Innate Resistance Mechanisms Research Articles

The occurrence and mechanisms of innate immunity against parasites in fish

Parasitic infections in teleost fish are limited by constitutive innate defence mechanisms that render the host refractory or reduce the severity of infection. Controlled challenge trials using naive animals provide indirect evidence of innate immunity as well as identifying the host range or specificity of a parasite, often when specific details of defence mechanism(s) are lacking. Examples of parasites for which innate immunity may be inferred from cross-infectivity studies include Gyrodactylus spp., Lepeophtheirus salmonis, Cryptobia spp., Trypanosoma spp., Ceratomyxa shasta, Myxobolus cerebralis and Kudoa thyrsites. Recent studies however, have begun to clarify the relative roles of innate and acquired immunity against parasitic infection in teleosts by recognizing the presence and significance of specific innate effector mechanisms. The physico-chemical characeristics of skin mucus, the presence of bioactive substances including lysozyme, complement, C-reactive protein, haemolysins and lectins and the epidermal migration of inflammatory cells and their secretions may affect the establishment and proliferation of ectoparasitic copepods, ciliates or monogenea. Similarly in refractory species, haematozoic parasites are lysed via the alternative complement pathway and in susceptible and refractory hosts, protease inhibitors associated with the plasma neutralize proteolytic virulence factors. Detailed knowledge of innate resistance mechanisms against histiozoic parasites are lacking although non-specific cytotoxic lymphoid cells and macrophages probably play a role. The demonstration in certain disease models that innate resistance traits are under genetic control and may be inherited in a simple Mendelian fashion suggests opportunities for selective breeding for resistance against parasitic disease. Beyond a small number of well-described models however, research programs focussing on innate immunity against parasites in fish are lacking. Given the relative importance of innate immunity in fish, particularly as disease losses continue to have an economic impact in aquaculture, this area deserves considerable attention.

Overview of host defense mechanisms in systemic mycoses and the basis for immunotherapy.

Host defense against systemic mycoses is multifactoral, depending on innate, as well as acquired, mechanisms. Innate resistance mechanisms include intact physical barriers, host proteins, nonspecific inflammatory responses, hormonal status, sex, and genetic make-up. However, the importance of any 1 factor in resistance to systemic fungal infections can vary depending on the causative agent. Macrophages and neutrophils play a critical role in the stasis or killing of these organisms by using the production of oxygen radicals, cationic proteins, nitric oxide (NO), and peroxides or iron deprivation. Although these cells are often ineffective in killing the organisms innately, activation of macrophages and neutrophils during an acquired immune response by the proinflammatory cytokine interferon-gamma as well as colony-stimulating factors increases the capacity of these cells for killing. A strong Th1 response can provide protective immunity, whereas a Th2 response can result in increased disease severity. The importance of native antibodies in resistance to mycoses remains in question.

Inducible expression of the long pentraxin PTX3 in the central nervous system

PTX3 is a prototypic long pentraxin consisting of a C terminal 203-amino acid pentraxin-like domain coupled with an N-terminal 178-amino acid unrelated portion. PTX3 is induced by primary proinflammatory signals in various cell types, most prominently macrophages and endothelial cells. Other long pentraxins, such as murine or rat neuronal pentraxin 1 (NP1) and human neuronal pentraxin 2 (NPTX2), are expressed in the central nervous system (CNS). The present study was designed to investigate whether PTX3 is expressed in the brain and to define the structures and cells involved. Intracerebroventricular (i.c.v.), but not i.v., injection of LPS induced high levels of PTX3 mRNA in the mouse brain. In contrast NP1 is constitutively expressed in the murine CNS and is not modulated by LPS administration. I.c.v. IL-1β was also a potent inducer of PTX3 expression in the CNS, whereas TNFα was substantially less effective and IL-6 induced a barely detectable signal. Central administration of LPS and IL-1 induced PTX3 also in the periphery (heart), whereas the reverse did not occur. Expression of PTX3 was also observed in the brain of mice infected with Candida albicans ( C. albicans) or Cryptococcus neoformans. ( C. neoformans). The kinetics of PTX3 gene induction were consistently different between C. albicans- and C. neoformans-infected mice, according to the diverse outcome of the CNS immune reaction. In situ hybridization revealed that i.c.v. injection of LPS induced a strong PTX3 expression in presumptive glial cells, in the white matter (corpus callosum, fimbria) and meningeal pia mater as well as in dentate gyrus hilus and granule cells. No constitutive expression of PTX3 was detected. Central expression of PTX3 may amplify mechanisms of innate resistance and damage in the CNS. The possibility of a direct interaction of PTX3 with neuronal cells, as suggested for NPTX2, remains to be explored.

Protective Antibodies and Anamnestic Response in Salvelinus fontinalis to Cryptobia salmositica and Innate Resistance of Salvelinus namaycush to the Hemoflagellate

Cryptobia-susceptible Salvelinus fontinalis vaccinated with a live Cryptobia salmositica vaccine were protected against C. salmositica and they were still protected 53 wk after their initial challenge. Parasites were lysed when they were incubated with immune plasma and complement and this confirms that complement-fixing antibody is an important part of the protective mechanism. Immunological memory was demonstrated in both vaccinated-challenged, and infected-recovered S. fontinalis as there were rapid and significant increases in complement-fixing antibody titers after parasite challenge. This indicates that S. fontinalis are capable of an anamnestic response. Most naive Salvelinus namaycush were not susceptible to C. salmositica infection, and their fresh plasma lysed C. salmositica under in vitro conditions. The lytic factor(s) was inactivated by heating the plasma prior to parasite incubation. This indicates that the alternate pathway of complement activation is likely the mechanism of innate resistance in S. namaycush.

Roles of the humoral response in coxsackievirus B-induced disease.

Antibodies to a coxsackie virus group B (CVB) may be regarded as a footprint record of trespass in an animal by one of these viruses that resulted in subsequent induction of a humoral immune response toward numerous immunogenic viral protein epitopes. These epitopes will be found in virion polypeptides, virion polypeptides in various stages of completion, nonstructural viral proteins required for replication and the latter proteins in stages of synthesis. Linear, conformational and combinatorial viral epitopes will stimulate production of anti-viral protein antibodies of several immunoglobulin classes and IgG subclasses. Natural challenges to humans by the CVB occur most frequently by ingestion from liquids or foods, contact with fingers or fomites, transplacental passage to the fetus and probably by aerosols during replication in the respiratory tract. The major outcomes of most CVB infections of humans are asymptomatic, but there are numerous transient infections that result in illnesses in the upper respiratory and gastrointestinal tracts and skin. Less frequently, CVB cause serious illnesses involving inflammatory responses in the heart, meninges, brain and pancreas that lead to chronic diseases, some of which terminate in death. To delineate parameters of infection involved in protection or in pathology, murine models of CVB-induced human diseases have been studied for nearly four decades. Reviews of studies on basic mechanisms involved in CVB-induced diabetes mellitus (Barrett-Conner 1985; Toniolo et al. 1988; D’alessio 1992) and in CVB3- and CVB2-induced myocarditis (Lerner and Wilson 1973; Woodruff 1980; Lerner 1985, Gauntt 1987; Gauntt et al. 1993a) show the value of these models in increasing our understanding of the contributions of innate resistance mechanisms and both humoral and cell-mediated immune systems to the resolution or continuation of disease.KeywordsHeart TissueViral MyocarditisCardiac MyosinCVB3 InfectionChronic MyocarditisThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Interleukin-12 and tumor necrosis factor alpha mediate innate production of gamma interferon by group B Streptococcus-treated splenocytes of severe combined immunodeficiency mice

The existence of interleukin-12-mediated innate immune responses to group B streptococci (GBS) was tested by examining T-lymphocyte-independent gamma interferon (IFN) production in cultured splenocytes from severe combined immunodeficiency mice. Splenocytes were cultured with killed or living GBS for 48 h, and then IFN was measured by enzyme-linked immunosorbent assay. Type III GBS as well as other extracellular bacterial agents of neonatal sepsis (staphylococci and enterococci) induced IFN production, which was enhanced by interleukin-2 and was inhibited by neutralizing antibodies to tumor necrosis factor alpha and to mouse interleukin-12. Interleukin-12 bioactivity was present in conditioned medium from GBS-treated adherent macrophages. Adherent peritoneal macrophages and bone marrow-derived natural killer cells from severe combined immunodeficiency mice cultured separately with GBS did not produce IFN, whereas cocultures did produce IFN. Functional macrophage activation was evident by nitric oxide production in GBS-treated splenocyte cultures. The results show that extracellular pathogens such as GBS, similarly to intracellular microbes, induce macrophage interleukin-12 and tumor necrosis factor alpha, which promote natural killer cell secretion of IFN, which then enhances innate phagocyte resistance mechanisms.

Genetic resistance to coronavirus infection. A review.

Much information on the mechanisms of host genetic resistance to viral infections has come from research on the coronaviruses, particularly on the mouse hepatitis viruses (MHV). One of the fundamental observations made by Bang and co-workers some thirty years ago was that MHV infection of the host proceeds in a series of stages, which can be seen as three sequential barriers of host resistance1–3. These stages have also become the key to dissecting the genetic control of host resistance to coronaviruses. The first stage is the presence or absence of a specific cellular receptor which controls viral entry. Once the virus has gained entry, factors expressed by the host cells will then restrict or permit viral growth and acute disease. Finally, the humoral and cellular defenses of the host’s immune system will determine whether the virus is eliminated or disseminated and a chronic disease is established. In this chapter, we have organized our review of genetic resistance to coronaviruses according to these three host resistance mechanisms: genetic control at the level of cellular receptors, genetic control at the level of the macrophage, and genetic control at the level of acquired immunity. However, we would like to stress that these ‘levels’ are purely operational boundaries. In reality, a host can be infected with a virus several times during its lifetime, and thus all available innate and immune resistance mechanisms will be called into play at once. In addition, we have included a general outline of the methods used to identify host resistance genes in mouse models of infection. Those interested in a more complete explanation of genetic analysis can refer to recent articles on this subject4,5.

Immune responses to Yersinia enterocolitica in susceptible BALB/c and resistant C57BL/6 mice: an essential role for gamma interferon.

Susceptibility of mice to infection with Yersinia enterocolitica has been shown to be related to neither the Ity locus encoding for resistance to Salmonella typhimurium and other pathogens nor the H-2 locus. Recent studies in our laboratory have demonstrated that T-cell-mediated immune responses are required for overcoming primary Yersinia infection. In the present study, we investigated the course of infection with Y. enterocolitica and the resulting immune responses in Yersinia-susceptible BALB/c and Yersinia-resistant C57BL/6 mice. In the early phase of infection, the clearance of the pathogen was comparable in both strains of mice, suggesting similar mechanisms of innate resistance. Splenic T cells from Yersinia-infected C57BL/6 mice exhibited marked proliferative responses and produced gamma interferon (IFN-gamma) upon exposure to heat-killed yersiniae. By contrast, the Yersinia-specific T-cell response in BALB/c mice was weak, and IFN-gamma production could not be detected before day 21 postinfection. T cells isolated from C57BL/6 mice 7 days after infection mediated immunity to Y. enterocolitica but those from BALB/c mice did not, while at 21 days postinfection T cells from both strains mediated protection. Neutralization of IFN-gamma abrogated resistance to yersiniae in C57BL/6 mice but to a far smaller extent in BALB/c mice. Administration of recombinant IFN-gamma or anti-interleukin-4 antibodies rendered BALB/c mice resistant to yersiniae, whereas this treatment did not significantly affect the course of the infection in C57BL/6 mice. These results indicate that the cellular immune response, in particular the production of IFN-gamma by Yersinia-specific T cells, is associated with resistance of mice to Y. enterocolitica.

Virulence and the immune response in malaria.

Many factors determine the virulence of a malaria infection. These include host innate resistance mechanisms and, with Plasmodium falciparum, the ability to cytoadhere to endothelial cells, form rosettes, and induce release of cytokines. The effect on virulence of acquired immune responses can be determined by Class I and Class II MHC-antigens; levels of immunological responsiveness may be determined too in other ways. The structure of parasite surface antigens and their great diversity modulate the immune response and influence parasite survival and hence virulence, and transmission to the vector.

Role of macrophages in innate and acquired host resistance to experimental scrub typhus infection of inbred mice.

Mechanisms of innate resistance to infection with the Gilliam strain of Rickettsia tsutsugamushi were examined using congenic strains of mice resistant (C3H/RV) or susceptible (C3H/He) to intraperitoneal infection. Both strains of mice were resistant to infection with 1,000 50% mouse lethal doses of rickettsiae if given intravenously. In both systems rickettsial replication occurred after intravenous infection, as evidenced by an increase in rickettsial numbers in the spleens of infected animals, followed by a decrease in rickettsiae to low levels by day 14 postinfection. Administration of the antimacrophage agents silica and carrageenan to C3H/He mice intravenously rendered these animals susceptible to lethal infection. Neither irradiation nor silica given individually rendered C3H/RV mice susceptible to intravenous infection. However, if silica and irradiation were given together, a lethal infection occurred after intravenous infection. C3H/RV mice became susceptible to lethal infection after sublethal doses of irradiation only if they were infected intraperitoneally. Administration of silica or carrageenan had no effect on the outcome of intraperitoneal infection of these mice with Gilliam rickettsiae. These data suggest that both strains of mice share innate resistance mechanisms to intravenous infection that consist of fixed macrophages. Resistance of C3H/RV mice to intraperitoneal infection, in contrast, apparently was dependent only on an irradiation-sensitive process.

Seroepidemiology of H1N1 influenza: striking differences in the attack rate among young people.

The H1N1 influenza outbreak in winter 1977-78 covered the whole of Finland in a uniform fashion, whereas striking differences emerged between various population segments in the susceptible age group. The attack rate was 68 per cent among young servicemen who had been in the armed forces during the epidemic and 33 per cent among those who had entered the service after the epidemic, but only 6 per cent among pregnant women of the same age. Based on routine specimens sent to the laboratory for reasons unrelated to influenza, the attack rate was 4 per cent among children born in 1973-76 and increased by age up to 45 per cent among subjects born in 1957-62. The findings on pregnant women and small children suggest a novel mechanism of innate resistance operating specifically against H1N1 influenza.

Study of the mechanism of innate resistance to virus infection.

Journal of Cellular and Comparative PhysiologyVolume 59, Issue 3 p. 333-373 Article Study of the mechanism of innate resistance to virus infection Gail Theis Goodman, Gail Theis Goodman The Wistar Institute of Anatomy and Biology, Philadelphia, Pa.Search for more papers by this authorHilary Koprowski, Hilary Koprowski The Wistar Institute of Anatomy and Biology, Philadelphia, Pa.Search for more papers by this author Gail Theis Goodman, Gail Theis Goodman The Wistar Institute of Anatomy and Biology, Philadelphia, Pa.Search for more papers by this authorHilary Koprowski, Hilary Koprowski The Wistar Institute of Anatomy and Biology, Philadelphia, Pa.Search for more papers by this author First published: June 1962 https://doi.org/10.1002/jcp.1030590313Citations: 76AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume59, Issue3June 1962Pages 333-373 RelatedInformation