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Platelets are primarily associated with their main function, hemostasis, although it is known that these cells also exhibit biological activity in cancer progression, inflammation and infectious processes. During infection platelets, due to the expression of specific receptors - Toll-like receptors (TLRs) - which recognize molecular patterns associated with pathogens - pathogen-associated molecular patterns (PAMPs) - are activated by the presence of microorganism components and/or substances released from damaged cells/tissue. Further antimicrobial activity of platelets is based on their capacity for phagocytosis, generation of reactive oxygen species (ROS), and the synthesis, storage and release of proteins/peptides with antimicrobial activity. Another mechanism of platelet action is their immunomodulatory activity. It is based mainly on the ability to secrete chemotactic factors allowing the accumulation of professional immunocompetent cells at the site of infection, thus enhancing the effective eradication of an infectious agent. In chronic infections, platelets, due to release of numerous growth factors and various cytokines, support mechanisms of acquired immunity. They accelerate the maturation of dendritic cells, stimulate B cells to be immunoglobulin-producing plasma cells and potentiate the activity of T cells. Unfortunately, in certain situations (the existence of specific risk factors) the interaction of microorganisms with activated platelets may also be the cause of pathology within the cardiovascular system.

Toll-like receptors (TLRs) are pattern recognition receptors crucial for the innate and adaptive immune response to pathogen-associated molecular patterns (PAMPs). TLR stimulation via microbial products activates antigen-presenting cells, influences the function of T regulatory cells (Treg), determines the Th1/Th2 balance and Th17 cell differentiation, and controls cytokine production in mast cells and activation of eosinophils. The role of TLR receptors in pathogenesis of allergic diseases results from the biological function that they play in activation and regulation of the immune response. However, the exact role still remains a controversial area. Whereas numerous epidemiological studies mainly indicate a protective effect of microbial exposure, experiments show that innate immune stimulation via TLRs may be involved in both development of and protection against allergic diseases. Timing, dose, site and intensity of exposure to environmental factors and host genetic predisposition are clearly crucial to understanding the interaction between innate immune stimulation and allergy development.Furthermore, extensive clinical trials suggest that ligands for TLRs provide new therapeutic targets for protection against and treatment of asthma and allergic rhinitis. The aim of this review is to summarize the current knowledge about the role of TLRs in pathogenesis of allergic diseases. We will further discuss how we can reconcile inconsistencies in the results of existing studies and review information on the potential use of ligands for TLRs in allergy prevention and therapy.

The mechanism of innate immunity is based on the pattern recognition receptors (PRR) that recognize molecular patterns associated with pathogens (PAMPs). Among PRR receptors Toll-like receptors (TLR) are distinguished. As a result of contact with pathogens, TLRs activate specific intracellular signaling pathways. It happens through proteins such as adaptor molecules, e.g. MyD88, TIRAP, TRIF, TRAM, and IPS-1, which participate in the cascade activation of kinases (IKK, MAP, RIP-1, TBK-1) as well as transcription factors (NF-κB, AP-1) and regulatory factor (IRF3). The result of this activation is the production of active proinflammatory cytokines, chemokines, interferons and enzymes. The PRR pathways are controlled by extra- and intracellular molecules to prevent overexpression of PRR. They include soluble receptors (sTLR), transmembrane proteins (ST2, SIGIRR, RP105, TRAIL-R) and intracellular inhibitors (SOCS-1, SOCS-3, sMyD88, TOLLIP, IRAK-M, SARM, A20, β-arrestin, CYLD, SHP). These molecules maintain the balance between activation and inhibition and ensure balancing of the beneficial and adverse effects of antigen recognition.

Toll-like receptors (TLRs) are a pivotal part of our innate immune response. They recognize a wide variety of pathogens and instigate an immune response, thus facilitating the removal of the disease-causing agent. Due to the intense nature of this response its strict control is of key importance, as a prolonged inflammatory signal leads to carcinogenesis and autoimmune disorders. The signaling cascade initiated by the activated TLR is complex and consists of multiple stages. It involves a variety of adaptor proteins, protein kinases and effector transcription factors. The number of stages in this process enables many possible checkpoints and ways of regulation. Signal modulation involves differentiated expression of TLRs, splicing variants of their adaptor proteins, enzymes modifying proteins engaged in the cascade and many more. This review focuses on endogenous factors responsible for controlling the TLR-dependent inflammatory response as well as on pharmacological therapies designed for regulating the innate immune response.

Undoubtedly, mast cells play a central role in allergic processes. Specific allergen cross-linking of IgE bound to the high affinity receptors (FcεRI) on the mast cell surface leads to the release of preformed mediators and newly synthesized mediators, i.e. metabolites of arachidonic acid and cytokines. More and more data indicate that bacteria and viruses can influence FcεRI-dependent mast cell activation. Some bacterial and viral components can reduce the surface expression of FcεRI. There are also findings that ligation of Toll-like receptors (TLRs) by bacterial or viral antigens can affect IgE-dependent mast cell degranulation and preformed mediator release as well as eicosanoid production. The synergistic interaction of TLR ligands and allergen can also modify cytokine synthesis by mast cells stimulated via FcεRI. Moreover, data suggest that specific IgE for bacterial or viral antigens can influence mast cell activity. What is more, some bacterial and viral components or some endogenous proteins produced during viral infection can act as superantigens by interacting with the VH3 domain of IgE. All these observations indicate that bacterial and viral infections modify the course of allergic diseases by affecting FcεRI-dependent mast cell activation.

There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9), but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus). It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

The article is a review of information concerning etiopathogenesis of systemic lupus erythematosus (SLE). Due to the risk of serious complications, including death, the clarification of etiology could result in substantial improvement or even complete cure of the disease. Progress in scientific research of observed disorder mechanisms together with implementation of appropriate therapies contributed to a higher detection rate, improved course and decreased mortality in SLE. However, there are still many doubts, which legitimate the need of further research. A significant role in development of the disease and further exacerbations is played by environmental factors. Therefore, decreased exposure to UV light, female sex hormone and microbial antigens is associated with improved course and decreased frequency of exacerbations. Less is known about the genetic basis of SLE, which results from a multigene disease background and complex hereditary mechanisms. It is estimated that the disease may be conditioned by around 100 genes, that only in part are functionally determined. Only part of them is already functionally characterized. The role played by most of them is still unknown. Research currently being conducted is aimed at detecting genetic polymorphism in large and genetically diverse populations. It will allow evaluation of the role of a particular gene in protein biosynthesis, which is responsible for development of regulatory process disturbances, commonly observed in the course of SLE. The article presents current directions of research and the latest advances in epidemiology as well as environmental and genetic risk factors of SLE.

Toll like receptors (TLRs) are an important component of the immune response. They are link between innate and adaptative response. Lymphocytes B express most of the toll-like receptors and they may respond to a broad spectrum of PAMP. Lymphocytes B are one of the major lymphocyte populations in secondary lymphoid tissues, where they represent up to 50% of cells population. These cells are an important element of the defense, largely by using the mechanisms associated with innate response. On the other hand, lymphocytes B are the site of EBV latency, so Burkitt lymphoma cells can may be a convenient model to study the mechanisms associated with EBV infection. The aim of study was to determine the expression of TLRs at the m-RNA level of in Burkitt lymphoma cells treated with ligands for selected TLRs. P3HR, Raji and Namalwa cells were stimulated with Pam3 (10 microg/ml), PolyI:C (25 microg/ml), LPS (10 microg/ml) and measles virus (MeV, moi 0.02). Unstimulated cells and cells treated with PMA (0.5 microg/ml) served as negative and positive controls. After incubation, from stimulated and unstimulated cells mRNA was extracted, RT-PCR reaction was performed and electrophoretic separation was made. The intensity (INT) of bands were determined using the tools for quantitative analysis. In order to analyze the expression of TLR genes, INT values for TLR2, TLR3 and TLR4 in tested cell lines are expressed as %, assuming an average level of GAPDH expression as 100%. The 25% of INT for negative control was accepted as a change in expression level. It was found that the expression of Toll-like receptors in Burkitt lymphoma cells is diverse both in terms of cell type and the type of stimulation.

Taking into account the role of mast cells in different physiological and pathological processes, as well as in host defense it seems very important to recognize mast cell receptors and their role in activation of these cells. In the last few years it has been indicated that mast cells can express Toll-like receptors (TLRs), molecules that play an essential role in the activation of innate immune response to microbial pathogens and take part in the development of adaptive immunity, as well. It has been defined that mast cells express TLR2, TLR4, TLR1 and TLR6. There is also some data proving that mast cells possess TLR5, TLR3 and TLR9 molecules. The presence of TLR7, TLR9, and TLR10 on mast cells is still unclear. Some data indicate that TLR expression by mast cells can be modulated by various cytokines, such as granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon (IFN)-g, cathelicidin LL-37 as well as by some bacterial components. It is now established that TLRs are involved in mast cell response to bacterial stimulation; some data also indicate that TLRs take part in virus-induced mast cell activation. What is more, it is now suggested that TLRs might regulate IgE-FceRI-dependent mast cell stimulation. Further research is needed to fully understand and describe the role of TLRs in mast cell biology.

The acute phase reaction is currently regarded as systemic inflammatory response and a component of innate unspecific immunological reaction. This complex response is regulated mainly by cytokines - pleiotropic mediators of metabolic and immunological reactions. Among cytokines representing various protein families and participating in inflammation one can distinguish pro-inflammatory and anti-inflammatory cytokines as well as a large interleukin-6 family occupying intermediate position. In the initiation of acute phase reaction participate various components such as Toll-like receptors recognizing foreign pathogens, inflammasomes activating interleukin-1, and protein kinases from the MAP family that finally activate transcription factor NF-kappaB involved in cytokine synthesis. Secreted cytokines are recognized by receptors of target cells and switch on expression of many genes, including those coding for acute phase proteins. Regulation of acute phase response is precise and includes not only transcription and translation but also stability of mRNA and its degradation, as well as inhibitory activity of microRNA. Disturbances in the course of acute phase reaction are responsible for auto-immunological and autoimmune diseases and various pathological states such as acute septic shock or chronic arthritis. Some acute phase proteins, and especially C-reactive protein, have important implications for clinical diagnostics and preventive medicine.

Toll-like receptors (TLRs) are part of the innate immune system. They recognize some protein, lipid, and nucleic structures that are common in microorganisms such as bacteria and viruses but not present in the human body. The stimulation of TLRs initiates the activation of an intracellular signaling network which results in the secretion of proinflammatory cytokines, mainly type I interferons, TNF-alpha, and IL-6. TLR2, TLR3, TLR4, TLR8, and TLR9 take part in the recognition of viral infections, four of them by discerning nucleic acids, with TLR3 recognizing dsRNA, TLR7 and TLR8-ssRNA, and TLR9-DNA. The role of TLRs in the development of infections and other inflammatory states, neoplasms, and autoimmune disorders is under investigation. The importance of TLRs in the natural course of hepatitis B and C and in the treatment of these diseases are the subject of particular interest. Attempts to apply TLR7 and TLR9 agonists in the treatment of chronic hepatitis type C are underway. A better understanding of the role of TLRs in the complex immunological phenomena accompanying viral hepatitis might put the therapeutic possibilities in these infections into a new perspective.

TLRs (Toll-like receptors) are found in many different vertebrate and invertebrate species. TLRs have important functions in cell activation of the nonspecific immune response as well as in the indirect specific immune response. These receptors recognize a broad range of exogenous and endogenous ligands. The biological importance of TLRs depends on their potential to recognize a great number of different agonists and antagonists, among them antigens of bacterial and viral origin as well as vertebrate and invertebrate autoantigens. The responsiveness of TLRs to endogenous ligands may contribute to the development of autoimmune diseases. Increasing interest is therefore directed towards understanding the effector mechanisms and signaling pathways associated with TLR activation. This leads to the discovery of new proteins associated with TLR signaling pathways. Furthermore, efforts are underway to modify the activity of TLRs by synthetic ligands. Among the factors used to modify TLR activity are short DNA fragments known as oligo-DNA. Oligo-DNA fragments are being evaluated in clinical trials as potential drugs to treat systemic lupus erythematosus.

Innate immunity is the fi rst line of the defensive mechanisms protecting the host from invading pathogens. Structures of pathogens called PAMPs (pathogen-associated molecular patterns) are recognized by extra- and intracellular pattern recognition receptors (PRRs), which includes three families of sensors: TLRs, NLRs, and RLRs. Knowledge of the mechanisms involving PRRs makes it possible to understand innate immune activity and the development of precise methods of preventing and treating infection at the molecular level. This article presents the molecular pathways initiated in response to pathogens.

The contributions of NK (natural killer) cells, DCs (dendritic cells), PRRs (pathogen recognition receptors), and PAMPs (pathogen-associated molecular patterns) recognized by PRRs as well as the participation of intracellular signaling pathways in innate immunity are shown. The possible involvement of a newly described group of immune cells, IKDCs (interferon-producing DCs), in innate immunity which show both NK and DC activity is presented. This review describes the mechanisms of innate immunity with the likely participation of autophagy initiated after endosomal TLR7 (Toll-like receptor 7) activation. Autophagy is able to remove intracellular bacteria or viruses by stimulating type I IFNs (interferons). A balance between PRR, especially TLR, activation and inactivation is crucial to avoid an excessive inflammatory response, as occurs in autoimmune and infectious diseases. Apart from SOCS (suppressor of cytokine signaling proteins) or Tollip (Toll-interacting protein), the possible contribution of microRNA in the regulation of innate immunity is described. The discovery of miRNA is one of the major scientific milestones in recent years and has revolutionized the way we look at many different modes of gene regulation.

Toll-like receptors (TLRs) are amongst the most highly conserved in the evolution of receptor family, being found in both immune and other cells. TLRs were observed in vascular endothelial cells, epithelial cells, microglia cells, adipocytes, and intestinal and renal cells. TLRs plays a key role in the innate immune response to a variety of pathogens. At present, very little is known about the role of TLRs in host defense against parasitic pathogen infections. The first study shows that TLRs contribute to both innate and adaptive immune responses following infection with protozoan parasite Leishmania major. The TLRs recognizing PAMPs associated with the parasite L. major are essential for the activation of the innate and adaptive immune responses to infection. A study concerning recognition of the role of TLRs in the host-parasite relationship would be an interesting challenge for future study.

The innate immune response is a universal mechanism of host defense against infection. It functions on the basis of special receptors called PRRs (pattern-recognition receptors) which recognize conserved microbial structures called PAMPs (pathogen-associated molecular patterns). Due to PRRs, the human organism is able to discriminate between self and non-self antigens. Toll-like receptors (TLRs) are a group of PRRs that play a crucial role in "danger" recognition and the induction of immune response. Cells of the immune system (macrophages, dendritic cells, mast cells, eosinophils, neutrophils, B lymphocytes), epithelial cells, endothelium, cardio-myocytes and adipocytes all recognize pathogens via TLRs. TLR stimulation via microbial products activates the innate immune response. This results in an upregulated synthesis of anti-bacterial substances and pro-inflammatory cytokines as well as the activation of dendritic cell maturation (increased expression of co-stimulatory molecules and MHC antigens), thereby becoming more effective in antigen presentation. In some cases, the innate immune response is not able to eliminate infection and requires the induction of the adaptive immune response. When activated via TLRs, antigen-presenting cells (APCs) release elevated levels of pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6, IL-8, and IL-12), chemokines, and nitric oxide (NO) and show increased expression of co-stimulatory molecules (CD40, CD80, CD86). All these changes in APC function allow the induction of the adaptive immune response, where both T and B lymphocytes play a crucial role. TLRs also play a role in the regulation of immune response via direct or indirect influence on the function of CD4+ CD25+ T regulatory cells (Tregs), which results in their induction and subsequent suppression of the immune response or a reversal of suppression (contrasuppression).

Platelets, essentially non-nucleated blood cells, are highly reactive components of the circulatory system. They have long been consigned solely to a role in thrombosis and hemostasis. Platelets release platelet-derived microvesicles (PMV), also known as platelet-derived microparticles (PMP). They are important but still under-appreciated mediators of intracellular cross-talk between platelets and other cells and modulate their function. They are formed after stimulation of platelets by an agonist, such as thrombin, collagen, and many others. Platelets can carry biological mediators; they can modulate immune responses and inflammatory events. Microparticles can be released from activated platelets and leukocytes in inflammatory events, but in atherosclerosis they can be released from apoptotic endothelial cells, lymphocytes, and monocytes. The markers of innate immunity expressed by platelets are Toll-like receptors (TLRs). The role of platelets in tumor progression and metastasis has been recognized, but the mechanism of their action remains still unclear.