Stress--mechanisms of immunosuppression.

Stress, a term commonly used to describe varied phenomena, should be restricted to describe an adaptive response by an animal to threats to homeostasis. The threats to homeostasis are called stressors. Stressors include a variety of physical, psychological, chemical, or infectious causes that are modified by intrinsic and extrinsic factors. Examples of modifiers include stressor severity, duration, novelty, host genetics and immune status. What may be a stressor to an animal in one situation, when modified, may not be a stressor in another situation. Mechanisms of stress once thought to involve a single pathway described by Seyle as the General Adaptation Syndrome, have been rejected. Four pathways, some incompletely defined, have been implicated in modulation of the immune system. They include autonomic nervous system, the hypothalamic adrenal axis, extra-adrenal pathways involving neuropeptides and neurotransmitters and neuroimmunological mediators. The mechanisms of stress-induced immunosuppression resistance are poorly defined in domestic fowl and will require careful experimentation linking defined stressors with altered physiological responses that affect specific immune function and result in increased disease susceptibility.     

Nutrition--mechanisms of immunosuppression.

Nutritionists must formulate diets that supply adequate amounts of nutrients from five major groups. These are carbohydrate, protein (amino acids), fat, minerals and vitamins. Carbohydrate is usually a cheaper source of energy than fat, but fat is often used to increase the caloric concentration of the diet. Variations in energy intake which may effect immunocompetence usually result from management practices rather than diet formulation. Feed restriction for broiler breeders and withholding feed in forced molting practices may affect immunocompetence. Feed restriction causes higher plasma corticosterone levels, which are known to decrease the immune response, possibly through effects on cytokines. Excessive feed, through forced feeding, may also have short-term effects on indicators of humoral immunity. Protein and amino acid nutrition have been studied in relation to immunocompetence. The level of dietary amino acid needed to maximize growth and feed efficiency will also generally maximize measures of immunocompetence. The level of amino acids needed for maximum growth is lower in chicks which have been immunologically stressed than in chicks which have not. An immune response changes metabolism so that less growth occurs, thereby decreasing the need for amino acids. Dietary levels of minerals can affect immunocompetence. While deficient levels of sodium and chloride decrease humoral immunity, levels of these nutrients which supported maximum growth also supported maximal humoral immunity. Low dietary zinc levels did not affect indicators of immunocompetence in the chick. The effect of fat soluble vitamin levels on the immune system has been studied. Vitamin A is needed to maintain epithelial tissue and prevent infection. Cellular immune response is decreased when the chick is deficient in this nutrient. Several indicators of immune responsiveness are depressed when chicks are vitamin E and/or selenium deficient. Since these nutrients serve as antioxidants, cellular integrity may be affected by a deficiency. Cellular integrity is very important for receiving, and responding to the messages needed to coordinate an immune response. High levels of vitamin E (greater than 10 times the required level) have been found to be immunostimulatory.     

Mycotoxicosis: mechanisms of immunosuppression.

Mycotoxins are structurally diverse secondary metabolites of fungi that grow on feedstuffs consumed by animals and man. The clinical toxicologic syndromes caused by ingestion of fungal toxins have been characterized in domestic animals, poultry and laboratory animals and range from acute mortality to decreased production. Consumption of some mycotoxins, at levels that do not cause overt clinical mycotoxicosis, suppress immune functions and may decrease resistance to infectious disease. The sensitivity of the immune system to mycotoxin-induced immunosuppression arises from the vulnerability of the continually proliferating and differentiating cells that participate in immunemediated activities and regulate the complex communication network between cellular and humoral components. Mycotoxin-induced immunosuppression may be manifested as depressed T or B lymphocyte activity, suppressed immunoglobulin and antibody production, reduced complement or interferon activity, and impaired macrophage-effector cell function. Although the cellular-molecular basis for many of the specific immunosuppressive effects of mycotoxins are presently unclear, inhibition of DNA, RNA and protein synthesis via a variety of different mechanisms appears to be directly or indirectly responsible for the immunosuppressive action of many mycotoxins.     

Evidence of immunosuppression by Demodex canis.

Three clinically normal beagles, 3 beagles with localized demodectic mange (LDM), and 3 beagles with generalized demodectic mange (GDM) were investigated simultaneously 1-3 and 4-6 weeks from the appearance of the clinical signs. Blood clinical examination and reactivity of peripheral lymphocytes to Con A and PHA were investigated in the first instance, and reactivity to Con A, PHA, and LPS in the second. Eight aliquots were used in each blastogenesis assay for each dog. All dogs were negative for rheumatoid factor. The results of blastogenesis showed that many observations were distributed non-normally, and that not all dogs in each group responded homogeneously. Comparison of blastogenesis results between dogs demands careful statistical analysis. Responses to mitogens were normal in all dogs at 1-3 weeks except for the LDM dogs that showed an increased response to PHA. Only the response to Con A was moderately inhibited in the LDM dogs at 4-6 weeks. All responses were severely depressed in the GDM dogs at 4-6 weeks. This means that immunosuppression follows rather than precedes the clinical manifestations of GDM, and implies that the phenomenon is induced by the parasite or the host's reaction to it.     

Virus-induced immunosuppression

Infection with a variety of viruses results in the suppression of the host's immune system. Several mechanisms thought to be responsible for this effect are discussed: infection and alteration of lymphocytes and macrophages, production of soluble suppressor factors, and the induction of suppressor cells. The clinical significance of virus-induced immunosuppression is also discussed.     

Pathology of lymphoid organs with emphasis on immunosuppression.

A review of the literature is presented to include recent diagnostic and research histopathology accessions from poultry produced on the Delmarva peninsula region of the U.S.A. Emphasis is placed on immunosuppression (IS) and pathology of primary lymphoid organs of the chicken. The evolutionary relationship of the avian and mammalian lymphoid systems is based on a common reptilian past with 160 million years of evolutionary dichotomy. Four methods used to assess IS anatomically include: (1) recognition of marked reduction of lymphocytes in both primary and secondary lymphoid organs; (2) recognition of diseases commonly associated with IS; (3) recognition of known immunosuppressive diseases; (4) germinal center enumeration. An experimental method of qualifying and quantifying IS related to single or multiple insults is explored through the use of germinal center enumeration. The effect of stress and inanition on avian lymphocytes must be considered in histological evaluations as chickens are a steroid sensitive species.     

Mechanisms of anticancer drug resistance.

Chemotherapy agents are extremely important in the treatment of liquid malignancies, such as lymphoma, myeloma, and chronic lymphocytic leukemia. In addition, chemotherapy agents have proven effective in the adjuvant treatment of solid tumors, such as osteosarcoma, hemangiosarcoma, transitional cell carcinoma, and others. Unfortunately, chemotherapy resistance in these situations is the most significant cause of treatment failure. Therefore, the ability to predict, treat, or circumvent resistance is extremely likely to improve clinical outcomes. This article has reviewed the most widely investigated forms of chemotherapy resistance, such as reduced drug accumulation, increased DNA damage repair, decreased apoptosis, and others; however, new mechanisms are being found at an alarming pace. In addition, investigations to date have routinely centered on single-cell mechanisms of drug resistance, and cancer is truly a three dimensional disease. The elucidation of mechanisms surrounding (1) how tumors interact with their normal microenvironment, (2) how tumors interact in a three-dimensional environment, and (3) a better understanding of basic tumor physiology and biology may supersede in importance those previously elucidated single-cell mechanisms of chemoresistance.     

Experimental rabies in skunks: effects of immunosuppression induced by cyclophosphamide.

Striped skunks (Mephitis mephitis) were inoculated with street rabies virus and immunosuppressed with several doses of cyclophosphamide. Control skunks were inoculated with street virus only. The skunks were killed in terminal stages of the disease and several tissues were collected for examination by immunofluorescence, light microscopy and viral titration. Sera collected at euthanasia from most of the principals did not contain detectable rabies neutralizing antibodies, whereas high titers occurred terminally in controls. Immunofluorescence was much more entensive in submandibular salivary glands of cyclophosphamide-treated than control skunks. Similarly, virus was isolated from this tissue more consistently and at higher titer from principals than from controls. Immunofluorescence was extensive in brains of all skunks (both groups), but virus was isolated consistently only from brains of cyclophosphamide-treated skunks. Most of the cyclophosphamide-treated skunks had very few inflammatory cells in brain and cerebrospinal ganglia. Neuronal degeneration occurred in dorsal root ganglia of both principals and controls. The results suggest that the immune response has no effect on the development of rabies-induced aggressive behavior, that the immune response may inhibit salivary gland infection and that it is not essential for the development of neuronal degeneration in dorsal root ganglia.     

Evidence for immunosuppression associated with Jembrana disease virus infection of cattle.

Jembrana disease virus (JDV) is a newly recognised bovine lentivirus causing an acute disease syndrome in Bali cattle (Bos javanicus) in Indonesia. We evaluated the effect of JDV infection on the antibody response to chicken ovalbumin (cOVA) and Brucella abortus Strain 19 in Bali cattle. In infected cattle the IgG and IgM response to cOVA was suppressed and delayed and the IgG response to B. abortus Strain 19 was delayed. The results indicate that the humoral immune response is suppressed and delayed in JDV infected cattle.     

Effect of cyclophosphamide immunosuppression on the immunity of turkeys to viral rhinotracheitis.

Turkey poults, free of antibodies to turkey rhinotracheitis (TRT) virus were treated with cyclophosphamide on days 1, 2 and 3 after hatching and vaccinated by eyedrop when 10 days old with a Vero cell-attenuated preparation of TRT virus. No ELISA antibodies to TRT virus developed in the sera of these poults but they were as resistant to virulent virus challenge 21 days later as vaccinated groups which were not cyclophosphamide-treated but produced humoral antibodies. Following challenge with virulent virus at 31 days old cyclophosphamide-treated unvaccinated poults developed a more severe clinical response than untreated birds and had higher virus titres in tracheal swabs. The findings show that the respiratory tract of turkeys may be resistant to TRT despite the absence of ELISA antibodies in the serum.     

Mechanisms of quinolone resistance in Salmonella.

As in other Gram-negative bacteria, mechanisms of resistance to quinolones in Salmonella include target gene mutations, active efflux, and decreased outer membrane permeability. However, the exact contribution of these individual mechanisms to resistance, which may nevertheless interplay to reach high-level resistance, has not yet clearly been defined as in other bacteria such as Escherichia coli. This paper reviews the current state of knowledge of quinolone resistance mechanisms in Salmonella by comparison with that of E. coli and future directions of research with particular attention to the recent development of efflux pump inhibitors as possible means of avoiding the emergence and spread of fluoroquinolone resistance.     

影响家禽免疫的免疫抑制因素

疫苗免疫是控制禽类传染病的主要措施。有的养殖户认为只要按要求进行相应疫病的免疫,就万事大吉。但目前许多养殖户按要求进行了免疫,仍旧发生该类疫病,百思不得其解。本人认为目前免疫失败的主要原因很可能是和各种原因造成的家禽的免疫抑制有关系。     

使肉鸡远离免疫抑制

鸡免疫系统的抑制现象称之为免疫抑制,是由不良的环境条件、落后的管理方式、营养缺乏以及疾病感染所引起的,可导致严重的生产性能下降和经济损失。预防免疫抑制的关键在于采取多种切实有效的措施。     

Osmoregulation in fish. Mechanisms and clinical implications.

Fish have developed remarkable mechanisms for coping with life in water. The salinity/osmolarity of aquatic habitats can be quite variable. Fish have evolved mechanisms for maintaining fluid and electrolyte homeostasis across a wide range of salinities. Marine teleosts, freshwater teleosts, and marine elasmobranchs all utilize different physiologic strategies for osmoregulation. Kidneys do play a role in osmoregulation, but overall, extrarenal mechanisms are equally if not more important sites for maintaining osmotic homeostasis. Extrarenal sites include the gill tissue, the alimentary tract, the rectal gland (elasmobranchs), and the urinary bladder. Through an understanding of osmoregulatory physiology in these three groups of fishes, the effects of injury and disease on fluid and electrolyte balance can be elucidated. Armed with this knowledge and the results of diagnostic testing, safe and effective fluid/electrolyte support can then be instituted.     

Ixodid-host immune interaction. Identification and characterization of relevant antigens and tick-induced host immunosuppression

Ixodid ticks are the most important vectors of pathogens to domestic and wild animals. It is established that cattle and laboratory animal species acquire resistance to tick infestation; acquired resistance has an immunological basis consisting of cell-mediated, antibody-mediated and complement-dependent effector mechanisms. Even though acquired resistance to tick feeding is expressed, host immune competence is possibly impaired during the course of tick feeding. Ixodid-induced transient immunosuppression could possibly facilitate the transmission of vector-borne pathogens and/or enhance tick feeding capabilities in the presence of a host immune response to the hematophagous arthropod. Tick tissue extracts have been used to artificially induce resistance to ixodid feeding, and this has become an area of increasing interest as a possible strategy for tick control. It is essential to have defined antigenic molecules for analysis of host responses to infestation, characterization of immunopathologic processes and for vaccine development. This report focuses on attempts to identify, characterize and isolate tick immunogens. Protein immunoblotting, utilizing sera from animals of different genetic composition and infestation patterns, was used to detect a number of tick polypeptides which are reactive with sera of infested hosts. It is clear that infestation with one ixodid species stimulates antibodies reactive with molecules derived from the sensitizing species and/or tick species in the same genus or different genera. This approach is used to identify molecules that are good candidates for use in immunization studies and for analysis of mechanisms involved in acquisition and expression of resistance to tick feeding.     

Clinical and immunologic aspects of FeLV-induced immunosuppression

Cats exposed to the feline leukemia virus (FeLV) may mount an effective immune response and eliminate the virus, develop a non-viremic, latent infection or become persistently infected and shed the virus. Persistently infected cats commonly die of secondary opportunistic infections that result from FeLV-induced immunosuppression. The acquired immunosuppression is the most frequent and most devastating consequence of FeLV infection in the cat. Immunosuppression is targeted primarily to the cell-mediated immune system and has been attributed to the viral p15e envelope protein. The decreased IgG response and proliferative response to T cell mitogens is thought to be due to a defect in the helper cell function. As a result of T helper cell immunosuppression, infected cats may also have defective cytotoxic lymphocyte and activated macrophage functions which are regulated by their lymphokines. Research has shown that the virus causes a general suppression in the production of T cell-derived lymphokines, including gamma interferon and interleukin 2. A decrease in the function of polymorphonuclear leukocytes has also been reported and may contribute to deaths due to opportunistic infections in FeLV-positive cats. There are numerous parallels between the acquired immunodeficiency syndrome (AIDS) in man and the FeLV-induced immunodeficiency syndrome in cats. Frequent deaths due to opportunistic infections, lymphopenia, depressed cell-mediated immune responses to T cell-dependent antigens despite hypergammaglobulinemia and the presence of a long period of time between infection and the onset of clinical signs are just a few of the syndromes that are similar between the 2 retroviral diseases. A new strain of FeLV, FeLV-FAIDS has been associated with a naturally occurring immunosuppressive syndrome that is strikingly similar to AIDS in man. In addition, a T-lymphotropic retrovirus has recently been identified from cats with an immunodeficiency-like syndrome; this feline lentivirus disease is morphologically similar, but antigenically distinct from the human immunodeficiency virus, the cause of AIDS. Treatment for FeLV immunosuppression is primarily supportive. The development of a soluble tumor cell antigen vaccine has been shown to be efficacious in preventing FeLV infections.