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1.
Following infection, a virus must battle against the host's immune response. Viruses have developed many ways to escape immune surveillance and downregulate the host's immune response. Some viruses cause a generalized immunosuppression, thereby inhibiting or depressing the immune response towards themselves as well as towards unrelated pathogens. This review will focus on the mechanisms involved in the three main human viral infections causing immunosuppression: measles, human immunodeficiency virus and cytomegalovirus. We will also discuss what has been learned from the extensively studied mouse models of viral-induced immunosuppression: lymphocytic choriomeningitis virus and Rauscher leukemia virus. All of these viruses that induce generalized immunosuppression appear to do so by very similar mechanisms. They hinder antigen presentation to T cells and/or hematopoiesis. We will highlight the similarities in the viral targets as well as present evidence for alternate mechanisms. 相似文献
2.
Immune responses to DNA vaccines 总被引:16,自引:0,他引:16
DNA vaccines, based on plasmid vectors expressing an antigen under the control of a strong promoter, have been shown to induce
protective immune responses to a number of pathogens, including viruses, bacteria and parasites. They have also displayed
efficacy in treatment or prevention of cancer, allergic diseases and autoimmunity. Immunologically, DNA vaccines induce a
full spectrum of immune responses that include cytolytic T cells, T helper cells and antibodies. The immune response to DNA
vaccines can be enhanced by genetic engineering of the antigen to facilitate its presentation to B and T cells. Furthermore,
the immune response can be modulated by genetic adjuvants in the form of vectors expressing biologically active determinants
or by more traditional adjuvants that facilitate uptake of DNA into cells. The ease of genetic manipulation of DNA vaccines
invites their use not only as vaccines but also as research tools for immunologists and microbiologists.
Received 26 October 1998; received after revision 3 December 1998; accepted 3 December 1998 相似文献
3.
Macrophages play an essential role in the immune system by ingesting and degrading invading pathogens, initiating an inflammatory response and instructing adaptive immune cells, and resolving inflammation to restore homeostasis. More interesting is the fact that some bacteria have evolved to use macrophages as a natural habitat and tools of spread in the host, e.g., Mycobacterium tuberculosis (Mtb) and some non-tuberculous mycobacteria (NTM). Mtb is considered one of humanity’s most successful pathogens and is the causal agent of tuberculosis, while NTMs cause opportunistic infections all of which are of significant public health concern. Here, we describe mechanisms by which intracellular pathogens, with an emphasis on mycobacteria, manipulate macrophage functions to circumvent killing and live inside these cells even under considerable immunological pressure. Such macrophage functions include the selective evasion or engagement of pattern recognition receptors, production of cytokines, reactive oxygen and nitrogen species, phagosome maturation, as well as other killing mechanisms like autophagy and cell death. A clear understanding of host responses elicited by a specific pathogen and strategies employed by the microbe to evade or exploit these is of significant importance for the development of effective vaccines and targeted immunotherapy against persistent intracellular infections like tuberculosis. 相似文献
4.
L. Adorini 《Cellular and molecular life sciences : CMLS》1999,55(12):1610-1625
Interleukin 12 (IL-12) is a heterodimeric cytokine produced primarily by antigen-presenting cells (APCs) which plays a key
role in promoting type 1 T helper cell (Th1) responses. The powerful activity of IL-12 requires tight control, which is exerted
at various levels. Primary control is exerted on IL-12 production by APCs, a major factor driving the response towards the
Th1 or Th2 phenotype. Another level of control regulates expression of the IL-12 receptor (IL-12R), which is composed of two
subunits, β1 and β2. The IL-12R β2 subunit has signal-transducing capacity and modulation of its expression is central to
the regulation of IL-12 responsiveness. Endogenous IL-12 plays an important role in host defense against infection by a variety
of intracellular pathogens. Its Th1-promoting activity, however, also favors Th1-mediated immunopathology and, in particular,
the induction of Th1-mediated autoimmune diseases.
Received 15 January 1999; received after revision 11 March 1999; accepted 16 March 1999 相似文献
5.
Intestinal epithelial barrier and mucosal immunity 总被引:12,自引:0,他引:12
Müller CA Autenrieth IB Peschel A 《Cellular and molecular life sciences : CMLS》2005,62(12):1297-1307
The innate immune system plays a crucial role in maintaining the integrity of the intestine and protecting the host against a vast number of potential microbial pathogens from resident and transient gut microflora. Mucosal epithelial cells and Paneth cells produce a variety of antimicrobial peptides (defensins, cathelicidins, crytdinrelated sequence peptides, bactericidal/permeabilityincreasing protein, chemokine CCL20) and bacteriolytic enzymes (lysozyme, group IIA phospholipase A2) that protect mucosal surfaces and crypts containing intestinal stem cells against invading microbes. Many of the intestinal antimicrobial molecules have additional roles of attracting leukocytes, alarming the adaptive immune system or neutralizing proinflammatory bacterial molecules. Dysfunction of components of the innate immune system has recently been implicated in chronic inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, illustrating the pivotal role of innate immunity in maintaining the delicate balance between immune tolerance and immune response in the gut. 相似文献
6.
Janesh Pillay Tamar Tak Vera M. Kamp Leo Koenderman 《Cellular and molecular life sciences : CMLS》2013,70(20):3813-3827
Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cells (G-MDSCs). In this review, we will discuss the similarities and differences between neutrophils and G-MDSCs. Various types of G-MDSCs have been described, ranging from immature to mature cells shaping the immune response by different immune suppressive mechanisms. However, all types of G-MDSCs share distinct features of neutrophils, such as surface markers and morphology. We propose that G-MDSCs are heterogeneous and represent novel phenotypes of neutrophils, capable of suppressing the immune response. In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research. 相似文献
7.
U Certa 《Experientia》1991,47(2):157-163
Among infectious diseases caused by protozoa, malaria is still the greatest killer of children. Mortality in adults living in endemic areas is significantly lower because they frequently acquire partial or complete immunity to the major pathogen, Plasmodium falciparum. This natural protection indicates that vaccination may be possible, and the first candidate antigens were cloned with the use of human immune sera as probes. Genetic and biochemical analysis of the parasite proteins revealed that they are polymorphic, and frequently gene sequences were discovered which were specific for a particular parasite isolate, which eliminated most antigens for purposes of vaccine development. The most promising candidate antigens today are the major surface proteins of sporozoites and blood stage parasites. However, the immune response against those is not sufficient for complete protection, and additional, intensive research is necessary to identify new molecules to be included in a vaccine cocktail against malaria. The current spread of the disease due to increasing drug resistance of parasites and mosquito vectors emphasizes the urgent need for a vaccine. 相似文献
8.
Yusuke Endo Koutaro Yokote Toshinori Nakayama 《Cellular and molecular life sciences : CMLS》2017,74(7):1231-1245
Chronic inflammation associated with obesity plays a major role in the development of metabolic diseases, cancer, and autoimmune diseases. Among Th subsets, Th17 cells are involved in the pathogenesis of autoimmune disorders such as psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Accumulating data suggest that reciprocal interactions between the metabolic systems and immune system play pivotal roles in the pathogenesis of obesity-associated diseases. We herein outline the developing principles in the control of T cell differentiation and function via their cellular metabolism. Also discussed are recent findings that changes in the intracellular metabolism, including fatty acid metabolism, affect the Th17 cell function in obese individuals. Finally, we will also highlight the unique molecular mechanism involved in the activation of retinoid-related orphan receptor-gamma-t (RORγt) by intracellular metabolism and discuss a new therapeutic approach for treating autoimmune disorders through the inhibition of RORγt. 相似文献
9.
Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines 总被引:2,自引:0,他引:2
Carralot JP Probst J Hoerr I Scheel B Teufel R Jung G Rammensee HG Pascolo S 《Cellular and molecular life sciences : CMLS》2004,61(18):2418-2424
In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based
vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to
any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled
expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies).
We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for
-galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy
primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application
of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the
administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the
requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004 相似文献
10.
The skin is a highly accessible organ and constitutes an active immunological site. Both these properties make this surface an attractive route for what promises to be a cost-effective, simple, practical and needle-free delivery of vaccines and immunomodulators. Less obvious is the fact that the state of the skin barrier can influence quantitative and qualitative aspects of antigen-specific immune responses. The everyday decision-making at the skin epithelium concerns the choice between the induction of an immune response and the establishment of a state of non-responsiveness (tolerance). This decision is influenced by various factors such as the dose, the route (intact vs barrier-disrupted skin), the cytokine microenvironment and the nature of the antigenic stimulus. By increasing our understanding of how immune responses are regulated in the epidermis we can envisage the development of immunisation protocols aimed at eliciting a protective immune response or inducing tolerance, with direct applications to preventive or therapeutic vaccination, respectively.Received 29 November 2004; received after revision 2 February 2005; accepted 22 February 2005 相似文献
11.
The maintenance of mucosal barrier equilibrium in the intestine requires a delicate and dynamic balance between enterocyte
loss by apoptosis and the generation of new cells by proliferation from stem cell precursors at the base of the intestinal
crypts. When the balance shifts towards either excessive or insufficient apoptosis, a broad range of gastrointestinal diseases
can manifest. Recent work from a variety of laboratories has provided evidence in support of a role for receptors of the innate
immune system, including Toll-like receptors 2, 4, and 9 as well as the intracellular pathogen recognition receptor NOD2/CARD15,
in the initiation of enterocyte apoptosis. The subsequent induction of enterocyte apoptosis in response to the activation
of these innate immune receptors plays a key role in the development of various intestinal diseases, including necrotizing
enterocolitis, Crohn’s disease, ulcerative colitis, and intestinal cancer. This review will detail the regulatory pathways
that govern enterocyte apoptosis, and will explore the role of the innate immune system in the induction of enterocyte apoptosis
in gastrointestinal disease. 相似文献
12.
Dawn M. Walker Steve Oghumu Gaurav Gupta Bradford S. McGwire Mark E. Drew Abhay R. Satoskar 《Cellular and molecular life sciences : CMLS》2014,71(7):1245-1263
Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality. 相似文献
13.
Morgan Grau Paul R. Walker Madiha Derouazi 《Cellular and molecular life sciences : CMLS》2018,75(16):2887-2896
Immunotherapies are increasingly used to treat cancer, with some outstanding results. Immunotherapy modalities include therapeutic vaccination to eliminate cancer cells through the activation of patient’s immune system against tumor-derived antigens. Nevertheless, the full potential of therapeutic vaccination has yet to be demonstrated clinically because many early generation vaccines elicited low-level immune responses targeting only few tumor antigens. Cell penetrating peptides (CPPs) are highly promising tools to advance the field towards clinical success. CPPs efficiently penetrate cell membranes, even when linked to antigenic cargos, which can induce both CD8 and CD4 T-cell responses. Pre-clinical studies demonstrated that targeting multiple tumor antigens, even those considered to be poorly immunogenic, led to tumor regression. Therefore, CPP-based cancer vaccines represent a flexible and powerful means to extend therapeutic vaccination to many cancer indications. Here, we review recent findings in CPP development and discuss their use in next generation immunotherapies. 相似文献
14.
Immunological memory allows for rapid and effective protective immunity to previously encountered pathogens. New insights in understanding specific memory differentiation and function have now indicated that in addition to providing enhanced immunity, an important purpose of immunological memory is to provide immediate protection at all sites of the body, including non-lymphoid tissues. Effector memory CD8 T cells have the capacity to reside long-term at epithelial surfaces, where they allow for rapid containment of the invading pathogens at the local entry site and prevent systemic spreading and excessive immune responses. The accumulation of tissue-specific memory T cell subsets, together with cross-reactivity of these antigen-experienced T cells even to unrelated pathogens, provides flexibility and expansion of their specificity repertoire that over time greatly surpasses that of the declining na?ve T cell populations. This review will discuss new insights into T cell memory. We will focus in particular on the generation and function of effector memory CD8 T cells at the intestinal mucosa, which represents one of the largest entry sites for pathogens. 相似文献
15.
Rosenstiel P Jacobs G Till A Schreiber S 《Cellular and molecular life sciences : CMLS》2008,65(9):1361-1377
NOD-like receptors (NLRs) comprise a family of cytosolic proteins that have been implicated as ancient cellular sentinels
mediating protective immune responses elicited by intracellular pathogens or endogenous danger signals. Genetic variants in
NLR genes have been associated with complex chronic inflammatory barrier diseases (e.g. Crohn disease, bronchial asthma). In
this review, we focus on the molecular pathophysiology of NLRs in the context of chronic inflammatory diseases and pinpoint
recent advances in the evolutionary understanding of NLR biology. We propose that the field of NLRs may serve as a prototype
for how a comprehensive understanding of an element of the immunological barrier will eventually lead to the development of
targeted diagnostic, therapeutic and/or preventive strategies.
Received 29 October 2007; received after revision 10 December 2007; accepted 19 December 2007 相似文献
16.
Current cases in which epitope mimicry is considered as a component cause of autoimmune disease: immune-mediated (type 1) diabetes 总被引:2,自引:0,他引:2
Autoimmune diseases result from a combination of genetic, immunologic, hormonal, and environmental factors. Infectious agents may induce the breakdown of immunological tolerance and the appearance of autoreactivity. However, the specific relationship between infection and autoimmunity is still unclear. One of the mechanisms responsible could be molecular mimicry between the infectious agent and self. The concept of molecular mimicry is a viable hypothesis in the investigation of the etiology, pathogenesis, treatment, and prevention of autoimmune disorders. Immune-mediated (type 1) diabetes in humans and in non-obese diabetic (NOD) mice is polygenic and characterized by autoimmune destruction of insulin-producing pancreatic beta cells in islets of Langerhans. In NOD mice, a T-helper 1 (Th1)-based autoimmune response arises spontaneously against glutamate decarboxylase (GAD) concurrently with the onset of insulitis. Subsequently. this Th1-type autoreactivity spreads intra- and intermolecularly to other beta cell autoantigens, suggesting that a Th1-type response is responsible for the progression of the disease, whereas Th2 responses when experimentally induced are protective. In humans, a homology between GAD and the P2-C protein of Coxsackie B make a cause-and-effect molecular mimicry an attractive hypothesis. Evidence to support the concept of molecular mimicry in diabetes is reviewed. 相似文献
17.
de Wit PJ 《Cellular and molecular life sciences : CMLS》2007,64(21):2726-2732
Plants have an innate immunity system to defend themselves against pathogens. With the primary immune system, plants recognize
microbe-associated molecular patterns (MAMPs) of potential pathogens through pattern recognition receptors (PRRs) that mediate
a basal defense response. Plant pathogens suppress this basal defense response by means of effectors that enable them to cause
disease. With the secondary immune system, plants have gained the ability to recognize effector-induced perturbations of host
targets through resistance proteins (RPs) that mediate a strong local defense response that stops pathogen growth. Both primary
and secondary immune responses in plants depend on germ line-encoded PRRs and RPs. During induction of local immune responses,
systemic immune responses also become activated, which predispose plants to become more resistant to subsequent pathogen attacks.
This review gives an update on recent findings that have enhanced our understanding of plant innate immunity and the arms
race between plants and their pathogens.
Received 24 June 2007; received after revision 18 July 2007; accepted 15 August 2007 相似文献
18.
Research over the last several years has greatly advanced our understanding of the mechanisms by which the immune system functions. There exist two main branches of immunity, termed innate and adaptive immunity. Innate immunity uses the genetic memory of germline-encoded receptors to recognize the molecular patterns of common pathogens. Adaptive immunity, akin to somatic memory, is a complex system by which the body learns to recognize a pathogens unique antigens and builds an antigen specific response to destroy it. The effective development of the overall immune response depends on careful interplay and regulation between innate and adaptive immunity. Here we review our current understanding of how these integrated systems distinguish targets against which a response is appropriate and neutralize potentially pathogenic challenges.Received 8 May 2003; accepted 2 June 2003 相似文献
19.
Temporins, anti-infective peptides with expanding properties 总被引:2,自引:1,他引:1
Mangoni ML 《Cellular and molecular life sciences : CMLS》2006,63(9):1060-1069
Antimicrobial peptides are effector molecules of the innate immune response of all pluricellular organisms, providing them
with first-line defence against pathogens. Amphibian skin secretions represent one of the richest natural sources for such
peptide antibiotics, and temporins, a large family of antimicrobial peptides from frog skin, are among the smallest ones found
in nature to date. Their functional role and modes of action have been described, along with their interesting and unique
properties. These properties make temporins good molecules for an in-depth understanding of host defence peptides in general.
Furthermore, they are attractive templates for the future design of new therapeutics against infectious diseases with new
modes of action, urgently needed due to the increasing resistance of microorganisms to the available drugs.
Received 8 November 2005; received after revision 19 December 2005; accepted 18 January 2006 相似文献