다. 이어 세포표면에 발현하는 MHC class II가 아닌 세포 내 endosome에 위치하는 세포질(intracellular) MHC class II가 보조인자(costimulatory molecule)인 CD40을 통 해 Btk와 상호작용을 하고, 이는 최종적으로 MyD88 및 TRIF와 상호작용을 함으로써 TLR 매개 신호전달을 촉진시킨다는 것을 증명하였다. 이러한 결과는 MHC class II의 새로운 기능을 제시함과 동시에 자연면역반응과 획득면역반응이 서로 밀접한 관계에 놓여 있음을 시사하고 있다. MHC class II has long been known to play a classical role in antigen presentation and to act as a signal transducer capable of inducing the adaptive immunity needed to produce pathogen specific antibodies. However, it has recently been revealed that MHC class II can also promote the activation of Toll-like receptor mediated signaling by functioning as an adapter. This means that in addition to its classical function of adaptive immunity, MHC class II also plays an intriguing role in the mechanisms that regulate innate immunity. That being the case, queries inevitably arise regarding the fact that many pathogens have tried to control the induction of MHC class II so as to escape the host immune response. Liu et al (Nat Immunol 2011;12:416-424) demonstrated that intracellular MHC class II interacted with Btk, and that this activated Btk promoted TLR signaling via Myd88 and TRIF. The results of this study provide insight regarding the possibility of a novel role for MHC class II, which was heretofore regarded solely as a classical molecule involved in adaptive immune responses, as a regulator of innate immune responses.