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Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background, clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is currently an urgent public health problem as high morbidity from the virus leaves populations with negative physical, social, and economic impacts. CHIKV has the potential to affect every organ of an individual, leaving patients with lifelong impairments which negatively affect their quality of life. In this review, we show the importance of CHIKV in research and public health by demonstrating the immunopathology of CHIKV as it presents in different organ systems. Papers used in this review were found on PubMed, using "chikungunya and [relevant organ system]". There is a significant inflammatory response during CHIKV infection which affects several organ systems, such as the brain, heart, lungs, kidneys, skin, and joints, and the immune response to CHIKV in each organ system is unique. Whilst there is clinical evidence to suggest that serious complications can occur, there is ultimately a lack of understanding of how CHIKV can affect different organ systems. It is important for clinicians to understand the risks to their patients. [ABSTRACT FROM AUTHOR]

Amphibians are currently the most threatened vertebrate class, with the disease chytridiomycosis being amajor contributor to their global declines. Chytridiomycosis is a frequently fatal skin disease caused by the fungal pathogens Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal). The severity and extent of the impact of the infection caused by these pathogens a cross modern Amphibia are unprecedented in the history of vertebrate infectious diseases. The immune systemof amphibians is thought to be largely similar to that of other jawed vertebrates, such asmammals. However, amphibian hosts are both ectothermic and water-dependent, which are characteristics favouring fungal proliferation. Although amphibians possess robust constitutive host defences, Bd/Bsal replicate within host cells once these defences have been breached. Intracellular fungal localisation may contribute to evasion of the induced innate immune response. Increasing evidence suggests that once the innate defences are surpassed, fungal virulence factors suppress the targeted adaptive immune responses whilst promoting an ineffectual inflammatory cascade, resulting in immunopathology and systemic metabolic disruption. Thus, although infections are contained within the integument, crucial homeostatic processes become compromised, leading to mortality. In this paper, we present an integrated synthesis of amphibian post-metamorphic immunological responses and the corresponding outcomes of infection with Bd, focusing on recent developments within the field and highlighting future directions. [ABSTRACT FROM AUTHOR]

• AM have roles in SM induced pulmonary injury • AM polarization skews SM-induced pathology • AM targeting is a potential treatment for SM toxicity Despite many studies investigating the mechanism of Sulfur Mustard (SM) induced lung injury, the underlying mechanism is still unclear. Inflammatory and subsequent fibroproliferative stages of SM-toxicity are based upon several highly-related series of events controlled by the immune system. The inhalation of SM gas variably affects different cell populations within the lungs. Various studies have shown the critical role of macrophages in triggering a pulmonary inflammatory response as well as its maintenance, resolution, and repair. Importantly, macrophages can serve as either pro-inflammatory or anti-inflammatory populations depending on the present conditions at any pathological stage. Different characteristics of macrophages, including their differentiation, phenotypic, and functional properties, as well as interactions with other cell populations determine the outcomes of lung diseases and the extent of long- or short-term pulmonary damage induced by SM. In this paper, we summarize the current state of knowledge regarding the role of alveolar macrophages and their mediators in the pathogenesis of SM in pulmonary injury. Investigating the specific cells and mechanisms involved in SM-lung injury may be useful in finding new target opportunities for treatment of this injury. [ABSTRACT FROM AUTHOR]

An allergy is commonly understood to be an overreaction of the immune system to harmless substances that are misrecognised as foreign. This concept of allergy as an abnormal, misdirected immune response—a biological fault—stems from the idea that the immune system is an inherently defensive operation designed to protect the individual through an innate capacity to discriminate between the benign and toxic, or self and nonself. However, this definition of allergy represents a radical departure from its original formulation. Literally meaning ‘altered reactivity’, the term was coined in 1906 by Austrian paediatrician Clemens von Pirquet, to describe the fundamentally mutable nature of the immune response. This paper argues that the conventional interpretation of allergy-as-pathology derives from specific concepts of ‘organism’, ‘response’, and ‘normal’ immune function that have—for over a century—governed the perception and study of immune phenomena within immunology. Through an examination of Louis Pasteur’s conceptualisation of the host body/microorganism relationship, I argue that immunology is founded on a view of the organism as a discrete, autonomous entity, and on a concomitant notion of the immune response as essentially reactive. Revisiting the concept of ‘altered reactivity’, this paper points to the fact that allergy was initially posited as a general theory of immune responsiveness and, importantly, one that poses a significant challenge to orthodox notions of immunopathology. It suggests that Pirquet’s unique view of immune responsiveness presents an account of organismic or biological identity that encapsulates, rather than reduces, its ecological complexity. [Copyright &y& Elsevier]

Background: Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods: C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER) or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsastained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10) were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results: P. chabaudi (ER) infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the response of CD4 T cells producing IFN-γ and IL-4. Conclusion: The data in this paper suggest that studying early host responses in blood stage malaria infections measured after direct blood challenge of mice may not completely reflect the natural situation, and more detailed investigations of blood-stage immunity after mosquito transmission in experimental models should be considered. [ABSTRACT FROM AUTHOR]

The present issue of Seminars in Immunopathology is motivated by the fact that the diseases of poverty, HIV/AIDS, tuberculosis and malaria, and the neglected tropical diseases (NTDs; [[1]]) still represent the major burden of ill health in tropical and subtropical areas, particularly in the low- and middle-income countries. This key question is elegantly developed further by the paper of Kaye et al. [[5]] that examines the complexity of the immune responses and immunopathology in leishmaniosis with regard to the impact on the development of vaccines and also diagnostics. It is this very insight - combined with decade-long experience - that guides us towards the priority avenues for R&D. The paper of Brazier et al. [[8]] provides the promising outlook for the development of new vaccines against I Mycobacterium tuberculosis i by assessing the realistic targets for any vaccine development. [Extracted from the article]

The article presents research papers related to medical sciences. One of the paper "Discrepancies in Immunology: Immunoprotection Immunopathology-Autoimmunity?" by R. Zinkemagel discusses the autoimmune process of human body. The paper "Gene Expression Profiling of the Nonhuman Primate Hypothalamus at the Time of Female Puberty Reveals Activation of Tumor Suppressor Gene Expression," by C.L. Roth, C. Mastronardi, A. Mungenast, S. Heger, H. Jung and S.R. Ojeda evaluates the hypothalamus of peripubertal female rhesus monkeys via cDNA arrays.

Hansen's disease is manifested in a broad spectrum: clinical and histopathological. These differences arise from an individual's immunological response against diverse components of Mycobacterium leprae. Leprosy constitutes a study model of immunity response, where leprosy reaction type 1 can develop in an increased reaction; in that case, it is called a reverse reaction, or can develop in a withering of the response, which is then called a degrading response. These variations correspond to the instability of the cell immune response. Leprosy reaction 2 differs in that it is produced under appeasement of humoral type of immune response. Leprosy reaction type 1, in reversal variety, is expressed clinically as an inflammatory exacerbation of skin lesions and nervous trunks, with motor and sensitive alterations. This type of reaction is present in the dimorph varieties of Hansen's disease. The recognition of the reactional states is essential to give an early and efficient treatment and to avoid the appearance of the stigmatas of the disease. This paper describes clinical aspects through the presentation of a case and reviews its immunology, epidemiology, histopathology and treatment. [ABSTRACT FROM AUTHOR]

TIPE2, the tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2), plays an essential role in maintaining immune homeostasis. It is highly expressed in macrophages and negatively regulates inflammation through inhibiting Toll-like receptor signaling. In this paper, we utilized RAW264.7 cells stably transfected with a TIPE2 expression plasmid, as well as TIPE2-deficient macrophages to study the roles of TIPE2 in LPS-induced nitric oxide (NO) and urea production. The results showed that TIPE2-deficiency significantly upregulated the levels of iNOS expression and NO production in LPS-stimulated macrophages, but decreased mRNA levels of arginase I and urea production. However, TIPE2 overexpression in macrophages was capable of downregulating protein levels of LPS-induced iNOS and NO, but generated greater levels of arginase I and urea production. Furthermore, TIPE2−/− mice had higher iNOS protein levels in lung and liver and higher plasma NO concentrations, but lower levels of liver arginase I compared to LPS-treated WT controls. Interestingly, significant increases in IκB degradation and phosphorylation of JNK, p38, and IκB were observed in TIPE2-deficient macrophages following LPS challenge. These results strongly suggest that TIPE2 plays an important role in shifting L-arginase metabolism from production of NO to urea, during host inflammatory response. [ABSTRACT FROM AUTHOR]

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and affects ca. 10 million people worldwide. About 30% of Chagas disease patients develop chronic Chagas disease cardiomyopathy (CCC), a particularly lethal inflammatory cardiomyopathy that occurs decades after the initial infection, while most patients remain asymptomatic. Mortality rate is higher than that of noninflammatory cardiomyopathy. CCC heart lesions present a Th1 T-cell-rich myocarditis, with cardiomyocyte hypertrophy and prominent fibrosis. Data suggest that the myocarditis plays a major pathogenetic role in disease progression. Major unmet goals include the thorough understanding of disease pathogenesis and therapeutic targets and identification of prognostic genetic factors. Chagas disease thus remains a neglected disease, with no vaccines or antiparasitic drugs proven efficient in chronically infected adults, when most patients are diagnosed. Both familial aggregation of CCC cases and the fact that only 30%of infected patients develop CCC suggest there might be a genetic component to disease susceptibility.Moreover, previous case-control studies have identified some genes associated to human susceptibility to CCC. In this paper,wewill reviewthe immunopathogenesis and genetics of Chagas disease, highlighting studies that shed light on the differential progression of Chagas disease patients to CCC. [ABSTRACT FROM AUTHOR]

Abstract: Immunology is a relatively new specialty. Ironically, the immune system impacts every physiological system in the body, but yet most textbooks of physiology do not include any functional aspects of the immune system. Indeed, with the exception of early descriptions of anaphylaxis and allergy, the majority of immune studies were focused on either the anatomy of lymph nodes and spleen, or of course on protection from microorganisms. The concept of autoimmunity is even newer and the first textbook on autoimmune disease was not published until 1963. For the past 50 years however, autoimmunity has virtually exploded from a field populated by a few, to recognition that autoimmune diseases can affect more than 10% of the population. There are many people that have contributed to this information explosion and the Journal of Autoimmunity devotes specific issues in recognition of the select few scientists that have contributed in a way that impacts not only their research peers, but also, and more importantly, the patients who suffer from autoimmune disease. Abul Abbas is one such individual. Abul is known not only for his outstanding research, but for his role in teaching and public service. His own scientific work is extraordinary and his impact is felt throughout the world. In this special issue a number of Abul's colleagues have specifically written papers to honor this unique individual. It is an extraordinary honor to be chosen for a special issue of a journal in recognition of one's career. [Copyright &y& Elsevier]

Background: The emergence of drug-resistant pathogen strains and new infectious agents pose major challenges to public health. A promising approach to combat these problems is to target the host’s genes or proteins, especially to discover targets that are effective against multiple pathogens, i.e., host-oriented broad-spectrum (HOBS) drug targets. An important first step in the discovery of such drug targets is the identification of host responses that are commonly perturbed by multiple pathogens. Results: In this paper, we present a methodology to identify common host responses elicited by multiple pathogens. First, we identified host responses perturbed by each pathogen using a gene set enrichment analysis of publicly available genome-wide transcriptional datasets. Then, we used biclustering to identify groups of host pathways and biological processes that were perturbed only by a subset of the analyzed pathogens. Finally, we tested the enrichment of each bicluster in human genes that are known drug targets, on the basis of which we elicited putative HOBS targets for specific groups of bacterial pathogens. We identified 84 up-regulated and three down-regulated statistically significant biclusters. Each bicluster contained a group of pathogens that commonly dysregulated a group of biological processes. We validated our approach by checking whether these biclusters correspond to known hallmarks of bacterial infection. Indeed, these biclusters contained biological process such as inflammation, activation of dendritic cells, pro- and anti- apoptotic responses and other innate immune responses. Next, we identified biclusters containing pathogens that infected the same tissue. After a literature-based analysis of the drug targets contained in these biclusters, we suggested new uses of the drugs Anakinra, Etanercept, and Infliximab for gastrointestinal pathogens Yersinia enterocolitica, Helicobacter pylori kx2 strain, and enterohemorrhagic Escherichia coli and the drug Simvastatin for hematopoietic pathogen Ehrlichia chaffeensis. Conclusions: Using a combination of automated analysis of host-response gene expression data and manual study of the literature, we have been able to suggest host-oriented treatments for specific bacterial infections. The analyses and suggestions made in this study may be utilized to generate concrete hypothesis on which gene sets to probe further in the quest for HOBS drug targets for bacterial infections. All our results are available at the following supplementary website: http://bioinformatics.cs.vt.edu/ murali/supplements/2013-kidane-plos-one [ABSTRACT FROM AUTHOR]

c-Rel plays important roles in many inflammatory diseases. Revealing the dynamic expression of c-Rel in disease processes in vivo is critical for understanding c-Rel functions and for developing anti-inflammatory drugs. In this paper, a transgenic mouse line, B6-Tg(c-Rel-luc)Mlit, which incorporated the transgene firefly luciferase driven by a 14.5-kb fragment containing mouse c-Rel gene Rel promoter, was generated to monitor Rel expression in vivo. Luciferase expression could be tracked in living mice by the method of bioluminescence imaging in a variety of inflammatory processes, including LPS induced sepsis and EAE disease model. The luciferase expression in transgenic mice was comparable to the endogenous Rel expression and could be suppressed by administration of anti-inflammatory drug dexamethasone or aspirin. These results indicate that the B6-Tg(c-Rel-luc)Mlit mouse is a valuable animal model to study Rel expression in physiological and pathological processes, and the effects of various drug treatments in vivo. [ABSTRACT FROM AUTHOR]

Background: Previous work has shown that disruption of the gene for group X secreted phospholipase A2 (sPLA2-X) markedly diminishes airway hyperresponsiveness and remodeling in a mouse asthma model. With the large number of additional sPLA2s in the mammalian genome, the involvement of other sPLA2s in the asthma model is possible – in particular, the group V sPLA2 (sPLA2-V) that like sPLA2-X is highly active at hydrolyzing membranes of mammalian cells. Methodology and Principal Findings: The allergen-driven asthma phenotype was significantly reduced in sPLA2-V-deficient mice but to a lesser extent than observed previously in sPLA2-X-deficient mice. The most striking difference observed between the sPLA2-V and sPLA2-X knockouts was the significant impairment of the primary immune response to the allergen ovalbumin (OVA) in the sPLA2-V−/− mice. The impairment in eicosanoid generation and dendritic cell activation in sPLA2-V−/− mice diminishes Th2 cytokine responses in the airways. Conclusions: This paper illustrates the diverse roles of sPLA2s in the immunopathogenesis of the asthma phenotype and directs attention to developing specific inhibitors of sPLA2-V as a potential new therapy to treat asthma and other allergic disorders. [ABSTRACT FROM AUTHOR]

Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vectors. This will depend largely on updated knowledge of relevant and fundamental parasite biology. There is a need, therefore, to exploit and apply new knowledge and techniques in order to make significant and novel gains in combating helminthiases and supporting the sustainability of current and successful mass drug administration (MDA) programmes. Among the fields of basic research that are likely to yield improved control tools, the Disease Reference Group on Helminth Infections (DRG4) has identified four broad areas that stand out as central to the development of the next generation of helminth control measures: 1) parasite genetics, genomics, and functional genomics; 2) parasite immunology; 3) (vertebrate) host-parasite interactions and immunopathology; and 4) (invertebrate) host-parasite interactions and transmission biology. The DRG4 was established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR). The Group was given the mandate to undertake a comprehensive review of recent advances in helminthiases research in order to identify notable gaps and highlight priority areas. This paper summarises recent advances and discusses challenges in the investigation of the fundamental biology of those helminth parasites under the DRG4 Group's remit according to the identified priorities, and presents a research and development agenda for basic parasite research and enabling technologies that will help support control and elimination efforts against human helminthiases. [ABSTRACT FROM AUTHOR]

In recent years, there has been an increased recognition that vitamin D is not only a risk factor for poor musculoskeletal health but also a possible important contributor in the development of different autoimmune diseases. This has been linked to multiple immunosuppressive properties of vitamin D. Vitamin D has got pleiotropic effects and this reflects the wide spread presence of vitamin D receptors (VDRs) throughout the body. Currently, there is much ongoing research with regard to its emerging role in immunopathology. VDR has not only been found in tissues involved in calcium homeostasis but also in a variety of cell lines involved primarily in immune regulation, e.g., mononuclear cells, dendritic cells, antigen-presenting cells, and activated B lymphocytes and CD4+ T cells. There have been several reports linking the presence of low vitamin D to various autoimmune diseases. However, for autoimmune/inflammatory disease outcomes, firm conclusions regarding cause and effect cannot be based on epidemiological association studies, and prospective, long-term, well-designed studies, including large intervention trials, are needed across all life stages. In this paper, we will describe the evidence base for this potential role of vitamin D in different aspects of autoimmune diseases. Because of the enormous breadth of this emerging field, our aim in this review is not to provide an exhaustive list of all literature pertinent to vitamin D and immunopathology. Instead, we will frame the reasons and rationale behind the development of several immunoregulatory activities for 1,25(OH)2D3. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common autoimmune disease and a systemic inflammatory disease which is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion and hyperplasia of synovial tissues. Considering the role of autoreactive T cells (particularly Th1 and Th17 cells) in pathophysiology of RA, it might be assumed that the regulatory T cells (Tregs) will be able to control the initiation and progression of disease. The frequency, function, and properties of various subsets of Tregs including natural Tregs (nTregs), IL-10-producing type 1 Tregs (Tr1 cells), TGF-β-producing Th3 cells, CD8+ Tregs, and NKT regulatory cells have been investigated in various studies associated with RA and collagen-induced arthritis (CIA) as experimental model of this disease. In this paper, we intend to submit the comprehensive information about the immunobiology of various subsets of Tregs and their roles and function in immunopathophysiology of RA and its animal model, CIA. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic, autoimmune, and complex inflammatory disease leading to bone and cartilage destruction, whose cause remains obscure. Accumulation of genetic susceptibility, environmental factors, and dysregulated immune responses are necessary for mounting this self-reacting disease. Inflamed joints are infiltrated by a heterogeneous population of cellular and solublemediators of the immune system, such as T cells, B cells, macrophages, cytokines, and prostaglandins (PGs). Prostaglandins are lipid inflammatory mediators derived from the arachidonic acid by multienzymatic reactions. They both sustain homeostatic mechanisms and mediate pathogenic processes, including the inflammatory reaction. They play both beneficial and harmful roles during inflammation, according to their site of action and the etiology of the inflammatory response. With respect to the role of PGs in inflammation, they can be effective mediators in the pathophysiology of RA. Thus the use of agonists or antagonists of PG receptors may be considered as a new therapeutic protocol in RA. In this paper, we try to elucidate the role of PGs in the immunopathology of RA. [ABSTRACT FROM AUTHOR]

Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the genera Rickettsia, Orientia, Ehrlichia, and Anaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecular Rickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, andmodulation of gene expression. The roles of innate and adaptive immune responses are discussed, and potential new targets for therapies to block host-pathogen interactions and pathogen virulence mechanisms are considered. [ABSTRACT FROM AUTHOR]

Dermatitis herpetiformis (DH) is an inflammatory cutaneous disease with typical histopathological and immunopathological findings clinically characterized by intensely pruritic polymorphic lesions with a chronic-relapsing course. In addition to classic clinical manifestations of DH, atypical variants are more and more frequently reported and histological and immunological are added to them, whereas the impact on quality of life of patients with DH is increasingly important to a certain diagnosis. The aim of this paper is to describe all the possible clinical, histological, and immunological variants of DH in order to facilitate the diagnosis of a rare disease and, therefore, little known. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology affecting more than onemillion individuals each year. It is characterized by B- and T-cell hyperactivity and by defects in the clearance of apoptotic cells and immune complexes. Understanding the complex process involved and the interaction between various cytokines, chemokines, signaling molecules, and pattern-recognition receptors (PRRs) in the immune pathways will provide valuable information on the development of novel therapeutic targets for treating SLE. In this paper, we review the immunopathological roles of novel cytokines, chemokines, signaling molecules, PRRs, and their interactions in immunoregulatory networks and suggest how their disturbances may implicate pathological conditions in SLE. [ABSTRACT FROM AUTHOR]

Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) are amongst the most common human infectious viral pathogens capable of causing serious clinical diseases at every stage of life, from fatal disseminated disease in newborns to cold sores genital ulcerations and blinding eye disease. Primary mucocutaneous infection with HSV-1 & HSV-2 is followed by a lifelong viral latency in the sensory ganglia. In themajority of cases, herpes infections are clinically asymptomatic.However, in symptomatic individuals, the latentHSV can spontaneously and frequently reactivate, reinfecting themuco-cutaneous surfaces and causing painful recurrent diseases. The innate and adaptive mucosal immunities to herpes infections and disease remain to be fully characterized. The understanding of innate and adaptive immune mechanisms operating at muco-cutaneous surfaces is fundamental to the design of next-generation herpes vaccines. In this paper, the phenotypic and functional properties of innate and adaptive mucosal immune cells, their role in antiherpes immunity, and immunopathology are reviewed. The progress and limitations in developing a safe and efficient mucosal herpes vaccine are discussed [ABSTRACT FROM AUTHOR]

Our understanding of tuberculosis (TB) pathology and immunology has become extensively deeper and more refined since the identification of Mycobacterium tuberculosis (MTB) as the etiologic agent of disease by Dr. Robert Koch in 1882. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. TB, caused by MTB, is a major health problem in world, with 10 million new cases diagnosed each year. Innate immunity is shown playing an important role in the host defense against the MTB, and the first step in this process is recognition of MTB by cells of the innate immune system. Several classes of pattern recognition receptors (PPRs) are involved in the recognition of MTB, including toll-like receptors (TLRs), C-type lectin receptors (CLRs), and nod-like receptors (NLRs). Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down streams, proteins play the most prominent roles in the initiation of the immune response against MTB. Beside of TLRs signaling, recently the activation of inflammasome pathway in the pathogenesis of TB much appreciated. Knowledge about these signaling pathways is crucial for understanding the pathophysiology of TB, on one hand, and for the development of novel strategies of vaccination and treatment such as immunotherapy on the other. Given the critical role of TLRs/inflammasome signaling in innate immunity and initiation of the appropriate adaptive response, the regulation of these pathways is likely to be an important determinant of the clinical outcome of MTB infection. In this review paper we focused on the immune response, which is the recognition of MTB by inflammatory innate immune cells following infection. [ABSTRACT FROM AUTHOR]

Water and foodborne enteric cryptosporidiosis is a globally emerging public health issue. Although the clinical manifestations of enteric cryptosporidiosis are generally limited to intestinal infection and subsequent diarrhoea, extra-intestinal invasion has also been diagnosed in immunocompromised individuals, particularly in those infected with human immunodeficiency virus (HIV) or AIDS. Due to an inadequate understanding of Cryptosporidium immunopathogenesis in humans, the development of vaccines or therapeutic agents and their application in diseases management is difficult. Current therapeutic measures are not fully effective in the treatment of the disease. Therefore, the implementation of strategies designed to control the chain of cryptosporidiosis transmission (environment ↔ human ↔ food/water ↔ animal) is a critical but challenging issue to public health authorities across the world. Several excellent studies have been done on innate, acquired and mucosal immunity against Cryptosporidium infections using animal models, in vitro human cell lines and human volunteers. However, there are still multiple challenges in understanding the intestinal immune response (immunopathogenesis) to Cryptosporidium infection in humans. This paper reviews recent updates on immunopathogenesis and immune responses to Cryptosporidium infection in humans, while also discussing the current limitations that exist regarding a precise understanding of the immunopathological mechanisms. [ABSTRACT FROM AUTHOR]

Immunopathology is a major cause of influenza-associated morbidity and mortality worldwide. However, the role and regulatory mechanisms of CD4 T cells in severe lung immunopathology following acute influenza infection are poorly understood. In this paper, we report that the emergence of immunopathogenic CD4 T cells is under the control of a transmembrane immunoadaptor DAP12 pathway during influenza infection. We find that the mice lacking DAP12 have unaltered viral clearance but easily succumb to influenza infection as a result of uncontrolled immunopathology. Such immunopathology is associated with markedly increased CD4 T cells displaying markedly increased cytotoxicity and Fas ligand expression. Furthermore, the immunopathogenic property of these CD4 T cells is transferrable. Thus, depletion of CD4 T cells or abrogation of Fas/Fas ligand signaling pathway improves survival and immunopathology. We further find that DAP12 expressed by dendritic cells plays an important role in controlling the immunopathogenic CD4 T cells during influenza infection. Our findings identify a novel pathway that controls the level of immune-pathogenic CD4 T cells during acute influenza infection. [ABSTRACT FROM AUTHOR]

B cells regulate autoimmune pathologies and chronic inflammatory conditions such as autoimmune encephalomyelitis and inflammatory bowel disease. The potential counterregulatory role of B cells in balancing pathogen-specific immune responses and the associated immunopathology is less well understood owing to the lack of appropriate persistent infection models. In this paper, we show that B cells have the ability to negatively regulate adaptive immune responses to bacterial pathogens. Using mouse models of infection with Helicobacter felis, a close relative of the human gastrointestinal pathogen H. pylori, we found that B cells activated by Helicobacter TLR-2 ligands induce IL-10-producing CD4+CD25+ T regulatory-1 (Tr-1)-like cells in vitro and in vivo. Tr-1 conversion depends on TCR signaling and a direct T-/B-interaction through CD40/CD40L and CD80/CD28. B cell-induced Tr-1 cells acquire suppressive activity in vitro and suppress excessive gastric Helicobacter-associated immunopathology in vivo. Adoptive cotransfer of MyD88-proficient B cells and Tr-1 cells restores a normal gastric mucosal architecture in MyD88-/- and IL-10-/- mice in a manner that depends on T cellular, but not B cellular, IL-10 production. Our findings describe a novel mechanism of B cell-dependent Tr-1 cell generation and function in a clinically relevant disease model. In conclusion, we demonstrate that the B cell/Tr-1 cell axis is essential for balancing the control of Helicobacter infection with the prevention of excessive Th1-driven gastric immunopathology, promoting gastric mucosal homeostasis on the one hand and facilitating Helicobacter persistence on the other. [ABSTRACT FROM AUTHOR]

Abstract: Although the complement system is centrally involved in host defense, its overactivation or deregulation (e.g., due to inherent host genetic defects or due to pathogen subversion) may excessively amplify inflammation and contribute to immunopathology. Periodontitis is an oral infection-driven chronic inflammatory disease which exerts a systemic impact on health. This paper reviews evidence linking complement to periodontal inflammation and pathogenesis. Clinical and histological observations show a correlation between periodontal inflammatory activity and local complement activation. Certain genetic polymorphisms or deficiencies in specific complement components appear to predispose to increased susceptibility to periodontitis. Animal model studies and in vitro experiments indicate that periodontal bacteria can either inhibit or activate distinct components of the complement cascade. Porphyromonas gingivalis, a keystone species in periodontitis, subverts complement receptor 3 and C5a anaphylatoxin receptor signaling in ways that promote its adaptive fitness in the presence of non-productive inflammation. Overall, available evidence suggests that complement activation or subversion contributes to periodontal pathogenesis, although not all complement pathways or functions are necessarily destructive. Effective complement-targeted therapeutic intervention in periodontitis would require determining the precise roles of the various inductive or effector complement pathways. This information is essential as it may reveal which specific pathways need to be blocked to counteract microbial evasion and inflammatory pathology or, conversely, kept intact to promote host immunity. [ABSTRACT FROM AUTHOR]

In light of understanding the Green House Effect, PCBs, Acid Rain, CFCs and the hole over the Ozone in the Antarctic. One can realize that these problems and issues are far beyond what we think. All these issues are a direct correlation with the introduction of the industrial revolution and the technologies implemented. This paper will look at some of the consequences for not implementing a sustainable system that is in harmony with our eco-system. This lays the foundation for engineers and scientists to see the need to develop sustainable systems that take into account the life cycle of their products and processes. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Moseley et al. (2010) Peroxisome proliferator-activated receptor and AMP-activated protein kinase agonists protect against lethal influenza virus challenge in mice. Influenza and Other Respiratory Viruses 4(5), 307–311. Background A novel influenza A (H1N1) virus was isolated from humans in North America and has developed into the first pandemic of the 21st century. Reports of a global shortage of antiviral drugs, the evolution of drug-resistant influenza virus variants, and a 6-month delay in vaccine availability underline the need to develop new therapeutics that may be widely distributed during future pandemics. Methods In an effort to discover alternatives to the conventional therapeutic strategies available, we screened several classes of immunomodulatory agents possessing the potential to mitigate the effects of influenza virus-induced immunopathology. Results Here, we provide preliminary evidence that two classes of drugs, peroxisome proliferator-activated receptor-γ agonists and AMP-activated protein kinase agonists, provide protection in mice infected with highly pathogenic and pandemic strains of influenza virus. Conclusions The extensive production in the developed world, combined with the significant degree of protection described here, establishes these drugs as a potential therapeutic option that may be broadly implemented to combat serious disease caused by future influenza epidemics or pandemics. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Functional characterization of T cells differentiated in vitro from bone marrow-derived CD34+ cells of psoriatic patients with family history. Experimental Dermatology 2010; 19: e128-e135. Abstract Background: The strong but complex genetic background suggests that inherent and intrinsic rather than exogenous factors have a key role in immunopathogenesis of psoriasis. It is reasonable to speculate that the dysfunctional activity of psoriatic T cells may partly originate from the abnormal haematopoietic cells. Objectives: To test if T cells originated from haematopoietic progenitor cells in psoriasis patients display functional alternations similar to previously reported abnormalities of circulating T cells. Methods: Bone marrow CD34+ haematopoietic cells were isolated from psoriatic patients with family history and healthy subjects, and differentiated into T cells in vitro in the thymic stromal co-culture system. These cells were further subjected to functional comparisons such as in vitro proliferation, secretion of cytokines such as IL-4, IL-8 and IFN-γ, and inducing the production of C-myc, Bcl-xL, and Ki67 proteins in human keratinocytes. Results: While bone marrow-derived CD34+ cells from both patients and healthy volunteers developed into mature T cells within weeks in the thymic environment in vitro, the differentiated T cells from psoriatic patients showed higher proliferation and stronger capacity to secret TH1 cytokines in response to streptococcal superantigen. The differentiated T cells from psoriatic patients, but not from normal controls, induced overexpression of C-myc and Ki67, but not Bcl-XL, in keratinocytes. Conclusions: T cells differentiated from CD34+ cells of psoriatic patients, but not normal controls, are functionally similar to psoriatic circulating T cells, suggesting that the dysfunctional activity of T cells in psoriatic patients can be traced back to the early development of haematopoietic cells. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) has traditionally been considered to be a T cell-mediated disease. However, there is an increasing body of evidence for the involvement of B cells and autoantibodies in the pathology of this disease, providing a rationale for treatment strategies directed against B cells. This paper summarizes the evidence for a key role of B cells in the immunopathology of MS and reviews data supporting the use of a novel B cell-targeted therapy, atacicept, for this condition. Atacicept is a human recombinant fusion protein that comprises the binding portion of a receptor for both BLyS (B Lymphocyte Stimulator) and APRIL (A PRoliferation-Inducing Ligand), two cytokines that have been identified as important regulators of B cell maturation, function and survival. Atacicept has shown selective effects on cells of the B cell lineage, acting on mature B cells and blocking plasma cells and late stages of B cell development while sparing B cell progenitors and memory cells. The efficacy of atacicept in animal models of autoimmune disease and the biological activity of atacicept in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) has been demonstrated. Ongoing clinical studies are investigating the safety, tolerability and efficacy of atacicept in patients with MS, SLE and RA. [ABSTRACT FROM AUTHOR]

The mechanisms operating in lymphocyte recruitment and homing to liver are reviewed. A literature review was performed on primary biliary cirrhosis (PBC), progressive sclerosing cholangitis (PSC), and homing mechanisms; a total of 130 papers were selected for discussion. Available data suggest that in addition to a specific role for CCL25 in PSC, the CC chemokines CCL21 and CCL28 and the CXC chemokines CXCL9 and CXCL10 are involved in the recruitment of T lymphocytes into the portal tract in PBC and PSC. Once entering the liver, lymphocytes localize to bile duct and retain by the combinatorial or sequential action of CXCL12, CXCL16, CX3CL1, and CCL28 and possibly CXCL9 and CXCL10. The relative importance of these chemokines in the recruitment or the retention of lymphocytes around the bile ducts remains unclear. The available data remain limited but underscore the importance of recruitment and homing. [ABSTRACT FROM AUTHOR]

Background: Regulatory T cells are central actors in the maintenance of tolerance of self-antigens or allergens and in the regulation of the intensity of the immune response during infections by pathogens. An understanding of the network of the interaction between regulatory T cells, antigen presenting cells and effector T cells is starting to emerge. Dynamical systems analysis can help to understand the dynamical properties of an interaction network and can shed light on the different tasks that can be accomplished by a network. Methodology and Principal Findings: We used a mathematical model to describe a interaction network of adaptive regulatory T cells, in which mature precursor T cells may differentiate into either adaptive regulatory T cells or effector T cells, depending on the activation state of the cell by which the antigen was presented. Using an equilibrium analysis of the mathematical model we show that, for some parameters, the network has two stable equilibrium states: one in which effector T cells are strongly regulated by regulatory T cells and another in which effector T cells are not regulated because the regulatory T cell population is vanishingly small. We then simulate different types of perturbations, such as the introduction of an antigen into a virgin system, and look at the state into which the system falls. We find that whether or not the interaction network switches from the regulated (tolerant) state to the unregulated state depends on the strength of the antigenic stimulus and the state from which the network has been perturbed. Conclusion/Significance: Our findings suggest that the interaction network studied in this paper plays an essential part in generating and maintaining tolerance against allergens and self-antigens. [ABSTRACT FROM AUTHOR]

Inappropriate T cell responses cause the four classical types of hypersensitivity immune reactions. All of these can target the kidney and cause distinct forms of glomerulonephritis. CD4+ T cells can mediate glomerular immunopathology by cytokine secretion, by activating effector cells such as macrophages or by inducing auto-antibodies or immune-complexes. Cytotoxic CD8+ T cell responses and failure of regulatory T cells may represent two additional types of anti-renal hypersensitivity. T cell activation is critically dependent on dendritic cells (DC), whose role in renal disease appears to be protective, but underlying mechanisms are largely unknown. In this paper, we summarized mechanistic information from rodent models on the roles of DC and T cells in glomerular immunopathology. [ABSTRACT FROM AUTHOR]

Background: Immune responses to malaria blood stage infection are in general defective, with the need for long-term exposure to the parasite to achieve immunity, and with the development of immunopathology states such as cerebral malaria in many cases. One of the potential reasons for the difficulty in developing protective immunity is the poor development of memory responses. In this paper, the potential association of cellular reactivity in lymphoid organs (spleen, lymph nodes and Peyer's patches) with immunity and pathology was evaluated during Plasmodium berghei ANKA infection in CBA mice. Methods: CBA mice were infected with 1 × 106 P. berghei ANKA-parasitized erythrocytes and killed on days 3, 6-8 and 10 of infection. The spleen, lymph nodes and Peyer's patches were collected, fixed in Carson's formalin, cut in 5 µm sections, mounted in glass slides, stained with Lennert's Giemsa and haematoxylin-eosin and analysed with bright-field microscopy. Results: Early (day 3) strong activation of T cells in secondary lymphoid organs was observed and, on days 6-8 of infection, there was overwhelming activation of B cells, with loss of conventional germinal center architecture, intense centroblast activation, proliferation and apoptosis but little differentiation to centrocytes. In the spleen, the marginal zone disappeared and the limits between the disorganized germinal center and the red pulp were blurred. Intense plasmacytogenesis was observed in the T cell zone. Conclusion: The observed alterations, especially the germinal center architecture disturbance (GCAD) with poor centrocyte differentiation, suggest that B cell responses during P. berghei ANKA infection in mice are defective, with potential impact on B cell memory responses. [ABSTRACT FROM AUTHOR]

The need for an effective HIV/AIDS vaccine is imperative to halt a pandemic that involves more than 40 million individuals worldwide as of 2005 and is causing enormous socio-economic losses, especially in developing countries (DC). The overall failure of more than two decades of HIV vaccine research justifies the demands for a concerted effort for the rapid development of new and efficacious vaccines against HIV/AIDS. In this context, building international collaborative networks is a must for speeding up scientific research and optimizing the use of funding in a synergistic fashion, as resources for HIV/AIDS are limited and do not involve most of the biggest Pharmas that are more interested in drug discovery. The AIDS Vaccine Integrated Project (AVIP) consortium is an example of synergistic partnership of international European Union and DC experts with a common research goal. AVIP is a European Commission-funded (FP-6), consortium-based, 5-year program directed to the fast development of new HIV/AIDS vaccine candidates to be tested in phase I clinical trials in Europe for future advancement to phase II/III testing in DC. To ensure their rapid development, AVIP novel combined vaccines include both regulatory and structural HIV antigens, which have already been tested, as single components, in phase I clinical trials. In particular, such combination vaccines may be superior to earlier vaccine candidates, the vast majority of which are based only on either structural or regulatory HIV products. In fact, the generation of immune responses to both types of viral antigens expressed either early (regulatory products) or late (structural products) during the viral life cycle can maximize immune targeting of both primary or chronic viral infection. Further, the rational design of combined vaccines allows exploitation of immunomodulatory functions of HIV regulatory proteins, which can improve immunity against structural vaccine components. The building of the AVIP consortium and its scientific strategy will be reviewed in this paper as an example of the establishment of a consortium regulated by a specific intellectual property agreement. [ABSTRACT FROM AUTHOR]

The human HS1,2 enhancer of the immunoglobulin (Ig) heavy chain 3′ enhancer complex plays a central role in the regulation of Ig maturation and production. Four common alleles HS1,2-A*1, *2, *3, *4 are directly implicated with the transcription level and at least one of them, HS1, 2-A*2, seems to be related to immune disorders, such as coeliac disease, herpetiform dermatitis and Berger syndrome. Given their clinical significance it is of interest to know the distribution of HS1,2-A variants in populations from different continents, as well as to determine whether the polymorphism is associated to specific evolutionary factors. In this paper we report the distribution of the HS1,2-A polymorphism in 1098 individuals from various African, Asian and European populations. HS1,2-A*3 and HS1,2-A*4 alleles are at their highest frequencies among Africans, and HS1,2-A*2 is significantly lower in Africans in comparison with both Europeans and, to a lesser extent, Asians. Analysis of molecular variance of the allele frequencies indicates that the HS1,2-A polymorphism can be considered as a reliable anthropogenetic marker. [ABSTRACT FROM AUTHOR]

The heart can be seriously affected in human trichinellosis, and cardiac involvement can cause death. Experimental infections in rats have suggested the possible participation of immunopathological processes. The aim of the present paper was to investigate the possible presence in trichinellosis patient sera of antibodies recognizing host tissues and particularly the myocardium. Nineteen sera from late period trichinellosis patients, who acquired infection in the Poznan region (Poland), were tested by immunoblot on extracts from normal rat or human heart ventricle wall, spleen, placenta, kidney and skeletal muscle. Patients' sera recognized several antigens that were not recognized by normal sera. On rat and human heart ventricle wall, a high proportion of sera (42%) reacted with a protein of 68 kDa (P< 0.05 compared to normal sera). The reactivity with this antigen, however, was not significantly different in patients with or without cardiac involvement. When sera were tested on skeletal muscle we found that 47% reacted with a protein of 27 kDa and 53% reacted with a protein of 41 kDa (P<0.05 for both proteins, compared with normal sera). The reactivity against the 68 kDa antigen and against the 27 and 41 kDa skeletal muscle antigens was not observed on kidney, placenta and spleen extracts. Moreover, very few bands were observed on these tissues as compared to heart and skeletal muscle tissues, thus suggesting a high tissue specificity of the reactivity of trichinellosis sera. In conclusion, this study identifies organ-specific autoantibodies in trichinellosis patient sera, their role in the pathogenesis of cardiac involvement being still unclear. [ABSTRACT FROM AUTHOR]

CD4 T cells play a central role in the immune response to malaria. They are required to help B cells produce the antibody that is essential for parasite clearance. They also produce cytokines that amplify the phagocytic and parasitocidal response of the innate immune system, as well as dampening this response later on to limit immunopathology. Therefore, understanding the mechanisms by which T helper cells are activated and the requirements for development of specific, and effective, T cell memory and immunity is essential in the quest for a malaria vaccine. In this paper on the CD4 session of the Immunology of Malaria Infections meeting, we summarize discussions of CD4 cell priming and memory in malaria and in vaccination and outline critical future lines of investigation. B. Stockinger and M.K. Jenkins proposed cutting edge experimental systems to study basic T cell biology in malaria. Critical parameters in T cell activation include the cell types involved, the route of infection and the timing and location and cell types involved in antigen presentation. A new generation of vaccines that induce CD4 T cell activation and memory are being developed with new adjuvants. Studies of T cell memory focus on differentiation and factors involved in maintenance of antigen specific T cells and control of the size of that population. To improve detection of T cell memory in the field, efforts will have to be made to distinguish antigen-specific responses from cytokine driven responses. [ABSTRACT FROM AUTHOR]

The combination of optic neuritis and myelitis, the so-called Neuromyelitis optica is an uncommon pattern of demyelinating disorder. In 1870, Sir Thomas Clifford Allbutt first reported the association and Erb published a comparable report. Gowers and Dreschfeld described other instances in the 19th century. This paper attempts to review the syndrome to consider whether it merits recognition as a disease, sui generis, or rather as a syndrome symptomatic of multiple sclerosis, acute disseminated encephalomyelitis, and other immunological disorders. Two forms are distinguished: a monophasic illness, and a relapsing form. The claimed differential features separating it from classical multiple sclerosis are appraised. Modern immunology suggests an antibody-dependent, complement-mediated pathogenesis.Spinal Cord (2005) 43, 631–634. doi:10.1038/sj.sc.3101758; published online 14 June 2005 [ABSTRACT FROM AUTHOR]

Tryptase has been suggested to take part in the pathophysiology of psoriasis mainly through the production of C3a by cleaving C3. However, studies using tryptase preparations of high purity do not support this notion. Therefore, although tryptase is unanimously believed to be involved in the immunopathogenesis of psoriasis, no convincing mechanism has been proposed for its role. This paper proposes several mechanisms by which this enyme may exert its role in the pathobiology of psoriasis. Tryptase is a mitogen for epithelial cells and stimulates IL-8 production and ICAM-1 expression by these cells. It also induces the expression of mRNA for IL-1β and IL-8 and stimulates the selective release of IL-8 from endothelial cells and TNF-α, IL-1β, and IL-6 from lymphocytes and monocytes. Besides itself being a chemoattractant for neutrophils, tryptase activates mast cells and generates kinins from kininogen, thereby playing a crucial role in leukocyte infiltration into psoriatic lesions. This enzyme also induces leukocyte infiltration partly through activating endothelial PAR-2, which contributes to leukocyte rolling, adherence and recruitment by inducing the release of endothelial platelet-activating factor. Through activating PAR-2, tryptase could also trigger the development of Langerhans cells which play a crucial role in the pathophysiology of psoriasis. This enzyme is a mitogen for fibroblasts, which are probably involved in the pathophysiology of psoriasis through production of insulin-like growth factor-I (IGF-I). Tryptase is a gelatinase and also activates stromelysin-1 (MMP-3), thereby contributing to the disruption of psoriatic basement membrane and to the joint damage seen in psoriatic arthritis. Increase of tryptase levels following trauma could also provide a mechanism for Koebner phenomenon seen in psoriasis. [ABSTRACT FROM AUTHOR]

Abstract: In 1972 Guido Biozzi selectively bred mice to study the immunopathological mechanisms underlying polygenic diseases. One line, the Biozzi antibody high (AB/H) mouse (now designated the ABH strain) was later found to be highly susceptible to many experimentally induced diseases such as autoimmune encephalomyelitis, autoimmune neuritis, autoimmune uveitis, as well as virus-induced demyelination and has thus been a key mouse strain to study human inflammatory neurological diseases. In this paper we discuss the background of the Biozzi ABH mouse and review how studies with these mice have shed light on the pathogenic mechanisms operating in chronic neurological disease. [Copyright &y& Elsevier]

Abstract: In this paper we undertake a combined analysis of several studies in which marmoset monkeys received immunotoxic lesions of the cortical cholinergic projections from the basal nucleus of Meynert (NBM) bilaterally and/or in combination with immunotoxic lesions of other parts of the cholinergic system or ablations of the target inferotemporal neocortical area. Analysis of the mean learning scores across all visual discriminations learning tasks for each lesion combination revealed highly significant impairments where the NBM was lesioned bilaterally or where an NBM lesion in one hemisphere was crossed with an inferotemporal cortical ablation in the other hemisphere. This demonstrates that the cholinergic projection from the NBM to the major target area of neocortex involved in visual discrimination learning, i.e. the inferotemporal cortex, makes an important contribution to the perceptuo-mnemonic processes necessary for this type of learning. A new study demonstrates a significant effect of a subtotal bilateral cholinergic lesion confined to the NBM on a concurrent object-reward association task using black objects which is perceptually and mnemonically demanding. These results do not preclude the possibility that cholinergic projections from the NBM to other parts of the neocortex make a contribution to other cortical functions which are not mnemonic. It is well established that lesions of the cholinergic projection from the diagonal band of Broca disrupts the mnemonic functions of the hippocampus. The results described here suggest that degeneration of the cholinergic projections in Alzheimer''s disease and other dementias will contribute to the loss of those mnemonic functions which are dependent on the neocortex. [Copyright &y& Elsevier]

Lichen planus is a disorder characterized by lesions of the skin and oral mucous membranes. Although many patients have involvement of both skin and oral mucosa at some stage during the progress of the disease, a larger group has oral involvement alone. It has been reported that oral lichen planus (OLP) affects one to two percent of the general population and has the potential for malignant transformation in some cases (1, 2). Like many chronic inflammatory skin diseases, it often persists for many years. Numerous disorders may be associated with OLP such as graft-vs.-host disease and Hepatitis C virus infection (3), however, it is unclear how such diverse influences elicit the disease and indeed whether they are identical to idiopathic OLP. Available evidence supports the view that OLP is a cell-mediated immunological response to an induced antigenic change in the mucosa (4-6). Studies of the immunopathogenesis of OLP aim to provide specific novel treatments as well as contributing to our understanding of other cell-mediated inflammatory diseases. In this paper, the interactions between mast cells and T cells are explored from the standpoint of immune regulation. From these data, a unifying hypothesis for the immunopathogenesis of OLP is then developed and presented. [ABSTRACT FROM AUTHOR]

The pathophysiology of viral myocarditis is still a matter of debate. Humoral autoimmunity in postviral heart disease remains an attractive but complex hypothesis. Antigenic mimicry with or without cytolytic antibody properties has been shown to play a role in the immunopathogenesis of myocarditis with respect to sarcolemmal/myolemmal epitopes (including the beta-receptor), myosin and some mitochondrial proteins including the antinucleotide translocator (ANT)-carrier and dihydrolipoamid dehydrogenase. Today, refined two-dimensional Western blots are able to identify receptors and enzymes that are target of a humoral immune response or the consequence of an “immunization process.” A humoral immune response to an invading agent will most likely lead to immunodestruction first. After conversion to IgG, the continuing antibody response may indicate the healing or healed process and last for many years or life-long. This paper reviews our present knowledge on the humoral immune response in myocarditis and its interplay with the viral agents and the other components of the immune system. [Copyright &y& Elsevier]

The cleavage of complement may be an important immunopathologic mechanism in the development of gingival inflammation. Utilizing the experimental gingivitis model, cleavage of C3, C4 and B was assessed in gingival fluid following abstention from oral hygiene. 4 male dental students performed stringent oral hygiene measures until the gingival index approached 0, then refrained from any oral hygiene for 21 days. Gingival fluid, sampled with filter paper strips from the mesial surface of all maxillary premolars at 0, 7, 14, and 21 days, was assayed for C3, C4 and B cleavage by multilayer crossed-immunoelectrophoresis. Clinical indices were assessed following gingival fluid sampling. The subjects, who were plaque-free (PI = 0) at the beginning of the study. showed significant plaque accumulation at day 21(87% of sites with P1 &ges; 2). Approximately 90% of the sites were free from clinical inflammation (GI = 0) at the start, but gingivitis increased with time such that 25% of the sites had GI scores of 2 at day 21. Bleeding on probing to the base of the pocket was not observed at day 0, but was observed at 62% of sites by day 21. Statistical analyses showed that all 3 indices significantly increased with time. The %C3 cleavage increased from a mean of 24% at day 0, to 35%, 45% and then 57% at days 7, 14 and 21, respectively, and both days 14 and 21 demonstrated significantly greater C3 conversion than that seen at day 0. The Spearman rank-order correlation coefficient for %C3 conversion versus time was p = 0.52, significant at the p < 0.0001 level. B cleavage to Bb was commonly seen, but C4 cleavage to C4c was never observed. Thus, during experimental gingivitis, %C3 cleavage significantly increased with plaque accumulation and resultant gingivitis, correlating with gingivitis at p=0.64. These results suggest that cleavage of complement may be an important factor in the initiation of gingival inflammation. [ABSTRACT FROM AUTHOR]

Immunofluorescent studies are currently being done on patients with pemphigus, pemphigoid, dermatitis, lupus erythematosus and its variants, the cutaneous prophyrias, scarring alopecia, erosive mouth lesions, light-sensitive disorders, and cutaneous vasculitis. In this paper I shall review some of the recent advances in immunopathology and report the results that have been obtained in our laboratory. [ABSTRACT FROM AUTHOR]

In developing an effective clinical tool against COVID-19, we need to consider why SARS-CoV-2 infections develop along remarkably different trajectories: from completely asymptomatic to a severe course of disease. In this paper we hypothesize that the progressive exhaustion and loss of lymphocytes associated with severe stages of COVID-19 result from an intracellular energy deficit in an organism which has already been depleted by preexisting chronic diseases, acute psychological stress and the aging process. A bioenergetics view of COVID-19 immunopathology opens a new biophysical opportunity to enhance impaired immune function via proposed pathways of photomagnetic catalysis of ATP synthesis, regenerative photobiomodulation and the ultrasonic acceleration of cell restructuring. Moreover, we suggest that a coherent application of multiple biophysical radiances (coMra) may synergistically enhance energy-matter-information kinetics of basal self-regeneration of cells and thus improve immune function and accelerate recovery. Unlabelled Image • Bioenergetics offers a unifying framework of COVID-19 immunopathology. • Functional reserve of immune cells depends on the kinetics of basal housekeeping. • Various biophysical stimuli enhance the kinetics of cellular self-regeneration. • A coherent application of multiple radiances has potential to treat COVID-19. [ABSTRACT FROM AUTHOR]

Erich Letterer (1895–1982) is without any doubt one of the most renowned German pathologists of the 20th century. As the eponym of the "Letterer-Siwe disease" and as a pioneer in the field of immunopathology, he made his mark in medical history. Less well known is the fact that Letterer achieved the decisive career step – the call to a full professorship – in the Third Reich, at the explicit request of authoritative National Socialists. In post-war Germany, on the other hand, Letterer was considered a politically unencumbered, honorable scientist. But how do these findings fit together? Did Letterer serve the Nazi regime or did he achieve his high positions despite a politically unbending, straightforward attitude? These questions are the main focus of the present article, which also traces Letterer's academic career and oeuvre. The paper is based on primary sources from various federal and regional archives, most of which have been evaluated for the first time; they have been compared and supplemented with the existing secondary literature. It concludes that Letterer was politically loyal during the Nazi era – as evidenced by memberships in various Nazi organizations – and that he enjoyed political support. Letterer's self-image of a politically aloof, blameless scholar does not agree with the sources. However, Letterer did not belong to those university lecturers who owed their career in the Third Reich mainly to political reasons. Rather, he was a renowned pathologist and scientist who also proved to be politically reliable in the decisive phase of his career. [ABSTRACT FROM AUTHOR]