First line of defence

There are many factors in mucosal secretions that contribute to innate immunity and the 'first line of defence' at mucosal surfaces. Few studies, however, have investigated the effects of exercise on many of these 'defence' factors. The aim of the present study was to determine the acute effects of prolonged exercise on salivary levels of selected antimicrobial peptides (AMP) that have not yet been studied in response to exercise (HNP1-3 and LL-37) in addition to immunoglobulin A (IgA). A secondary objective was to assess the effects of exercise on saliva antibacterial capacity. Twelve active men exercised on a cycle ergometer for 2.5 h at approximately 60% of maximal oxygen uptake. Unstimulated whole saliva samples were obtained before and after exercise. There was a significant decrease (P < 0.05) in salivary IgA:osmolality ratio, following exercise, but IgA concentration and secretion rate were unaltered. Salivary HNP1-3 and LL-37 concentrations (P < 0.01 and P < 0.05, respectively), concentration:osmolality ratios (P < 0.01) and secretion rates (P < 0.01) all increased following exercise. Salivary antibacterial capacity (against E. coli) did not change. The increased concentration of AMPs in saliva may confer some benefit to the 'first line of defence' and could result from synergistic compensation within the mucosal immune system and/or airway inflammation and epithelial damage. Further study is required to determine the significance of such changes on the overall 'defence' capacity of saliva and how this influences the overall risk for infection.

Today, the proportion of elderly and senile people is steadily growing throughout the world. The most important factors in the first line of immune defense of the mucous membranes of the upper respiratory tract are β-defensins, which are a group of secretory proteins with antimicrobial activity. The aim of this study was to study the expression of genes for antimicrobial peptides β-defensins and the composition of the microbiome of the mucous membranes of the upper respiratory tract in elderly people and long-livers with various aging phenotypes.The main study group included 67 centenarians and 49 elderly people, who were further divided into two subgroups depending on the course of aging (pathological and successful aging). Nucleic acids were isolated from nasopharyngeal scrapings and the expression levels of the DEFB1 and DEFB4 genes were determined using real-time polymerase chain reaction. The composition of the microbiota in nasopharyngeal swabs was determined by MALDI-TOF mass spectrometry.In analyzing the expression of the DEFB1 gene in elderly people and centenarians with successful and pathological aging phenotypes, no difference was revealed between the groups. Expression of the DEFB4 gene was increased in centenarians with pathological aging compared to centenarians with successful aging and in the elderly group. Excessive production of antimicrobial peptides is dual in nature; on the one hand, they provide the first line of defense against microorganisms, and on the other, they are cytotoxic to their own cells. An increase in the expression of the DEFB4 gene during aging may be due to an increase in the number of pathogen-associated molecular patterns, which can be one’s own microbiota and/or components of microbial metabolism. Analysis of the microbiota composition showed an increase in biodiversity in individuals with a successful aging phenotype compared to a pathological phenotype. Particular attention is paid to Staphylococcus spp., the species composition of which depends on the aging phenotype. In the pathological aging group, the frequency of St. aureus colonization is significantly higher than in the successful aging group.Thus, overexpression of the DEFB4 gene and changes in the composition of the microbiota of the mucous membranes of the upper respiratory tract may be one of the mechanisms explaining the increased susceptibility to infections in various aging phenotypes.

By comparing natural immunity to Aspergillus fumigatus (AF) in vivo with the action of human or mouse phagocytes against AF in vitro, we delineated two sequential lines of defense against AF. The first line of defense was formed by macrophages and directed against spores. Macrophages prevented germination and killed spores in vitro and rapidly eradicated conidia in vivo, even in neutropenic and athymic mice. The second was the neutrophilic granulocyte (PMN), which protected against the hyphal form of AF. Human and mouse PMN killed mycelia in vitro. Normal, but not neutropenic mice, stopped hyphal growth, and eradicated mycelia. Either line of defense acting alone protected mice from high challenge doses. Natural immunity collapsed only when both the reticuloendothelial system and PMN were impaired. These findings are in keeping with the clinical observation that high doses of cortisone and neutropenia are the main risk factors for invasive aspergillosis. Cortisone inhibited the conidiacidal activity of mouse macrophages in vivo and of human or mouse mononuclear phagocytes in vitro. Cortisone damaged this first line of defense directly and not through the influence of T lymphocytes or other systems modifying macrophage function as shown in athymic mice and in vitro. In addition, daily high doses of cortisone in mice reduced the mobilization of PMN so that the second line of defense was also impaired. Thus, cortisone can break down natural resistance on its own. Myelosuppression rendered mice susceptible only when the first line of defense was overpowered by high challenge doses, by activated spores that cannot be killed by macrophages, or by cortisone suppression of the conidiacidal activity of macrophages. The host, thus, can call upon two independent phagocytic cell lines that form graded defense systems against aspergillus. These lines of defense function in the absence of a specific immune response, which seems superfluous in the control and elimination of this fungus.

Experimental modulation of cellular glutathione levels has been used to explore the role of glutathione in cadmium toxicity. Mice treated with buthionine sulfoximine [an effective irreversible inhibitor of gamma-glutamylcysteine synthetase (EC 6.3.2.2) that decreases cellular levels of glutathione markedly] were sensitized to the toxic effects of CdCl2. Mice pretreated with a sublethal dose of Cd2+ to induce metallothionein synthesis were not sensitized to Cd2+ by buthionine sulfoximine. Mice sensitized to Cd2+ by buthionine sulfoximine were protected against a lethal dose of Cd2+ by glutathione mono isopropyl ester (L-gamma-glutamyl-L-cysteinylglycylisopropyl ester), but not by glutathione. These results are in accord with studies that showed that glutathione mono esters (in contrast to glutathione) are efficiently transported into cells and converted intracellularly to glutathione. The findings indicate that intracellular glutathione functions in protection against Cd2+ toxicity, and that this tripeptide provides a first line of defense against Cd2+ before induction of metallothionein synthesis occurs. The experimental approach used here in which cellular levels of glutathione are decreased or increased seems applicable to investigation of other types of metal toxicity and of other glutathione-dependent biological phenomena.

Most interactions between plants and fungi or Oomycetes do not result in a successful infection but are thwarted by the host (Thordal-Christensen, 2003; Lipka et al., 2008). In many cases, the obvious visible first line of defence is the papilla, a cell wall apposition (CWA) laid down by the host at the site of attempted penetration by the fungus or Oomycete on the inside of the host cell wall. CWA are observed in many plant species but are best studied in the cereal–powdery mildew interactions where the CWA comprises the inner papilla surrounded by an outer halo. Histological and chemical analyses demonstrate the complexity of the papillae, which comprise callose, protein, and various phenolic compounds and inorganic compounds, especially opal silica and, at least transiently, reactive oxygen species (see Zeyen et al., 2002, for a review). It is clear that papillae play a significant role, since penetration is often arrested by papillae, but as to which components of papillae are important for successful defence against a particular species pathogen is unclear. In other words, the demonstration of the complexity of papillae is not a demonstration of their role in disease resistance and presents the question as to why they are so complex. What is the role of the individual components of the papilla? There are two approaches which use the tools of forward and reverse genetics to determine the role of individual components of papillae which will answer this question, at least in part. The regulation of the formation of papillae has been studied genetically in both barley and Arabidopsis. Mutants have been obtained in barley exhibiting resistance, and indeed the mlo mutant confers race-non-specific resistance in both species (Consonni et al., 2006). Other Arabidopsis mutations contribute to the assembly of papillae (Collins et al., 2003, 2007). The physiological role of the Arabidopsis gene products is uncertain in some cases (Lipka et al., 2008). Thus the forward genetics approach has favoured the identification of regulatory, like mlo, and mechanistic components, like Pen1, but has not yielded mutations in the phenolic biosynthetic pathways associated with papilla formation. The nature of the first line of defence in cereals is still something of a mystery despite many years of study. We know much but there is still much to learn. Wei and colleagues have previously developed Triticum monococcum L. (Einkorn, a diploid wheat) as an excellent model system to use as an alternative to barley. In this issue, the study by Bhuiyan et al. (2009) uses a forward genetic approach to study the role of papilla components in Einkorn wheat infected with the powdery mildew fungus Blumeria graminis. The result is compelling evidence that lignification of papillae plays an important role in defence against penetration by this fungus. Lignification is, in essence, the generation of wood. The process can be considered to comprise two phases, firstly, the biosynthesis of monolignols, the building bricks, and, secondly, the assembly and polymerization of these bricks in the papilla. This paper represents an in-depth study of the first phase, which is illustrated in Fig. 1 of Bhuiyan et al. (2009). The approach taken has been to screen an expression sequence tag (EST) library prepared from the epidermis of T. monococcum infected with B. graminis f. sp. tritici (Bgt) (Liu et al., 2005; Bhuiyan et al., 2007) which is predicted to be enriched for first line defences against Blumeria graminis (Wei et al., 1998; Collinge et al., 2002). This yielded 13 cDNAs representing eight genes encoding enzymes involved in monolignol biosynthesis, according to their bioinformatical analysis. That six of these transcripts exhibit nearly synchronized accumulation patterns, as revealed by Northern blotting of entire leaves and epidermal expression, as revealed by RT PCR, is an excellent indication of their role in papilla formation. Proof of the importance of monolignol biosynthesis comes from the reverse genetics of transient gene silencing of four of the biosynthetic genes and an additive effect was obtained by combining three of the genes pair-wise. Thus, silencing gave a statistically significant increase in the efficiency of penetration. In the control, roughly 40% of penetration attempts were successful by the host powdery mildew fungus Bgt and increased 4-fold in the non-host powdery mildew fungus, Bg. f.sp. hordei, which infects barley. The double silenced constructs gave over 70% successful penetration rates. The genes included TmPAL, which encodes the first enzyme in the phenylpropanoid pathway, and can be predicted to have other roles in defence in grasses. For example, flavonoid biosynthesis has been seen to be induced in barley in response to B. graminis (Christensen et al., 1998a, b). The combination of TmPAL with genes encoding the two final biosynthetic enzymes of

Mucosal surfaces are important physical barriers whose main function is to protect the systemic environment of the body against microbial invasion. It is the first line of defense to protect the animal and also functioning as an active immune tissue. Four mucosal-associated lymphoid tissues (MALTs), which start the immune responses are skin, gills, gut, and nose, have been reported in fish. Humoral and cellular immunity, their regulation and the factors that influence the response in these MALTs are still not well known in most fish species. These are principle doorway for microbial invasion and as such developing protective vaccines against these pathogens can serve as first line of defense against infections. In this review we have summarized the role of fish mucosal immunity to provide the first line of defense mechanism against microbial invasion. Increased knowledge of fish mucosal immune system will facilitate the development of novel vaccination strategies in fish. Keywords: Mucus, mucosal immunity, MALT, B cells, T cells Cite this Article Supriya Dash, Jayashree Nanda, Soumyashree Barik et al. Mucosal Defense Mechanism in Fish: An Overview. Research & Reviews: A Journal of Immunology . 2017; 7(3): 1–5p.

Leukocytes, also called white blood cells, can be categorized into three main groups, granulocytes, monocytes, and lymphocytes, which can be further classified into various subgroups. Lymphocytes are known to intervene in immune responses such as secreting cytokines, killing cells, or the production of antibodies. Monocytes/macrophages participate in chronic inflammation by synthesizing numerous mediators and eliminating various pathogens. The main type of granulocytes is the neutrophil, also called the polymorphmononuclear (PMN) leukocyte; these are usually not found in normal "healthy" tissue and are referred to as 'the first line of defense' against invading pathogens. However, besides the beneficial microbicidal activity of neutrophils, this cell type is also involved in the pathophysiology of organ damage in ischemia/reperfusion, trauma, sepsis, or organ transplantation. The exact role or function of leukocytes during inflammatory processes is far from being elucidated and can only be estimated from the enormous amount of literature on these cell types. The present review will focus mainly on PMN leukocytes and their ambiguous role in normal and inflamed tissue.

Avoidance of Parasites

Neutrophils are a type of granulocyte important in the "first line of defense" of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low-molecular-weight activity-based probes that specifically target the active sites of neutrophil proteases.

Paramedics play a critical role as the first line of defense in emergency medical systems, delivering rapid, life-saving interventions in pre-hospital settings. This systematic review aims to evaluate the impact of paramedic-led care on pre-hospital emergency outcomes, including survival rates, response time, and clinical effectiveness. A structured search was conducted across major databases, including PubMed, Scopus, and Web of Science, following PRISMA guidelines. Eligible studies published between 2015 and 2025 were included based on predefined criteria focusing on paramedic interventions and measurable patient outcomes. The findings indicate that paramedics significantly improve patient survival, particularly in time-sensitive conditions such as cardiac arrest and trauma, through early assessment, rapid intervention, and advanced clinical decision-making. Moreover, reduced response times and the integration of advanced technologies further enhance pre-hospital care efficiency. Overall, paramedics are essential contributors to improving emergency care outcomes and healthcare system performance.

The epithelia constitute a major barrier to the environment and provide the first line of defense against invading microbes. Antimicrobial peptides are emerging as participants in the defense system of epithelial barriers in general. Originally we isolated the human antimicrobial peptide LL-37 from granulocytes. The gene (CAMP or cathelicidin antimicrobial peptide) coding for this peptide belongs to the cathelicidin family, whose members contain a conserved pro-part of the cathelin type. The human genome seems to have only one gene of this family, whereas some mammalian species have several cathelicidin genes. In the present work we demonstrate up-regulation of this human cathelicidin gene in inflammatory skin disorders, whereas in normal skin no induction was found. By in situ hybridization and immunohistochemistry the transcript and the peptide were located in keratinocytes throughout the epidermis of the inflammatory regions. In addition, the peptide was detected in partially pure fractions derived from psoriatic scales by immunoblotting. These fractions also exhibited antibacterial activity. We propose a protective role for LL-37, when the integrity of the skin barrier is damaged, participating in the first line of defense, and preventing local infection and systemic invasion of microbes.

Both exogenous and endogenous compounds can induce the expression of cytochrome P450 genes. The insect cytochrome P450 genes related to insecticide resistance are likely to be expressed as the “first line of defense” when challenged with insecticides. In this study, four cytochrome P450 genes, SinvCYP6B1, SinvCYP6A1, SinvCYP4C1, and SinvCYP4G15, were firstly isolated from workers of the red imported fire ant (Solenopsis invicta) through rapid amplification of cDNA ends (RACE) and sequenced. The fipronil induction profiles of the four cytochrome P450 genes and the two previously isolated CYP4AB1 and CYP4AB2 were characterized in workers. The results revealed that the expression of SinvCYP6B1, SinvCYP6A1, CYP4AB2, and SinvCYP4G15, increased 1.4-fold and 1.3-fold more than those of acetone control, respectively, after 24 h exposure to fipronil at concentrations of 0.25 μg mL−1 (median lethal dose) and 0.56 μg mL−1 (90% lethal dose), while no significant induction of the expression of CYP4AB1 and SinvCYP4C1 was detected. Among these genes, SinvCYP6B1 was the most significantly induced, and its maximum expression was 3.6-fold higher than that in acetone control. These results might suggest that multiple cytochrome P450 genes are co-up-regulated in workers of the fire ant through induction mechanism when challenged with fipronil. These findings indicated that cytochrome P450 genes play an important role in the detoxification of insecticides and provide a theoretical basis for the mechanisms of insecticide metabolism in the fire ant.

Interleukin (IL)-17-producing T cells play a critical role in the immune response against microbial pathogens. Traditionally, experimental studies have focused upon understanding the activity of IL-17-producing T cells which differentiate from naive T cells in the peripheral immune system. However, we have demonstrated previously that IL-17-producing T cells are also present in the thymus of naive wild-type mice and can be co-activated there by microbial stimuli. Other studies have supported the concept that IL-17-producing thymocytes have a specific role in the immediate defence against microbial pathogens, which is independent from the development of an adaptive immune response. Given an important role of the thymus in systemic bacterial infection and sepsis, in this study we investigate the effect of a broad spectrum of bacteria and cell wall components on thymocyte cytokine production. Surprisingly, we find that all types of bacteria investigated (including non-pathogenic species) uniformly activate IL-17-producing thymocytes upon α-CD3 stimulation. In contrast, there is a heterogeneous effect on IL-6 and interferon (IFN)-γ-production with Gram-negative bacteria inducing far higher frequencies of IL-6- and IFN-γ-producing thymocytes than Gram-positive bacteria. We conclude that IL-17-producing thymocytes constitute a 'first line of recognition', but not a 'first line of defence' against bacteria in general. Their activity might lead to immune activation, but not necessarily to a pathological inflammatory disease condition. The difference between these two states might be determined by other immunological effector molecules, such as IL-6 and IFN-γ.

Regulatory roles of dermal type 2 innate lymphoid cells

At the highest abstraction level, an attempt by a social engineer to exploit a victim organisation either attempts to achieve some specific target (denial of service, steal an asset, tap some particular information) or it wishes to maximise an outcome, such as to disable the organisation by a terrorist attack or establish a permanent parasitic relationship (long-term espionage). Seen as dynamic processes, the first kind of exploit is a controlling ('balancing') feedback loop, while the second kind is a reinforcing feedback loop. Each type of exploit meets a first line of defence in control processes or in escalating ('reinforcing') processes of resistance. The possible combinations of the two modes of attack and the two modes of defence yield four archetypes of exploit and natural defence. Predictably, the social engineer would seek to outsmart the first line of defence; it is shown that each archetype implies a particular strategy to do so. Anticipation of these modes of attack must be the starting point for an effective multilayered defence against social engineering attacks.