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PubMed1977

Experimental allergic encephalomyelitis: enhancement of cell-mediated transfer by concanavalin A.

Adoptive transfer of experimental allergic encephalomyelitis (EAE) with splenic lymphocytes from Lewis rats sensitized to myelin basic protein (BP) was potentiated by incubation of the cells in vitro with concanavalin A (Con A). Spleen cells of donors which had recovered from EAE also transferred the disease readily after activation by this procedure. In contrast, the transfer of activity of lymph node cells was not altered. We conclude that during the course of EAE a population of T cells with immunologic memory for BP is generated and persists in the spleen. Incubation with Con A activates these cells and results in marked enhancement of their ability to transfer the disease.

Animals↗
PubMed1988

[Non-specific immune defenses present in pregnancy].

The state of pregnancy changes the immune system by allowing the trophoblast to go on developing without letting the mother's body be invaded by it, and by keeping intact immune defences against the usual assaults. The non specific immune system is the first bulwark against invaders. The elements of this system, which do not depend on immunological memory, are: the macrophage-monocyte system, Natural Killer cells (NK), the complement component and other bactericidal substances such as lysozyme, fibronectin and interferon. Pregnancy improves the working of the monocyte-macrophage system. In fact, the macrophages of th reticulo-endothelial system, which can be found in different strategic places in the body, phagocytose abnormal particles more intensely. The monocytes in the circulation are more aggressive in pregnancy. They are drawn to the feto-placental interface where they are activated by different lymphokines and cytokines which can be found in quantity at this site. The role of these local active monocytes is not limited only to phagocytosis because among the hundred substances that they can elaborate are some that will regulate trophoblastic proliferation. The activity of the Natural Killer cells that are circulating and which can control tumour cell growth and cells infected by viruses is lowered in pregnancy. The serum taken from pregnant women seems to have a substance that counters the maturation of the Natural Killer cell lines. The complement system of protein synthesis, which normally acts to lyse bacteria in the chemotaxis during opsonisation, is raised in pregnancy. At the feto-placental interface it does seem to activate this system but not elsewhere in the general circulation. Interferon, which is a molecule that normally activates NK cells, has been found at the feto-placental site, without seeming to have a particular role. Pregnancy changes the quantity and the distribution of other elements in the non specific immune system such as transferrin , fibronectin and beta-lysin.

Female↗
PubMed1987

The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis.

Mice infected i.v. with the virulent Erdman strain of Mycobacterium tuberculosis exhibited three distinct phases of infection within the spleen. These consisted of a primary phase, characterized by the progressive growth of the organism; a secondary phase, in which the viable organism was progressively eliminated; and a tertiary phase, characterized by a chronic or slowly recrudescing disease state. Passive transfer experiments, in which T cell-enriched spleen cells from immune donors were infused into T cell-deficient recipients and were measured for their capacity to adoptively protect these mice from challenge with M. tuberculosis, provided evidence that at least three separate populations of protective T cells were acquired in response to the infection within the time frame of the experiments. These populations of T cells could be distinguished in that they differed in their expression of the L3T4 and Lyt-2 cell surface molecules, in terms of their kinetic profiles of emergence and loss, and (c) in terms of their susceptibility to cyclophosphamide. The results may suggest that different populations of protective T cells can be generated at different times during the infection as various classes of antigens (for example, metabolic or structural antigens) become available for presentation by host macrophages. It is hypothesized, furthermore, that the kinetics of emergence and loss of these various populations may reflect switching in the mode of immunity being expressed, particularly during the chronic phase of the infection, from that of a state of active immunity to one of immunologic memory.

Animals↗
PubMed1988

Prospects for HIV vaccines.

This article initially discusses the types of responses elicited by infectious agents, such as viruses and the role of each response in preventing, limiting, and clearing the infection. An important response is the generation of immunological memory, in both the B and T cell compartments. Generally, attenuated viral vaccines have been highly successful at inducing long-lived immunity but our understanding of the reasons for this comes from the study of model systems, such as murine influenza virus infections. Specific antibody may largely prevent infection and specific cytotoxic T cells and antibody-dependent cell cytotoxic reactions are the main mechanisms for clearing viral infections. Recent evidence shows that for some months after infection by HIV, a strong cytotoxic T (Tc) cell response occurs in infected, asymptomatic individuals; these cells are continuously generated by HIV-infected stimulator cells that most likely also serve as target cells in vivo. A low level of specific antibody is also formed and a number of reasons are listed to explain why HIV escapes antibody-mediated neutralization and infects cells expressing CD4 receptors. Cells of the macrophage/monocyte lineage are also infected and these express Fc and complement receptors; there is the strong possibility that infection of these cells occurred following the formation of complexes of infectious HIV with antibody to the surface antigen and attachment of complement components. The continuous presence of activated Tc cells that, in contrast to many other viral diseases, does not clear the infection strongly suggests that foci of infected cells sequestered from or resistant to immune control become established. These secrete virus that infects other (stimulator) cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1977

The appearance of non-specific antibody-forming cells in the efferent lymph draining antigen-stimulated single lymph nodes.

Immunization of single lymph nodes with various antigens led to the appearance of cells in the efferent lymph that secreted antibody specific for the antigen which induced their formation and for a number of unrelated, non-crossreacting antigens. Immunization of single lymph nodes with mitogens led to the appearance of cells secreting antibodies specific for an even greater number of antigens, including one (TNP) that in all probability is not present in the animals' natural environment. When the node was primed with one antigen, a subsequent challenge with an unrelated antigen 12 weeks later led to the appearance of greater numbers of cells containing and secreting antibody against the previously experienced antigen, than was the case in unprimed lymph nodes. These findings indicate that the immune response to antigen provokes the maturation of lymphocytes of specificities unrelated to that of the injected immunogen. Such a mechanism may be important in maintaining immunological memory. Mitogens may directly activate lymphocytes into maturation and expression as antibody-secreting cells, whereas antigens appear to act indirectly.

Animals↗
PubMed1986

Epidemiological study of swine influenza virus as a component of the respiratory disease complex of feeder calves.

A survey of 177 paired calf sera collected during the years 1978-1981 showed that 3.4% of the calves had prior experience with swine influenza virus. Six calves positive by the single radial hemolysis test (SRH) were also positive by the virus neutralization test (VN) in chicken embryos, and one calf reacted with all three tests (hemagglutination-inhibition (HI), SRH, and VN). The SRH and HI tests available cannot adequately provide the information necessary in a survey of this sort. The HI test is subject to too many variations to enable the data to be used with any degree of confidence. The SRH test lacks accepted standarization for performing the test with cattle sera. Therefore, the VN test is necessary for confirmatory results.

Animals↗
PubMed1986

[Detection of immunosuppression factors in Shigella sonnei].

A factor, making noninvasive shigellae and other bacteria capable of suppressing immunological memory and secondary immune response manifested as delayed hypersensitivity, has been detected in the germ-free filtrates of the broth cultures of invasive S. sonnei.

Animals↗
PubMed1985

Lymphokine-activated tumor inhibition in vivo. I. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth.

CE-2 is a chemically induced tumor of low immunogenicity in syngeneic BALB/c mice. Nylon wool columns eluting lymphocytes from the spleen of mice bearing clinically evident (5-mm mean diameter) CE-2 tumors (CE-2 TB lymphocytes) do not react with CE-2 cells in vitro, nor are they able to affect their growth in vivo in a Winn-type neutralization assay at 5:1 lymphocyte:tumor cell ratio. However, they become able to inhibit CE-2 tumor growth when 20 U of interleukin 2 (IL 2) in 0.4 ml are injected daily for 10 days at the challenge site. In contrast, mice injected with CE-2 cells and IL 2 only display tumor takes and growth that are not significantly different from those in controls challenged with CE-2 cells alone. This lymphokine-activated tumor inhibition (LATI) is not a peculiarity of the CE-2 tumor-host combination, because different tumors can be inhibited in this way and various TB lymphocytes can initiate it. In these experiments, IL 2-rich 25,000 to 30,000 m.w. fractions were obtained routinely from the culture supernatants of a clone of EL-4 thymoma stimulated with phorbol myristic acetate. Equally active IL 2-rich preparations were obtained from rat spleen cells stimulated with concanavalin A, or from MLA 144 gibbon lymphosarcoma spontaneously releasing IL 2. Treatment of CE-2 TB lymphocytes with various antibody and C, with 2000 rad gamma-irradiation, or fractionation on Percoll density gradients suggested that radioresistant functions of Thy-1.2+, Lyt-1.2+, Lyt-2.2- and of asialo GM1+ cells are independently involved in LATI induction. These lymphocytes inhibit tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor destruction. CE-2 tumor inhibition by LATI leaves a specific delayed-type hypersensitivity and an immunologic memory, resulting in rejection of a second lethal CE-2 challenge in a significant number of mice.

Adenocarcinoma↗
PubMed1985

[High-molecular antigenic complex of the pneumococcus: its properties].

The study of an antigenic preparation isolated from pneumococci, serotype 3, by the method of alkaline hydrolysis has revealed that the preparation contains a high-molecular complex protein-polysaccharide composition of the cell wall of this microorganism. The preparation contains at least two immunologically active components: the type-specific polysaccharide of serotype 3 pneumococcus and a nonspecific protein component. This antigenic preparation is capable of the formation of immunological memory in mice and protecting them from experimental challenge with pneumococci of homologous and heterologous serotypes.

Animals↗
PubMed1975

Immunity to influenza.

Immunity to influenza virus may be considered from the standpoints of viral and hostfactors. Amonst viral factors the phenomena of antigenic 'shift' and 'drift' of the surface antigens. Hemagglutinin HA and neuraminidase NA, are of utmost importance in enabling the virus to combat host immunity and to produce recurrent pandemics and epidemics of disease. 'Shift' involves major changes in the antigenic character of the HA and NA antigens, and serological studies reveal little or no crossreactions between antigens of different subtypes. However, immunological 'memory' may exist between the surface antigens of viruses of different subtypes, for example between the hemagglutinins of Asian (H2) and Hong Kong (H3) subtypes. Antigenic 'drift' occurs more frequently than 'shift' and involves subtle changes in the antigenic configuration of HA and NA within a subtype. It is clear that the hemagglutinin antigen contains a multiplicity of antigenic determinants, one or more of which remain stable (CR determinants) whilst others (strain-specific determinants) change completely during antigenic 'drift'. Amongst host factors humoral antibody to HA and NA appears to be a reasonable index of natural or vaccine induced immunity to infection. As far as the specificity of such antibodies is concerned, it is likely that future studies will place considerable emphasis on the distinction between antibody for the stable (CR) antigenic determinants and antibody to strain-specific determinants. It seems likely that antibody to strain-specific determinants is of more relevance to immunity than CR antibody. The studies of Virelizier et al. described elsewhere in this Symposium employing single-radial-diffusion tests give hope of simple methods for the investigation of such antibody specificity. There is no evidence that antibody to the internal, antigenically stable ribonucleoprotein is related to immunitywhilst the role of the other internal antigen, the membrane protein, in immunity is at present unknown. Numerous studies have been carried out to establish the importance of secretory antibody in the respiratory tract. Although secretory IgA specific for the influenza virus has been clearly demonstrated in the respiratory tract, the levels are low and its significance is not yet established. Whilst the role of cellular aspects of immunity to influenza in man remains to be established there is no doubt from the recent studies of Tyrrell and his colleagues that delayed hypersensitivity to influenza antigens can be demonstrated. In considering the host aspects of immunity it is important to attempt to distinguish factors which are merely an index of past exposure and those which are involved with the actual mechanism of immunity. It is likely that animal experimental models, in particular with inbred mice, will provide an important contribution in this field of investigation.

Antibodies, Viral↗
PubMed1983

Use of spleen organ cultures in the analysis of hemopoietic alterations induced by irradiation and allogeneic marrow transplantation.

The transplantation of 0.5-1 X 10(7) BALB/c mouse bone marrow cells into lethally irradiated CBA recipient mice and the subsequent explantation of the recipient spleens resulted in active hemopoietic progenitor cell (colony forming cell; CFC) regeneration in organ cultures but not in vivo. In order to establish what hemopoietic elements essential for CFC regeneration are altered in vivo as a consequence of allogeneic donor/recipient interactions, the ability of spleens to support CFC regeneration in organ cultures was analysed when these were removed from irradiated recipients at various time intervals after allogeneic marrow transplantation. It was found that an inhibition of differentiation of hemopoietic stem cells (CFUs) and committed hemopoietic progenitor cells (CFC) occurred initially in allogeneic marrow graft recipients followed by an alteration of growth supportive spleen stromal elements. The latter appears to consist of at least two distinct components: a nonspecific component and a specific component with the features of immunologic memory.

Animals↗
PubMed1983

Fine specificity of the in vitro antibody response to influenza virus by human blood lymphocytes.

The fine specificity of anti-influenza antibody produced in vitro by human PBM stimulated with different strains of influenza virus was examined by competition binding in solid phase enzyme immunoassay. Most of the antibody produced in vitro is directed to strain-specific or cross-reactive determinants on the hemagglutinin molecule. The extent of cross-reactivity is dependent on the strain of virus used to stimulate PBM as well as the individual tested and presumably on his previous exposure to influenza viruses. PBM from some individuals produced antibody that bound to the stimulating strain of influenza virus but not to other strains of the same subtype. In other individuals, antibody was produced in vitro that cross-reacted with all viruses in the same subtype (e.g., H3N2; A/X31, A/X47, and A/Texas) but did not bind to other (H2N1 or H1N1) subtypes, and in a few individuals, extensive cross-reaction between subtypes was seen. The presence of antibody to hemagglutinin in these culture supernatants was confirmed by competition binding to highly purified hemagglutinin. This in vitro culture system allows the immunologic memory of individuals to a wide range of stimulating virus strains to be examined simultaneously in terms of specificity of the antibody response by human PBM to influenza virus after natural infection or immunization.

Adult↗
PubMed1983

The effects of oral and combined parenteral/oral immunization against an experimental Escherichia coli urinary tract infection in mice.

A double oral immunization (PO/PO) with an outer membrane protein (OMP) from a human uropathogenic strain of Escherichia coli, resulted in the partial protection of mice infected per urethrally with the same strain. Complete protection was achieved by immunizing with OMP in Freund's complete adjuvant (FCA), intramuscularly (i.m.), followed by an oral boost (i.m./PO). The PO/PO protocol stimulated mainly local urinary antibody synthesis, particularly IgA, whilst the i.m./PO regimen resulted in the appearance of both serum and urine antibodies. A single dose of OMP, 6 days after infection, rendered the mice resistant to reinfection, in contrast to non-immunized mice, and led to a significant increase in urine, serum and bile IgA anti-OMP levels. Our results confirm previous reports that the urinary tract forms part of the common mucosal immune system and provides further evidence for immunological memory in mucosal immunity. These results also demonstrate that our OMP preparation is a highly effective immunizing antigen, and that such preparations may be suitable as oral vaccines against urinary tract infection in humans.

Administration, Oral↗