Humoral Defense System Research Articles

Antimicrobial Peptides: Principal Defense Constituents of Silk Worms - A Review

Insect has a highly developed innate immune system consisting of cellular and humoral responses. Antimicrobial peptides (AMPs) are the important components of the insect’s humoral defense system and were first purified from the giant silk moth, Hyalophora cecropia L (Boman et al., 1980). For a variety of infections, they serve as the initial line of defense. AMPS are low molecular weight peptides and generally cationic in nature. Off late, the resistance of the pathogenic microbes towards established antibiotics have become a serious threat to global health. Over the years, an array of AMPs from natural sources has served as potent candidate against various infective agents viz. bacteria, fungi and viruses. These insect peptides not only exhibit antibacterial action by rupturing the microbial membrane but also prevent the development of drug resistance by microbes. Studies have shown AMPS to have synergistic effects with traditional antibiotics, providing an opportunity for combined therapy. Defensin, cecropins, drosocin, attacins, diptericins, ponericins, metchnikowins and melittin are a few classes of AMPs from insects that are currently isolated. However, the possibility of discovering new AMPs cannot be fully ruled out. Currently, 33 peptides are undergoing clinical trials, and 43% of the 77 AMPs are still in the preclinical stage (Makwana et al., 2023). Daptomycin and ovitavancin are two antibacterial lipopeptides that Food and Drug Administration has recently approved that are used for skin infection caused by bacteria. The present paper is an attempt to provide a comprehensive insight on antimicrobial peptides isolated from silk worm with reference to their structures, functions and possible mechanism of action.

Engraving our first B cell memories into the repertoire

Memory B cells are central to effective protection against reinfection. Glaros et al. used single-cell techniques to illuminate how activated mouse B cells are diverted into forming memory cells a few days post-immunogenic exposure. Early memory subsets contribute to a crucial goal: building a diverse and agile humoral defense system.

Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking

Complement is an enzymatic humoral pattern-recognition defence system of the body. Non-specific deposition of blood biomolecules on nanomedicines triggers complement activation through the alternative pathway, but complement-triggering mechanisms of nanomaterials with dimensions comparable to or smaller than many globular blood proteins are unknown. Here we study this using a library of <6 nm poly(amido amine) dendrimers bearing different end-terminal functional groups. Dendrimers are not sensed by C1q and mannan-binding lectin, and hence do not trigger complement activation through these pattern-recognition molecules. While, pyrrolidone- and carboxylic acid-terminated dendrimers fully evade complement response, and independent of factor H modulation, binding of amine-terminated dendrimers to a subset of natural IgM glycoforms triggers complement activation through lectin pathway-IgM axis. These findings contribute to mechanistic understanding of complement surveillance of dendrimeric materials, and provide opportunities for dendrimer-driven engineering of complement-safe nanomedicines and medical devices.

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study.

Tonsil tissue is a very important component of the human immunity system, contributing to the functioning of the cellular and humoral defence system, especially in childhood. The endoplasmic reticulum (ER) is an organelle that has a very important function in the balanced functioning of cells, in which the accumulation of a cellular protein called ER stress occurs in case of dysfunction. ER stress influences the pathogenesis of many diseases and immune system functions. We aimed to investigate the relation between the diseases of tonsil tissue and ER stress response to elucidate the mechanisms of diseases related with the immune system. A prospective study was conducted in 46 children aged between 2 and 16years who underwent tonsillectomy for chronic tonsillitis or tonsillar hypertrophy. Tonsil tissue was separated into two groups according to their size and evaluated in terms of ER stress markers and apoptosis markers by Real-time PCR and Western blot analysis. The ΔCT levels of ER stress markers (ATF4, ATF6, CHOP, GRP78, EIF2AK3, ERN1, GRP94) were greater in children with chronic tonsillitis (p < 0.005). In contrast, the tonsillar hypertrophy group had greater ΔCT levels of apoptosis markers (BAX, BCL-2) according to the Real-time PCR method (p < 0.005). According to the Western blot analysis, the normalized levels of ATF4, ATF6, CHOP, GRP78, and ERN1 genes were found greater in the chronic tonsillitis group than the tonsillar hypertrophy group. There was no difference between the two groups in terms of normalized BCL-2 and BAX levels by Western blot analysis. This is the first study in the literature investigating the effect of the ER stress pathway on the etiopathogenesis of tonsil diseases. It was concluded that the ER stress pathway plays a role in the etiopathogenesis of chronic tonsillitis. Investigating the relationship between ER stress and structures such as the tonsil tissue that make up the immune system can help create new treatment strategies. Trial Registration ClinicalTrials.gov Identifier: NCT04653376.

A Comprehensive Review on Crustaceans' Immune System With a Focus on Freshwater Crayfish in Relation to Crayfish Plague Disease.

Freshwater crayfish immunity has received great attention due to the need for urgent conservation. This concern has increased the understanding of the cellular and humoral defense systems, although the regulatory mechanisms involved in these processes need updating. There are, however, aspects of the immune response that require clarification and integration. The particular issues addressed in this review include an overall description of the oomycete Aphanomyces astaci, the causative agent of the pandemic plague disease, which affects freshwater crayfish, and an overview of crustaceans’ immunity with a focus on freshwater crayfish. It includes a classification system of hemocyte sub-types, the molecular factors involved in hematopoiesis and the differential role of the hemocyte subpopulations in cell-mediated responses, including hemocyte infiltration, inflammation, encapsulation and the link with the extracellular trap cell death pathway (ETosis). In addition, other topics discussed include the identity and functions of hyaline cells, the generation of neoplasia, and the emerging topic of the role of sessile hemocytes in peripheral immunity. Finally, attention is paid to the molecular execution of the immune response, from recognition by the pattern recognition receptors (PRRs), the role of the signaling network in propagating and maintaining the immune signals, to the effector elements such as the putative function of the Down syndrome adhesion molecules (Dscam) in innate immune memory.

Infusion Reactions Associated with the Medical Application of Monoclonal Antibodies: The Role of Complement Activation and Possibility of Inhibition by Factor H.

Human application of monoclonal antibodies (mAbs), enzymes, as well as contrast media and many other particulate drugs and agents referred to as “nanomedicines”, can initiate pseudoallergic hypersensitivity reactions, also known as infusion reactions. These may in part be mediated by the activation of the complement system, a major humoral defense system of innate immunity. In this review, we provide a brief outline of complement activation-related pseudoallergy (CARPA) in general, and then focus on the reactions caused by mAb therapy. Because the alternative pathway of complement activation may amplify such adverse reactions, we highlight the potential use of complement factor H as an inhibitor of CARPA.

Histopathological and combinatorial effects of the metalloprotease InhA1 and Cry proteins of Bacillus thuringiensis against Spodoptera littoralis

The zinc metalloprotease (InhA) of Bacillus thuringiensis specifically hydrolyzes cecropins and attacins, two antibacterial peptides in the immune hemolymph of insects, leading to a high resistance of the bacteria to the humoral defense system of its host. In the present study, the inhA gene of B. thuringiensis strain BUPM28 was cloned and the nucleotide sequence analysis revealed that it was identical to that of B. thuringiensis 8010. The expressed InhA1 protein in Escherichia coli showed toxicity to neonate Spodoptera littoralis larvae with a LC50 of 2.07±0.72μg/cm2. Study of the effect of combining Cry proteins with InhA1 showed that one improves the toxicity of the other one against S. littoralis. Investigation of the histopathological effect of this metalloprotease showed an extensive damage of S. littoralis epithelium tissue. These results provide an insight to the use of InhA as supplement to Cry toxins to improve the efficacy of B. thuringiensis formulations and to overcome possible resistance problems.

Molecular Characterization and Phylogenetic Analysis of Novel Isoform of Anti-lipopolysaccharide Factor from the Mantis Shrimp, Miyakea nepa.

Anti-lipopolysaccharide factor (ALF) is a cationic anti-microbial peptide representing humoral defence system exhibiting a diverse spectrum of activity against microbial pathogens, including gram-negative and gram-positive bacteria, fungi, parasites and viruses. In this study, we identified and characterized a novel ALF homologue (MnALF) encoding cDNA sequence from the haemocytes of stomatopod mantis shrimp Miyakea nepa. The deduced peptide of MnALF encoded for a 123-amino acid peptide with a 25-residue signal peptide containing selenocysteine followed by a highly cationic mature peptide comprised of a putative LPS-binding domain flanked by two cysteine residues. BLAST analysis of MnALF showed that it exhibits identity to crustacean and limulid ALFs. The mature peptide of MnALF has a net charge of +7 and predicted molecular weight of 10.998kDa with a theoretical isoelectric point (pI) of 9.93. Spatial structure of MnALF comprises three α-helices packed against a four-stranded β-sheet of which two were linked by a disulphide bond to form an amphipathic loop similar to the structure of Penaeus monodon, ALF-Pm3. All these features suggest that MnALF could play an imperative role in the innate defence mechanism of M. nepa. To our knowledge, this study accounts for the first report of an anti-microbial peptide from the order stomatopoda.

Autacoids in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis (UC), are complex disorders characterized by chronic, local and systemic inflammation and spontaneously relapsing course. The causes of these diseases are unknown, however they display genetic and environmental components and appear to be immunologically mediated in part by enteric microbiota [1]. The immune system cells activation may lead to activation of plasma proteolytic cascades [1,2], as well as to release of inflammatory mediators in inflamed intestine. There are convincing evidences that IBD are diseases of immunological hyperresponsiveness within the mucosa. Immunological reactions may be directed against luminal bacteria and their products normally present in the intestine [2]. Both innate and adaptive immune response play a role in IBD pathogenesis and possibly in etiology. Autacoids, a local hormones e.g., histamine, serotonin, kinins, angiotensin, eicosanoids, neurotensin, nitric oxide, endothelins may be produced and act locally in IBD – inflamed intestine, and play a role inflammatory response, and progression in both Crohn’s disease and UC. A role of eicosanoids and nitric oxide in IBD was relatively well delineated. Much less attention has been paid to other autacoids, although a significance of the intestinal tissue kallikrein – kinin system in IBD has been investigated in the late 1990s – 2000s. Histamine, serotonin and kinins are vasodilator autacoids which as part of the humoral defense system participate in the inflammatory response. Enterochromaffin cellwhich are present in the mucosa of all regions of the gut except the oesophagus, contain most of the body’s serotonin (5-HT). Derived serotonin (5-HT) express toll-like receptors and thus may detect microorganisms [3,4]. Enterochromaffin cell 5-HT also appears to contribute to the initiation of intestinal inflammation, at least in the animal models. Mice that lack the 5-HT transporter (SERT; SERTKO mice), which inactivates 5-HT, are sensitive to experimentally induced colitis especially in animals with interleukin (IL)-10 deletion [5,6]. Histamine as a proinflammatory mediator is selectively located in the granules of human mast cells and basophils and released from these cells upon degranulation. It was shown that the number of mast cells and mast cells tryptase expression (a marker of mast cell degranulation are increased in colonic mucosa and submucosa in experimental and human IBD [7]. Interestingly, mast cells originated from the resected colon of active Crohn’s disease or UC released more histamine than those from normal colon after stimulation with colon-derived murine epithelial cell-associated compounds [8]. Knutson et al. found that the histamine secretion was increased in patients with Crohn’s disease compared with normal controls, and the secretion of histamine was related to disease activity, indicating strongly that degranulation of mast cells was involved in active Crohn’s disease [9]. A significance kinins in human IBD is still underestimated although in animal IBD models kinins have been documented in part to mediate intestinal and systemic inflammation. Tissue kallikrein cleaves kininogens to release kinins. The importance of intestinal tissue kallikrein (ITK) in the intestine mainly depends upon the secretion of active enzyme in the presence of kininogens, especially low molecular weight kininogen (LK), with subsequent kinins generation. It should be noted that in mild insults, kinins may play a salutary role recruiting to the extravascular milieu proteases, acute phase proteins, and neutrophils. In severe inflammation, however, kinins amplifies the inflammatory cascade, and contributes to tissue destruction. In late 1990s we have focused our attention on the ITK-kinin system in IBD. To study the localization of ITK and its naturally occurring serine protein inhibitor (SERPIN), kallistatin, in IBD we first focused in our models of rats enterocolitis induced by proteoglycan-polysaccharide (PG-APS) closely resembling Crohn’s disease [10]. We showed that the normal location of ITK was the goblet cells and that substantial amounts of ITK were present in the macrophages of the granuloma found in the submucosa, suggesting that ITK is present at the site of inflammation. In addition, ITK was found to be lower in the supernatant from in vitro cultures of inflamed intestine. This combination suggested secretion of ITK during inflammation.

T. brucei Infection Reduces B Lymphopoiesis in Bone Marrow and Truncates Compensatory Splenic Lymphopoiesis through Transitional B-Cell Apoptosis

African trypanosomes of the Trypanosoma brucei species are extracellular protozoan parasites that cause the deadly disease African trypanosomiasis in humans and contribute to the animal counterpart, Nagana. Trypanosome clearance from the bloodstream is mediated by antibodies specific for their Variant Surface Glycoprotein (VSG) coat antigens. However, T. brucei infection induces polyclonal B cell activation, B cell clonal exhaustion, sustained depletion of mature splenic Marginal Zone B (MZB) and Follicular B (FoB) cells, and destruction of the B-cell memory compartment. To determine how trypanosome infection compromises the humoral immune defense system we used a C57BL/6 T. brucei AnTat 1.1 mouse model and multicolor flow cytometry to document B cell development and maturation during infection. Our results show a more than 95% reduction in B cell precursor numbers from the CLP, pre-pro-B, pro-B, pre-B and immature B cell stages in the bone marrow. In the spleen, T. brucei induces extramedullary B lymphopoiesis as evidenced by significant increases in HSC-LMPP, CLP, pre-pro-B, pro-B and pre-B cell populations. However, final B cell maturation is abrogated by infection-induced apoptosis of transitional B cells of both the T1 and T2 populations which is not uniquely dependent on TNF-, Fas-, or prostaglandin-dependent death pathways. Results obtained from ex vivo co-cultures of living bloodstream form trypanosomes and splenocytes demonstrate that trypanosome surface coat-dependent contact with T1/2 B cells triggers their deletion. We conclude that infection-induced and possibly parasite-contact dependent deletion of transitional B cells prevents replenishment of mature B cell compartments during infection thus contributing to a loss of the host's capacity to sustain antibody responses against recurring parasitemic waves.

Alteration of antioxidant defense status precedes humoral immune response abnormalities in macrosomia

SummaryBackgroundThis study aimed to investigate whether the anomalies affecting the antioxidant and humoral immune defenses could start at birth and to check whether the decrease in antioxidant defenses may precede the immune abnormalities in macrosomic newborns.Material/MethodsThirty macrosomic and 30 sex-matched control newborns were recruited for a retrospective case-control study at the Maghnia Maternity Hospital of Tlemcen Department (Algeria).ResultsThe serum IgG levels were similar in both groups. However, plasma ORAC, albumin, vitamin E, SOD, CAT and GSH-Px levels were significantly decreased in macrosomic as compared to control newborns, yet no difference was observed after adjustment for weight. Additionally, serum concentrations of complement C3, MDA and XO were significantly higher in macrosomic as compared to controls before adjustment for weight. Moreover, macrosomia was significantly associated with high levels of complement C3 (OR=8, p=0.002); whereas no association with those of IgG was observed (OR<1, p>0.05). Furthermore, macrosomia was significantly associated with low levels of ORAC (OR=4.96, p=0.027), vitamin E (OR=4.5, p=0.018), SOD (OR=6.88, p=0.020) and CAT (OR=5.67, p=0.017), and with high levels of MDA (OR=10.29, p=0.005).ConclusionsAbnormalities of the humoral defense system in excessive weight could be preceded by alterations of the anti-oxidative defense and by inflammatory response and activation of innate immunity at birth. Additionally, excessive weight could be a potential factor contributing to decreased anti-oxidative capacity and increased oxidative stress.

Modulation of the immune system by Boswellia serrata extracts and boswellic acids

Extracts from the gum resin of Boswellia serrata and some of is constituents including boswellic acids affect the immune system in different ways. Among the various boswellic acids 11-keto-beta-boswellic acid (KBA) and acetyl-11-keto-beta-boswellic acid have been observed to be active. However, also other boswellic acids may exhibit actions in the immune system. In the humoral defence system a mixture of boswellic acis at higher doses reduced primary antibody titres; on the other hand lower doses enhanced secondary antibody titres following treatment with sheep erythrocytes. In the cellular defence boswellic acides appear to increase lymphocyte proliferation whereas higher concentrations are even inhibitory. Moreover, BAs increase phagocytosis of macrophages. BAs affect the cellular defence system by interaction with production/release of cytokines. Thus, BAs inhibit activation of NFkappaB which is a product of neutrophile granulocytes. Consequently a down regulation of TNF-alpha and decrease of IL-1, IL-2, IL-4, IL-6 and IFN-gamma, which are proinflammatory cytokines by BEs and BAs has been reported. Suppressions of the classic way of the complement system was found to be due to inhibition of the conversion of C3 into C3a and C3b. However, which of these pharmacological actions contribute to the therapeutic effects and which is finally the best dosage of a standardized extract needs further examination. And it is also a question whether or not a single BA will have the same therapeutic effect as a standardized extract. Among the mediators of inflammatory reaction, mast cell stabilisation has been described by a BE. Inhibition of prostaglandin synthesis appears to play only a minor role as far as the anti-inflammatory effect is concerned. On the other hand the inhibitory action of BAs on 5-LO leading to a decreased production of leukotrienes has received high attention by the scientific community since a variety of chronic inflammatory diseases is associatied with increased leukotriene activity. At the end of the cascade of events in the cellular immune system as far as it directs to various tissues of the body - i.e. autoimmune diseases - formation of oxygen radicals and proteases (for example elastase) play an important destructive role. Here, BEs as well as BAs have been found to be inhibitory. From the pharmacological properties of BEs and BAs it is not surprising that positive effects of BEs in some chronic inflammatory diseases including rheumatoid arthritis, bronchial asthma, osteoarthritis, ulcerative colitis and Crohn's disease have been reported.

Antimicrobial peptides from marine invertebrates as a new frontier for microbial infection control

Antimicrobial peptides are widely expressed in organisms and have been linked to innate and acquired immunities in vertebrates. These compounds are constitutively expressed and rapidly induced at different cellular levels to interact directly with infectious agents and/or modulate immunoreactions involved in defense against pathogenic microorganisms. In invertebrates, antimicrobial peptides represent the major humoral defense system against infection, showing a diverse spectrum of action mechanisms, most of them related to plasma membrane disturbance and lethal alteration of microbial integrity. Marine invertebrates are widespread, extremely diverse, and constantly under an enormous microbial challenge from the ocean environment, itself altered by anthropic influences derived from industrialization and transportation. Consequently, this study reexamines the peptides isolated over the past 2 decades from different origins, bringing phyla not previously reviewed up to date. Moreover, a promising novel use of antimicrobial peptides as effective drugs in human and veterinary medicine could be based on their unusual properties and synergic counterparts as immune response humoral effectors, in addition to their direct microbicidal activity. This has been seen in many other marine proteins that are sufficiently immunogenic to humans, not necessarily in terms of antibody generation but as inflammation promoters and recruitment agents or immune enhancers.

Characterization of crustins from the hemocytes of the spider crab, Hyas araneus, and the red king crab, Paralithodes camtschaticus

Crustins are distributed across the decapods and are believed to play a significant part in the humoral defense system of their host. In this study, two crustin isoforms from Hyas araneus hemocytes were purified and tested for antimicrobial activity against selected microorganisms. They show both antibacterial and antifungal activity, with highest activity against the Gram-positive bacteria Corynebacterium glutamicum. Sequencing of the transcripts showed them to have a mature peptide of 90 amino acids and differing in three positions in the mature peptide. They were named Cru Ha1 and Cru Ha2. Real-time RT-PCR revealed that they mainly are expressed in hemocytes. Screening a cDNA library detected a crustin sequence in Paralithodes camtschaticus hemocytes, coding for a mature peptide of 98 amino acids. It was named Cru Pc. Based on phylogenetic inference and primary structure, Cru Ha1 and Cru Ha2 were placed within the Type I group of crustins, while Cru Pc belongs to the Type II.

Local defense systems in the prepuce

Urinary tract infection (UTI) is a common bacterial infection in children. Circumcision reduces the incidence of UTI, and prevents preputial colonization with uropathic bacteria in childhood. However, there is insufficient information about the reason(s) why such colonization tends to occur in prepucium skin. We evaluated some of the humoral and cellular defense systems in the prepucium skins of 30 boys (age range 6 months to 5 years). We measured the expressions of Langerhans cells, mast cells, T lymphocytes, IgA, IgG and IgM in the prepuce and compared them with those in normal skin. Tissues obtained during circumcision were divided into two groups. In the first group, sections were stained with hematoxylin-eosin and toluidine blue. Immunohistochemical reactions were performed on paraffin-embedded tissue by means of the avidin-biotin-peroxidase complex method. The antibodies used were S-100 for Langerhans cells and CD8 and CD4 for T lymphocytes. In the second group, frozen sections were stained for IgA, IgG and IgM using an immunofluorescence method. The distribution of mast cells and IgG positivity was similar to that of normal skin. Langerhans cells were increased in prepucium skin (p<0.05), whilst only a few CD4 T lymphocytes were observed around the perivascular area and no expression of CD8 was observed in the prepucium and normal skin. The increase in Langerhans cells in prepucium skin may be the result of continuous stimulation of bacteria found in the periurethral area, and the absence of CD8 may help the colonization of uropathic bacteria.

Persistent synovitis in two children with Lyme arthritis linked with HLA-DRB1*1104

In the past 20 years Lyme disease (LD; also known as Lyme borreliosis) has emerged to become the most common tickborne diseases in the northern hemisphere. The natural history and the clinical course of this unusually varied human infection poses a variety of problems for the patient, the clinician, the microbiologist and the immunologist. The manner in which individuals react to the offending microorganism is diverse but at the same time specific at the individual level. Many people develop immunity against the tick without any sign of disease. Others develop a disease that evolves into different stages, which tends to relapse and then ultimately to develop into a chronic disease. Only some of its many organ manifestations correspond to a clinical entity. Also, there seems to be an agedependent pattern to the course of the disease. Most children with Lyme arthritis (LA) develop acute or episodic arthritis, but a minority will present long-lasting arthritis. Borreliae can survive in infected persons despite all the efforts of the humoral immune defense system, resulting in relapses, late manifestations, and chronic courses. It is tempting to address the question of why the immune response becomes or is inappropriate. Is there an immunogenetic basis for an altered or pathologic immune response? Can we find any parallelism with other organ-specific diseases? We recently reported two cases of patients with persistent LA [4] who were investigated within the framework of a recently proposed hypothesis [6] that “patients with persistent LA have not been shown to have an increased frequency of the HLA-B27 allele, as in reactive arthritis, or the HLA-DRB1*0801 or HLA-DRB1*1l alleles, as in pauciarticular JRA”. As we reported earlier [4], HLA-27 was absent in both children. None of both patients had the MHC II allele DRB*041, linked with the candidate auto-antigen human leucocyte function-associated antigen 1 (hLFA-1 orCD11a). To our surprise, both patients [4] shared the same MHC II allele DRB1*11, despite the fact that there was no consanguinity. One of the patients was, 3 years prior to the tick-bite, diagnosed with an early onset oligoarticular juvenile idiopathic arthritis (oJIA ) of the left knee from which she was considered to have completely recovered. Both children are of Caucasian origin, but they contracted LD in different parts of the world (USA and Belgium). The causal strains were different. In persistent LA, histologic and immunobiologic features point in the direction of an autoimmune disease which − with respect to symptoms and findings − resemble oJIA. Our first patient was known to have oJIA in remission. The concept of a self-protein or epitope-peptide and a foreign protein or epitope-peptide as a trigger for autoreactive T cells is an interesting model of the disease, possibly elicited by certain MHC alleles, especially DR alleles, as demonstrated by Steere in adolescent and adult patients [6]. Molecular mimicry has been proposed. As oJIA patients have been linked to a different immunogeG. Hendrickx (*) . Y. Vandenplas Department of Paediatrics, Paediatric Orthopaedic and Rheumatology Unit, Academisch Ziekenhuis -Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium e-mail: g.hendrickx@st-anna.nl Tel.: +32-2-4775781 Fax: +32-2-4775786

Tissue and plasma kallikrein in inflammatory bowel disease

Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are characterised by local (mainly intestinal) and systemic inflammation. The diseases are idiopathic, but display genetic and environmental components [1]. They appear to be mediated by the activation of immune system and plasma proteolytic cascades. The kallikrein–kinin system is a part of humoral defence system and participates in the inflammatory response.

Impact of different environmental factors on the circulating immunoglobulin levels in the Nile tilapia, Oreochromis niloticus

Immunoglobulin M (IgM) in teleost fishes is the only component of the specific humoral defense system that is affected by environmental factors. In the present study, we examined the effect of various environmental factors (water temperature, salinity, pH and suspended solids) on the plasma IgM in the Nile tilapia, Oreochromis niloticus. For all treatments, fish were acclimatized in particular environmental conditions for 2 or 4 weeks. For fish reared at 18.4, 23 and 28 °C, the circulating IgM concentration increased with increased water temperature for 2 weeks. Rearing the fish at 33 °C resulted in a decrease in IgM concentration, suggesting that the fish possess an appropriate thermal range for production of immune substances. Plasma level of IgM increased significantly with salinity at 12 and 24 parts per thousand (ppt). On the other hand, plasma IgM concentration did not change by exposing the fish to acidification (pH 4.0) and suspended solids (20, 200, and 2000 mg/l). These results suggest that the specific immune system of tilapia changes by certain factors in aquatic environment.

Trichuris suis: Detection of Antibacterial Activity in Excretory-Secretory Products from Adults

Abner, S. R., Parthasarathy, G., Hill, D. E., and Mansfield, L. S. 2001. Trichuris suis: Detection of antibacterial activity in excretory-secretory products from adults. Experimental Parasitology99, 26–36. Antibacterial activity was detected in excretory-secretory products (ESP) of adult Trichuris suis cultured in vitro in serum-free media. Gram-negative bacteria (Campylobacter jejuni, Campylobacter coli, and Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) were sensitive to ESP. Susceptibility was dependent on the concentration of ESP but not on the inoculum size. Preliminary assessment of the mode of action suggests a bacteriocidal mechanism. This antibacterial activity was heat stable and resistant to digestion with pronase E and trypsin. Based on ultrafiltration experiments, the activity is less than 10,000 MW. This excreted/secreted antibacterial activity from T. suis is likely a component of a humoral defense system for this helminth.

Veno-venous bypass in liver transplantation: heparin-coated perfusion circuits reduce the activation of humoral defense systems in an in vitro model.

We studied the effects of bypass circuit surface heparinization on kallikrein-kinin, coagulation, fibrinolytic and complement activation in a closed model system for simulating veno-venous bypass (WBP) in orthotopic liver transplantation (OLT). The circuits were identical to those in routine use during clinical OLT in our institution. Fresh whole human blood diluted 1:2 with Ringer's acetate was circulated at a non-pulsatile flow (2 l/min) and at a constant temperature (37.5 degrees C) for 12 h. In 10 experiments, the entire inner surface of the circuits was coated with end-point attached heparin (HC). In the remaining 10, non-treated PVC tubing was used (NC). Components of the plasma kallikrein-kinin, coagulation, fibrinolytic and complement systems were analyzed using functional techniques (chromogenic peptide substrate assays) and enzyme immunoassays at baseline, 3 and 12 h. Significant activation of the initial (C3bc) and terminal (TCC) components of the complement system were found in both the NC and HC groups after 3 and 12 h: C3bc: NC: baseline = 4 (3.5-7.7), 3 h = 17.3* (12.5-27), 12h = 31* (17.7-63.6), HC: baseline = 4.9 (3.2-6.8), 3h = 9* (6-14.4), 12h = 13.7* (7.4-18.1). TCC: NC: baseline = 0.4 (0.2-0.6), 3h = 5*(0.8-11.9), 12 h: 13.1* (4.2-25.7). HC: baseline = 0.5 (0.1-0.6), 3 h = 0.6* (0.1-0.8), 12 h = 1.2* (0.3-2) AU/ml; median and range (*: p < 0.05). The C3bc and TCC concentrations were significantly higher in the NC group at 3 and 12 h, compared to the HC group: C3bc (NC vs. HC group): 3 h, p < 0.001; 12 h, p < 0.001. TCC (NC vs. HC group): 3h, p < 0.001; 12 h, p < 0.001. Significant increases in the values of thrombin-antithrombin complexes (p = 0.003), prothrombin fragment 1 + 2 (p = 0.006) and plasmin-alpha2-antiplasmin complexes (p = 0.016) were found in the non-coated group, but not in the heparin-coated group during the observation period, showing that the coagulation and fibrinolytic systems were activated in the non-coated circuits. We conclude that heparin-coating of the internal surface of the extracorporeal perfusion circuit used for WBP reduces activation of the plasma cascade systems in a closed venous system in vitro.