The basis for immunity, natural or acquired. Natural immunity osteopathically developed or safeguarded. 1938.
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Natural immune reactions are mediated by lymphocytes, macrophages/monocytes, and neutrophils. The latter have been implicated in a variety of self-surveillance models, i.e., activity against malignant host cells, participation in wound repair, and infliction of damage in postischemic perfusion injury. Better characterized are the interactions with unopsonized pathogens through lectinophagocytosis mechanisms, where the lectin resides either on the phagocyte or on the microorganism. This review examines the infection by influenza A virus (IAV) of the human neutrophil, which results in the vigorous metabolic response of the cell to generate toxic oxygen species. This response is not necessarily characteristic of response to unopsonized particles, as the neutrophil exhibits no such activity to unopsonized zymosan or chlamydia. The virus elicits calcium mobilization from intracellular stores through a pertussis toxin-insensitive mechanism, and in its particulars the activation cascade is unique in comparison to any other characterized agonist. The putative receptor for the IAV binding protein, hemagglutinin (HA), contains the sialic acid residues; identification of specifically linked protein receptors will allow characterization of this stimulation pathway and will define the molecular biology of this activation sequence. Insight into this particular pathway may allow definition of a primitive recognition system that represents a fundamental basis for discernment of self and nonself entities.
Comments were made on misinterpretations concerning the natural resistance and natural immunization against tetanus. Arguments were given explaining why the disease itself did not determine adequate immunity. When, however, adequate conditions appear, tetanus toxin is known to stimulate the immune system and produce detectable humoral antibodies. Various possibilities resulting from the postulated harboring of tetanus bacilli by the human body and their eventual toxin production were analyzed and related to the human tetanus pathology. The existence of natural immunization was unquestionably demonstrated by presence of protective levels of tetanus antitoxin in the blood of the majority of 59 surveyed subjects considering that none of them had ever received any tetanus toxoid and most of them never received a single shot of any drug. The results of this survey originated a few arguments that may support the answer to some still intriguing phenomenona such as: 1. The relatively small number of cases of overt disease among people and animals born and living in large tetanus-risk regions all over the world. 2. The existence of "poor responders" and "good responders" to the primary tetanus toxoid stimulus. 3. The age distribution of tetanus showing evident prevalence among newborns and children. 4. The wide individual variations in the clinical picture of human tetanus as indicated by the localization and limitation of the symptoms and their severity.
Invertebrate immunity exhibits immediate recognition without prior contact. Here, Tom Humphreys and Ellis Reinherz propose that receptors capable of actively recognizing self histocompatibility antigens could be generated by a process similar to positive selection, and that these could guide 'natural immunity' to foreign cells. These ideas provide a conceptual basis for invertebrate immunity and for understanding the evolutionary precedents for T-cell-mediated antigen recognition.
Natural antibody has been proposed as a mediator of T-independent (natural) resistance to tumors and microbial pathogens. In this article, it is argued that the "priming" of the B cell repertoire by ubiquitous microorganisms and autoantigens results in natural antibody production and this response offers a survival advantage for the host as a consequence of the participation of these antibodies in natural resistance.
Secretory immunity. 1. Intense endurance exercise suppresses salivary immunoglobulins. The exercise-induced decrease is specific for the secretory antibodies IgA and IgM. 2. The suppression of secretory Ig is transitory, lasting at least one hour, and returning to pre-exercise levels by 24 hours after a single bout of severe exercise. These results suggest that anecdotal statements by athletes and their coaches of an increased susceptibility to upper respiratory infection after severe exercise could be related to changes in secretory immunity. Natural immunity. 1. Natural killer activity of PBL is suppressed one hour after intense endurance exercise. This effect is transitory, since activity returns to pre-exercise levels by 24 hours after a single bout of exercise. 2. The decrease in NK lytic activity is due to a decrease in the percentage of NK cells (Leu-11a+ cells). When NK cell activity is expressed on a per cell basis, it appears that activity is enhanced after exercise.
The anti-fungal azole drug itraconazole was compared with fluconazole regarding immunosuppressive effects in a model of human alloreactivity in vitro (the mixed lymphocyte culture, MLC) and in assays of non-adaptive immunity (natural killing, NK, and lymphokine activated killing, LAK). Itraconazole, but not fluconazole, strongly inhibited lymphocyte proliferation and the generation of allospecific cytolytic activity, but had no effect on the development of major histocompatibility complex (MHC)-unrestricted ("natural killer-like") cytotoxicity or of alloindifferent suppressive activity in MLC. Neither drug blocked LAK cell induction, nor the effector phase of either NK or LAK activity. These results suggest that itraconazole might represent a new class of immunosuppressive agent which specifically blocks alloreactivity without affecting natural immunity.
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Consideration of cell-mediated cytotoxicity as an enzyme-substrate reaction provided a theoretical and practical basis for the quantification of natural immunity to solid tumours. The natural cytotoxic activity of spleen cells from normal rats towards cultured target cells from solid tumours, measured in a 6 h chromium release assay, developed between 2 and 5 weeks after birth and, in contrast to previous reports of natural cytotoxicity against lymphoid tumour cells, showed no sign of decline up till at least 22 months of age. Both virgin and breeder (multiparous) females showed equally good maintenance of natural immunity, and the apparent specificity of this natural immunity on a panel of four target cells did not change between 8 weeks and 18 months of age. The low level of natural immunity in infant spleen, and also in adult lymph nodes and thymus, was not caused by suppressor cells but rather by an absence of appropriate effector cells.
The virus-host relationship in BALB/cfC3H virgin female mice neonatally infected with an oncogenic virus (mammary tumor virus) (MuMTV) was significantly altered by a brief immunosuppressive treatment during young adult life. Natural immune responses were augmented and changed. The ability of lymphoid cells to attack target cells expressing MuMTV-associated antigens was significantly increased, and a new component, a non-T-cell reactivity, was added to the T-cell reactivity found in normal females. Serum blocking factors were both quantitatively and qualitatively altered.
Tick saliva has been shown to contain a variety of pharmacologically active molecules, including those with immunosuppressive activities. There is increasing evidence that the nonspecific suppression of host immunity by tick saliva is exploited by tick-borne pathogens, e.g. the saliva-activated transmission (SAT) of some tick-borne viruses. We have demonstrated the suppressive effect of the salivary gland extract (SGE) derived from partially fed (five days) Ixodes ricinus females on important mechanisms of innate immunity: natural killer (NK) cells, interferon and nitric oxide production. SGE reduced the interferon induction by polyinosinic-polycytidylic acid (poly I:C) or Escherichia coli lipopolysaccharide (LPS) in a culture of Balb/c mouse splenocytes by 94% and 62%, respectively. SGE suppressed the cytotoxicity of nonstimulated and in vivo poly I:C-stimulated mouse NK cells by up to 31% and 26%, respectively. The induction of NK activity in vitro by LPS but not by Concanavalin-A (Con-A) was also downregulated in the presence of SGE. The addition of SGE to cultures of mouse macrophages partially inhibited the production of nitric oxide, induced by LPS. These data suggest that the facilitating effect of SGE on the transmission of some tick-borne pathogens might be associated with the suppression of the host innate resistance mechanisms, represented by interferon, nitric oxide and NK cells.
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A natural response acting to discriminate between allogeneic and syngeneic lymphocytes in vivo is described for normal mice. Eighteen to 24 h after systemic injections of low doses of 51Cr-labeled cells, less radioactivity is found in the lymph nodes after allogeneic transfer. The spleen but not the liver participates in the response. It can be abolished by neonatal induction of transplantation tolerance, is shown to be immunologically specific, and is resistant to irradiation up to 1000 rd, although a radiosensitive phase occurs during recovery from sublethal irradiation. The response is cell-mediated but depends upon cooperation from a factor present in normal serum. It is thymus-independent: this clearly distinguishes it from the superficially similar immune response acquired by immunization and aligns it with the class of responses to which the hybrid histocompatibility response and natural killer-like phenomena belong. Unlike these, however, it is present at birth and directed primarily against H-2 antigens. It appears to follow the classical transplantation rules in a limited range of strains. Some of the difficulties inherent in this type of study are discussed.
We have examined the ability of in vivo treatment of mice with recombinant interleukin 2 (rIL-2) to affect natural immunity measured against tumor (YAC-1) or virally infected (herpes simplex type 1) target cells. rIL-2 treatment leads to significant increases in natural killer/lymphocyte-activated killer (NK/LAK) function and spleen cells recovered. This effect is dose dependent and strain related. The latter parameter correlated with the pretreatment NK activity level of the strain. The rIL-2 induced NK/LAK augmentation is also kinetically restricted as treatment must have occurred within 48-72 h of assay to be effective. The rIL-2 therapy effectively enhances both antitumor and antiviral NK/LAK activity and results in a noticeable increase in asialo-GM1-positive cells in the spleens of treated mice as well as a significant increase in IL-2 receptor expression as monitored by either cytometry or radioligand binding. In vivo treatment of mice with an antibody directed to the ASGM1 determinant effectively reduces the rIL-2 augmentation of both antitumor and antiviral activity even though this treatment does not affect the pretreatment level of antiviral activity. Various natural and induced immunodeficiency states (immunotherapy, irradiation, immunosuppressive drugs, cytoreductive drugs) have been examined for the ability of in vivo treatment with rIL-2 to enhance NK/LAK activity. In vivo rIL-2 administration is differentially effective in enhancing NK/LAK activity in these situations. Notably, in these induced immunodeficiency states, although NK/LAK activity is commonly enhanced, the number of spleen cells recovered often is only marginally affected. Thus, as expected, a limiting aspect in this use of a natural immunomodulator is the number of potentially responsive cells present in the immunodeficiency condition. In addition, correlations between rIL-2 effect, several of the immunodeficiency states, and vascular leak syndrome are briefly discussed.
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A heritable alteration in the natural immunity as measured by changes in the natural killer (NK) cell activities of peripheral blood lymphoid-cells was found to occur in rats upon an in utero exposure to iodine-131. The model that was employed for the measurements consisted of Fischer F344 inbred rats exposed to iodine-131 (sodium) during their 16th to 18th day of gestation. The natural immunity of the animals was evaluated by determining the NK cell activities of peripheral blood lymphoid cells of the offsprings when they reached 2 months of age. Immediately following determination of the natural immunity, brother and sister matings were carried out for evolution of the families. Study of these pedigrees revealed an impairment in the natural immunity to persist through two generations (F1, and F2) of the male animals. The hematological profiles of the animals suggest that the insult may alter the numbers of red and white blood cells in the succeeding generations, but has little noticeable effect upon the percentage of lymphocytes. The interpretation of the results indicate that a perinatal insult by iodine-131 during late gestation can result in both somatic and germ cell changes in the immunological system. Thus, there appears to be a genealogical memory to an in utero radionuclide insult which may adversely affect the offspring's immunological competency to respond to subsequent insults.