β-methyl-βbutyrate (HMB) has been found to be markedly more effective for activating the immune function of T lymphocytes of mammals than α-ketoisocaproate (KIC). For activation of the T lymphocytes, β-methyl- butyric acid or an edible water-soluble salt thereof is administered to the mammal by a route through which the HMB enters the blood of the mammal. The amount administered is sufficient for effective enhancement of the blastogenesis of their T lymphocytes. The method is adapted for use with domestic mammals, including particularly cattle, sheep, and swine. HMB can also be used with humans as an immune system stimulant.
Lactating domestic mammals are fed ketoisocaproate (KIC) with a diet containing limited leucine to improve the quantity and quality of the milk produced. This feeding method is particularly applicable to dairy cattle but also can advantageously be used with nursing domestic animals including cattle, sheep, goats, horses, and swine.
Abstract: The factors underlying the ‘zoo visit effect’ (changes in animal behaviour/physiology in response to visitor presence) are still poorly understood, despite it being widely investigated. The present study examined the effect of zoo visitors on the behaviour of 17 different species of mammals at the Belo Horizonte Zoo, Minas Gerais, Brazil. The behaviour of the animals was recorded using scan (focal in one case) sampling with instantaneous recording of behaviour, during 12 continuous months. Data were analysed using a comparative method examining five different factors: diet, body weight, stratum occupied, activity cycle, and habitat, as well as three different visitor categories: small and quiet audience, medium size audience and medium noise, and large size and loud audience. Significant changes in the behaviour for each factor, especially increases in locomotor and resting behaviour, were observed in response to different visitor categories. The factors that most explained responses to visitor categories were habitat and activity cycle. Species from closed habitats compared to open habitats were significantly more impacted (more behaviour affected), probably, because they are, evolutionarily, less accustomed to visual contact with people. Diurnal species showed more behavioural changes than nocturnal ones, possibly, because they were being observed during their normal activity cycle. These results may help zoos identify which mammal species are most susceptible to the zoo visitor effect, and consequently, be more pro-active in the use of mitigating strategies.
GiMAPs were identified with BlastP and HMMER (hmmer.org) searches, using the AIG1 domain (pfam- 04548), focusing on species for which sequenced well- annotated whole genome data are available. In equivocal cases, assignments were made on the basis of a BLAST e-value difference of at least 1E-4 between similarity to the AIG1 domain and alternatives. Sequences were aligned with MAFFT 6.717b  using the accurate L-INS-I method. Positions containing over 95% gaps were removed from the alignment. The dataset and the alignment used for phylogenetic analyses are provided as Additional files 7 and 8. Maximum likelihood trees were inferred with PhyML 3.0  using the LG amino acid substitution model , with four substitution rate cat- egories approximating a gamma distribution whose rate was estimated, and an invariant category. The starting trees were computed using BioNJ and the topologies were optimised by nearest neighbour interchange and sub-tree pruning and regrafting. The branch support was estimated using approximate likelihood tests  and with the bootstrap procedure, using 100 replicates. For Bayesian Inference, Mr Bayes 3.2-cvs was used as de- scribed in Forêt et al. .
Intrusion detection technology clears the way for possible real time response to hostile intrusions to computer network systems, and provides a powerful guarantee, which effectively prevents farther harm for MANET. In this paper, an intrusion detection method based on intelligent immune threshold matching algorithm is presented, this method takes on better real- time detection and relatively low false positive rate and false negative rat, and thus it has an extensive worthiness of applications and theories in network security field.
The efficacy of inducing both humoral and T-cell-mediated immuneresponse by intramuscular or intradermal delivery of plasmids directing the expression of foreign antigens has been proven in a number of mammalian species (6, 9, 10, 15, 23, 24, 29, 53, 55). Genetic vaccination against a wide range of viral, bacterial, or parasitic antigens has been shown to induce pro- tective immunity in several rodent preclinical models (18, 47, 55, 60). However, the paucity of successful immunization in larger animals has spurred a new wave of research activity aimed at improving delivery vehicles and vector backbones (3, 31, 37, 42). The increased efficacy of DNA immunization by plasmid formulation with adjuvants or costimulatory factors has been recently reported (for a review, see reference 54). This notwithstanding, a major limitation to developing DNA- based vaccines for human prophylaxis and therapy is still pre- sented by the relatively low in vivo expression levels of the encoded antigens, primarily due to the progressive loss of DNA molecules along their journey from outside the cell to inside the nucleus. An effective way around this problem is to induce muscle regeneration by a necrotizing agent and then transfect regenerating fibers (59). However, though effective in animal models (13), this method has limited clinical applica- bility due to massive muscle necrosis.
The different thresholds used in the study allow readers to compare the utility of response behaviors in deciding on the size of the threshold and in comparing RT-only and enhanced methods under various conditions. Only the common and normative methods had a corresponding threshold value analyzed in this study. The visual and two state mixture model methods were not considered in the study to associate with a threshold, because a bimodal distribution was observed in only one of the seven items (Star item 2). It is possible that an overlap between response time distributions for engaged and disengaged examinees could lead to misclassifications. Readers who are interested in applying mixture modeling are encouraged to look at recent developments in using mixture modeling for detecting rapid-guessing (see Pokropek 2016; Ulitzsch et al. 2019). The response accuracy and response time-based methods suggested by Guo et al. (2016) were not studied. As Wise (2017) noted, findings from recent research con- flict with the assumptions regarding the probability of getting a correct response under rapid-guessing. Moreover, four items used in this study were constructed response items where the probability of receiving a correct score under random chance is 0, which is not ideal for using this method.
As shown in the Table, various groups have demon- strated the SG to be capable of eliciting robust wide- spread mucosal and systemic protective responses in following antigen presentation, routinely resulting in antibody titers higher than those seen with other immunization targets. It is notable that studies have gen- erally instilled the particular immunogen or vector (e.g. formalized S. mutans, BSA, virus, or plasmid DNA) in the absence of an adjuvant, yet still observed significant immune responses. Indeed, while complete Freund’s ad- juvant has been used in studies employing subcutaneous immunizations delivered in the vicinity of the salivary glands (reviewed in ), very few studies using intra- ductal instillation have included potential immune adju- vants in the infusate (cationic lipid transfection reagents Vaxfectin® and GAP-DLRIE/DOPE in rats, or azo dye Evans blue in dogs) [24, 27]. Studies have generally in- stilled the test vaccine in a saline vehicle, achieving not- able immune responses in the absence of an adjuvant. Given that vaccine efficacy is typically linked to antibody titer concentration, achieving high titers would be a common goal. A host of groups are exploring novel ad- juvants to enhance immunogencitiy, the needs of which may be diminished if the vaccination site were able to fa- cilitate a strong enough immuneresponse.
Regardless, the response of individuals to the de - ployed scent and control vials that we observed was low overall (i.e., mammals passed through without inves- tigating scent or control vials significantly more often than they stopped to investigate). Our findings, coupled with the large variation in the reported effectiveness of scent lures, may challenge the usefulness of olfactory attractants during surveys. Rather than deploying scent lures, it may be more effective to concentrate efforts on selection of high-quality camera locations by identify- ing appropriate habitat or detecting evidence of a target species through knowledge of its natural history. We found that camera traps with video capability were par- ticularly useful in quantifying responses at stations where attractants were deployed. Our ability to record video clips enabled us to count the number of respons- es and the duration of time spent investigating a giv- en scent station. This allows for a more sophisticated assessment of a species’ interest than counting photo- graphs or tracks associated with scent stations.
pulmonary and/or cardiovascular conditions (178). Interestingly, obesity is also associated with chronic pulmonary and cardiovascular diseases (179, 180). Upon infection with influenza virus, dendritic cells, macrophages, and lung epithelial cells upregulate the expression of cytokines and chemokines. These molecules play essential roles in the early inhibition of viral replication (181), the stimulation of an inflammatory response (118) and recruitment of immune cells to the site of infection (119). Additionally, cytokines activate natural killer (NK) cells which are among the first cell types to become mobilized during an influenza infection. NK cells assist in eliminating infected cells and help limit viral spread until a specific cell-mediated response can be assembled (182). The expression of cytokines and chemokines during an influenza virus infection occurs in a coordinated and specific cascade. Antiviral and pro-inflammatory cytokines are induced first, followed by IL-6 expression, and finally chemokines, such as monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α are expressed (183). Changes in the expression of any of these molecules can alter subsequent immune responses (184).
Cerebral tuberculosis is the most severe type of extrapulmonary disease that is in developing countries highly predominant in children. Meningeal tuberculosis is the most common form and usually begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. In comparison with the lung, Mycobacterium tuberculosis induces a very different immuneresponse when infect the central nervous system. Herein, we review several aspects of the pathogenesis and immuneresponse in pulmonary and cerebral tuberculosis in humans and experimental models and discuss the implications of this response in the cerebral infection outcome.
One intracellular bacterium, Coxiella burnetii, is a poorly understood pathogen capable of causing severe acute and chronic infection in humans. It is the only known bacterium to live and replicate in the harsh environment of the lysosome. It also is able to survive inside cells over a long period of time and delays recruitment of neutrophils by several days. We hypothesize that C. burnetii has evolved strategies to evade or delay activation of innate immune pathways in macrophages by either failing to activate these pathways or blocking activation through the use of its specialized Type IV secretion system (T4SS). While cells from many organisms are consusive to productive C. burnetii infection, macrophages from C57BL/6 (B6) mice are able to control C. burnetii replication via an unknown mechanism. We, therefore, further hypothesize that despite a lack of robust innate immune activation, C. burnetii activates a cell-intrinsic innate immune pathway in B6 macrophages. To address these overarching hypotheses, we pursued the following specific aims:
The principal function associated to the erythrocytes is oxygen and carbon dioxide transport. In addition to this gas exchange function, they also play a role in homeostasis protecting against oxidative damage and regulating blood flow distribution in skeletal muscle [15-17]. Other potential functions (Table 1) [18-44] have also been attributed to the erythrocytes for exam- ple: human erythrocytes may play a role in modulating T cell proliferation and survival by enhancing cytokine secretion and induction of the IL2R thus modulating CD4+/8+ ratios [21,45,46]. Interestingly this finding was published almost twenty years ago in sheep . A frag- mented series of publications can be identified across the vertebrates in which erythrocyte functions appear to be intimately connected to a range of physiological pro- cesses. These studies have shown that the cellular machinery and related biological processes are present in erythrocytes for intracellular signalling [16,48], tran- scription , protein synthesis  and secretion . Functional responses attributed include amongst others;
Keratinocytes express mannose-binding receptors (KCMR), TLRs and Class II MHC antigens and have also been identified as a source of cytokines, chemo- kines and antimicrobial peptides. In addition, keratino- cytes may play an important role in leprosy by participating in the epidermal immuneresponse to M. leprae (Mutis et al. 1993). Thus, this cell type possesses a highly sophisticated innate pattern recognition system in which the simultaneous recognition of a pathogen by different classes of pattern recognition re- ceptors can provide a specific immuneresponse or, in the case of commensals, a lack of a response to micro- organisms (Lyrio et al. 2015). Furthermore, keratino- cytes can distinguish between pathogenic and commensal microorganisms (Pivarcsi et al. 2005). In skin biopsy sections obtained from an LL leprosy pa- tient, M. leprae were found in macrophages as well as in smooth muscle cells and keratinocytes, suggesting that the skin is a potential route of leprosy transmis- sion (Satapathy et al. 2005). Keratinocytes also spon- taneously express CD80 (B7–1) on their surface. A reduction of CD80 surface expression also occurs on monocytes after LPS exposure during hypoxia (Lahat et al. 2003). Moreover, Nickoloff et al. reported that keratinocytes can regulate T cells through both cyto- kine expression and CD80 and CD28 interactions (Nickoloff et al. 1995).
bolic, and immunological factors, represent important mechanisms of defense too, by influencing the efficiency of the immuneresponse. A combination of phys- ical (such as an epithelial barrier), chemical (such as mucoid and protein secretions), and immu- nological defenses (such as tis- sue-resident macrophages and DCs) is particularly active at sites where injury and/or infections pose the greatest threat — organs that are exposed to the external environment, such as the skin, gut, lungs, and genito-urinary tract. In general, the initial host response to a pathogen is rapidly generated by the innate immune system, and this response often leads to the successful elimina- tion of the microorganism. This rapid response system largely depends on a sophisticated array of pattern recognition recep- tors (PRRs), which recognize conserved pathogen-associated molecular patterns (PAMPs) (34). Three major families of PRRs have been discovered: intracellular and extracellular TLRs (35, 36), intracellular nucleotide-binding oligomerization domain–like receptors (NLRs) (37), and intracellular retinoic acid–inducible gene I (RIG-I) receptors (38). Many cells of the immune system, including macrophages, T cells, eosinophils, B cells, DCs, NK cells, mast cells, and neutrophils, express PRRs, but these recep- tors have also been detected in structural cells such as fibroblasts, epithelial cells, and adipocytes (39). PAMPs include pathogen byproducts such as lipoproteins and lipopeptides, peptidoglycans, lipoteichoic acid, LPS, double-stranded RNA, flagellin proteins, and hypomethylated DNA (15, 37, 40). More recently, it has been shown that TLRs can also recognize endogenous proteins that have been modified by oxidation or nitration (41) as well as heat shock proteins that are released during acute inflammation and from damaged or dying cells (42). It is plausible that the coop- eration of several PRRs in the recognition of PAMPs initiates the first line of defense against infection and/or injury, including the production of proinflammatory cytokines, the synthesis of chemotactic cytokines that recruit cells of the immune system, enhanced phagocytosis, and the release of antimicrobial peptides (36). The intricate interactions between the host and pathogen dictate the natural history of many infectious diseases, and the persistence of many infectious pathogens is a consequence of the ability of these microorganisms to modulate the immuneresponse through various ingenious effector mechanisms (36). The failure to clear the pathogen and/or its byproducts consequently provides a persistent source of tissue injury and chronic inflammation. This results in fibrosis, which is therefore an undesirable outcome of an overactive innate immune system.
Although the impact of tumor immunology on the clinical management of most cancers is still negligible, there is increasing evidence that anticancer immune responses may contribute to the control of cancer after conventional chemotherapy. Thus, radiotherapy and some chemotherapeu- tic agents, in particular anthracyclines, can induce specific immune responses that result either in immunogenic cancer cell death or in immunostimulatory side effects. This anticancer immuneresponse then helps to eliminate residual cancer cells (those that fail to be killed by chemotherapy) or maintains micrometastases in a stage of dormancy. Based on these premises, in this Review we address the question, How may it be possible to ameliorate conventional therapies by stimulating the anticancer immuneresponse? Moreover, we discuss the rationale of clinical trials to evaluate and eventually increase the con- tribution of antitumor immune responses to the therapeutic management of neoplasia.
Experimental studies using mice indicated that higher numbers of mast cells were found in the small intestine of the infected mice after the infection was eliminated. Finally, data indicated that IL-6 is not necessary for the production of mast cell mediators such as histamine and MMCP-1 but instead suggest that IL-6 production by mast cells is an important element of the immuneresponse to Giardia (38-41).
Stem cell transplantation is a potential curative treatment for degenerative diseases of the retina. Among cell injection sites, the subretinal space (SRS) is particularly advantageous as it is maintained as an immune privileged site by the retinal pigment epithelium (RPE) layer. Thus, the success of subretinal transplantation depends on maintenance of RPE integrity. Moreover, both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) have negligible immunogenicity and in fact are immunosuppressive. Indeed, many studies have demonstrated that immunosuppressive drugs are not necessary for subretinal transplantation of stem cells if the blood-retinal barrier is not breached during surgery. The immunogenicity of induced pluripotent stem cells (iPSCs) appears more complex, and requires careful study before clinical application. Despite low rates of graft rejection in animal models, survival rates for ESCs, MSCs, and iPSCs in retina are generally poor, possibly due to resident microglia activated by cell transplantation. To improve graft survival in SRS transplantation, damage to the blood-retinal barrier must be minimized using appropriate surgical techniques. In addition, agents that inhibit microglial activation may be required. Finally, immunosuppressants may be required, at least temporarily, until the blood-retinal barrier heals. We review surgical methods and drug regimens to enhance the likelihood of graft survival after SRS transplantation.
Pathological hallmarks in the brain associated with epilepsy include imbalance in synaptic transmission, neuronal damage, and an exaggerated immuneresponse [2–6]. During the acute innate immuneresponse in the brain following seizures, microglia release pro- and anti- inflammatory mediators , undergo phenotypic changes, and migrate towards the epileptic foci where they phagocytize cell debris [8, 9]. Moreover, astrocytes change their activity state and exhibit disturbed buffering capacity of ions and glutamate uptake . In addition to the in- nate immune reaction, seizures may cause blood-brain barrier dysfunction and activation of vascular-associated and blood-derived immune cells . Hitherto, a seizure- induced immuneresponse has primarily been described within the epileptic foci of the brain, such as in hippocam- pal sclerosis in medial temporal lobe epilepsy, the most common form of epilepsy . However, recent findings support the idea that seizures may be viewed as a disturb- ance of entire brain networks, including subcortical nodes for seizure propagation . More remote areas of the brain, such as the retina, have not yet been investigated at all. Recently, we reported microglial activation in both cortical and subcortical brain areas even before behavioral seizures had developed in a genetic mouse model of epi- lepsy . Therefore, the relationship between brain in- flammation and epileptogenesis may also be further understood by studying the immuneresponse in remote areas to the epileptic foci that are not known to either generate or propagate seizures.