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PubMedDate not supplied

Substance P increases and prolongs increased output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo: is it a mediator of immunological memory?

There are receptors on lymphocytes for substance P which are found both on small recirculating and on blast lymphocytes. The principal effect of substance P on lymphocytes appears to be a stimulating one, both in vitro and in vivo. The in vivo administration of substance P to sheep by acute infusion into cannulated afferent lymphatics of peripheral lymph nodes has been found to stimulate efferent lymph flow and the output into efferent lymph of both small recirculating and blast lymphocytes. We here report that substance P both enhances and prolongs the enhancement of the output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo. This output-stimulating effect appears to be specific to T4 (CD4) lymphocytes and is associated with a depressant effect on the output of T8 (CD8) and B lymphocytes. The output-stimulating effect on small T4 (CD4) lymphocytes is quite prolonged, lasting in excess of 96 h after a single 50 micrograms acute infusion. A brief post-infusion depression in T4 (CD4) lymphocyte output is associated with an equally brief, but marked, elevation in the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. The output-stimulating effect of substance P on blast T lymphocytes is confined to the T4 (CD4) blast lymphocytes. Substance P or a similar molecule may be of value when a specific T4 (CD4) lymphocyte output stimulant effect is desired. A single prior (6 days) acute infusion of substance P into a popliteal lymph node via its cannulated afferent lymphatic produced profound changes in the response to nodal drainage area immunization with killed S. muenchen bacteria. The latent period prior to increased antibody production was abolished, as was the standard post-immunization 'shutdown' period of decreased output of lymphocytes into efferent lymph. These changes were accompanied by a marked and progressive increase in antibody production. The findings reported here suggest substance P-induced long-term potentiation (LTP) of the immune response and raise the question of an involvement of substance P as a major mediator of immunological memory.

Animals↗
PubMed2004

Immunisation schedules for non-replicating nasal vaccines can be made simple by allowing time for development of immunological memory.

Mice immunised intranasally with multiple doses of outer membrane vesicles (OMVs) from group B meningococci developed antibody responses that depended on the interval between doses. High levels of antibodies in saliva and extracts of faeces were induced within 4 weeks after an OMV vaccine had been given at weekly intervals, whereas the antibody responses in these samples were negligible when given four times at 1-day or 1-h intervals, or as one large dose. Only modest responses were obtained in serum after 4 weeks, however, whether the vaccine had been given repeatedly at any schedule, including the 1-week interval, or as one dose. On the other hand, two large doses given 8 weeks apart induced booster antibody responses in both serum and secretions that matched the responses from a second series of the four smaller doses. Intranasal immunisations may thus stimulate immunological memory more rapidly in secretions than in serum. In order to secure adequate systemic responses by a minimum of doses, nasal vaccines should therefore be given at intervals longer than 4 weeks, in harmony with the intervals recommended for injectable vaccines.

Administration, Intranasal↗
PubMed1993

The relation between T-cell expression of LFA-1 and immunological memory.

Antibodies against isotypes of the leucocyte common antigen (LCA, CD45) can be used to identify largely reciprocal subsets of human peripheral T cells, characterized by differential ability to respond to recall antigen in vitro. The transition from naive, unprimed T cells to memory cells capable of responding to recall stimulating has been associated with a switch in surface expression of CD45 from the CD45RA isotype to CD45RO. It has been proposed that this transition is accompanied by the coordinated up-regulation of a number of cell-surface molecules involved in cellular adhesion and/or activation, including the leucocyte function-associated antigens (LFA). In the present study we have examined the expression of LFA-1 on subsets of human peripheral T cells, and related it to the expression of markers of cellular activation and CD45 isotypes, and thus to immunological memory. Our results suggest that the intensity of LFA-1 expression on the surface membrane of human peripheral T cells is not tightly associated with maturation status as judged by LCA isotype expression, but rather reflects the degree of cellular activation. This conclusion is supported by data of T-cell function in vitro, showing similar antigen- and mitogen-induced proliferative responses in T-cell subsets characterized by low as well as high surface expression of LFA-1.

Adult↗
PubMed1997

Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide-protein conjugate vaccine.

Two hundred twenty-one Gambian children vaccinated previously with one, two, or three doses of a meningococcal conjugate vaccine or two doses of polysaccharide vaccine before the age of 6 months were revaccinated at the age of 18-24 months with either meningococcal polysaccharide, conjugate, or inactivated polio vaccines. Children who had previously received one, two, or three doses of conjugate vaccine had significantly (P < .001) higher anti-group C meningococcal antibody levels following revaccination than did children vaccinated with a polysaccharide vaccine for the first time. Children vaccinated previously with two doses of polysaccharide vaccine had a lower group C antibody response than did control children. Group A antibody responses following revaccination of children who had previously received polysaccharide or conjugate vaccine were not significantly higher than those in control children. Thus, immunologic memory was probably induced by the group C but not by the group A component of the conjugate vaccine.

Antibodies, Bacterial↗
PubMed1981

Immunologic consequences of antibiotic-induced abridgement of bacterial infection: effect on generation and loss of protective T cells and level of immunologic memory.

Ampicillin was employed in mice to determine the effect of rapidly abridging bacterial infection on the generation of T cell-mediated antibacterial immunity. It was found that antibiotic-induced abridgement of infection with Listeria monocytogenes had a pronounced effect on the generation of splenic T cells capable of adoptively immunizing normal recipients against a Listeria challenge infection. Ampicillin given at the time of maximum bacterial growth at 24 hr caused a striking reduction in the number of protective T cells produced at the time of peak response on day 6. Although the greatest effect was caused by giving ampicillin early in infection, a significant reduction in peak T cell production occurred even when Ampicillin was given as late as day 5. On the other hand, the effect of abridging infection at the onset of decay of the anti-Listeria response was to cause protective T cells to be lost from the spleen at a much faster rate. These results clearly show that regardless of any immunoregulatory mechanism involved, the duration of generation, and the onset and duration of decay of the anti-Listeria response are determined by the number of replicating Listeria in the tissues. Moreover, Ampicillin-induced abridgement of infection, either before or at the time of peak primary response, resulted in the expression of greatly reduced levels of immunologic memory at a later time. This indicates that memory cells are generated throughout the entire course of the primary anti-Listeria response, including the period of its decay.

Ampicillin↗
PubMed1991

Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory.

We have examined secretory antibody and cell-mediated immune responses to oral cholera vaccine in the human gastrointestinal mucosa. Freshly isolated peripheral blood lymphocytes and intestinal lymphocytes obtained by enzymatic dispersion of duodenal biopsies were assayed for numbers of total and vaccine specific immunoglobulin-secreting cells by enzyme-linked immunospot assay (ELISPOT) techniques; the frequency of cells secreting interferon-gamma (IFN-gamma) was also examined by a new modification of the ELISPOT technique. After booster immunizations with oral cholera vaccine, large numbers of cholera toxin-specific antibody-secreting cells (ASC) appeared in the small intestine. The responses were dominated by IgA ASC. A single immunization, performed 5 mo after the initial vaccinations, gave rise to an ASC response similar to that seen after the first booster immunization, with respect to both magnitude and isotype distribution. Each of the immunizations also evoked an ASC response in blood which was of lower magnitude than that seen in the small intestine, and comprised similar proportions of IgA and IgG ASC. A booster immunization also resulted in increased frequencies of IFN-gamma-secreting cells, but this increase was confined to the duodenal mucosa. This study establishes the feasibility of studying, at the single-cell level, intestinal immune reactivity in humans. Furthermore, it indicates that the small intestinal mucosa is an enriched source of IFN-gamma. It also demonstrates marked differences between intestinal and peripheral blood immune responses after enteric immunization, and confirms the notion that the mucosal immune system in humans displays immunological memory.

Administration, Oral↗
PubMed2001

Persistence of immunologic memory in long-term hemodialysis patients and healthcare workers given hepatitis B vaccine: role of a booster dose on antibody response.

Hepatitis B (HB) vaccine is effective in producing protection against HB virus infection, but the persistence of immunity remains largely unknown. Seventy-six hemodialysis (HD) patients (60 after primary HB vaccination and 16 with natural immunity) and 46 healthcare workers (32 after primary HB vaccination and 14 with natural immunity) were followed up for 10 years to evaluate the persistence of immunity. Ten years after vaccination, the analysis showed a lower seroconversion rate (38 vs. 75%, p < 0.001) in HD patients as compared with healthcare workers. In the follow-up period, the protective immunity developed through HB virus infection also showed a lower seroconversion rate (44 vs. 86%, p < 0.025) in HD patients as compared with healthcare workers. To assess the status of immunologic memory, we administered a booster dose of HB vaccine 3-12 years (mean 6.7 +/- 0.6 years) after primary vaccination in a selected group of 37 HD patients who presented a decline of their antibodies or were nonresponders. In another group of 12 healthcare workers who had a decline of their antibodies, we also administered a booster dose of HB vaccine 5-8 years (mean 5.8 +/- 0.3 years) after primary vaccination. Nineteen of the 37 HD patients (51%) presented an anamnestic response to the booster dose, and 15 of these (40%) were high responders. All of the healthcare workers responded to the booster dose with a high antibody response. We conclude that patients undergoing HD not only have lower rates of immunization to HB than healthy adults, but also that these are frequently transient. Booster doses after a primary course of vaccine are effective in about the half of HD patients who presented a decline of their antibodies or were nonresponders but whether they are necessary is unclear. The majority of healthcare workers continue to have high levels of protective HBs antibody for at least 10 years and routine boosters are not required.

Female↗
PubMed2001

Meningococcal outer membrane vesicle vaccine given intranasally can induce immunological memory and booster responses without evidence of tolerance.

We have studied the ability of outer membrane vesicle (OMV) vaccines from Neisseria meningitidis serogroup B to induce vaccine-specific antibody and spleen cell proliferative responses in mice after being administered intranasally (i.n.) and/or subcutaneously (s.c.). A series of four weekly i.n. doses (25 microg) without adjuvant or a single s.c. dose (2.5 microg) with aluminum hydroxide was followed 2 months later by secondary i.n. or s.c. immunizations. After i.n. priming, both immunoglobulin G (IgG) antibody responses in serum, measured by enzyme-linked immunosorbent assay, and IgA antibodies in saliva and extracts of feces were significantly boosted by later i.n. immunizations. The IgG antibody responses in serum were also significantly augmented by secondary s.c. immunization after i.n. as well as s.c. priming. Sera from mice immunized i.n. reached the same level of bactericidal activity as after s.c. immunizations. The s.c. immunizations alone, however, had no effect on mucosal IgA antibody responses, but could prime for booster antibody responses in secretions to later i.n. immunizations. The i.n. immunizations also led to marked OMV-specific spleen cell proliferation in vitro. Both serum antibody responses and spleen cell proliferation were higher after i.n. priming and later s.c. immunizations than after s.c. immunizations alone. There was thus no evidence that i.n. priming had induced immunological tolerance within the B- or T-cell system. Our results indicate that a nonproliferating meningococcal OMV vaccine given i.n. can induce immunological memory and that it may be favorably combined with similar vaccines for injections.

Administration, Intranasal↗
PubMed2000

Long-term immunological memory in the resistance of rats to transplanted intracerebral 9L gliosarcoma (9LGS) following subcutaneous immunization with 9LGS cells.

Glioblastoma multiforme (GBM) is the most common primary human brain tumor. About 7000 new cases are diagnosed yearly in the USA. Despite current neurosurgical and postoperative radiotherapeutic tumor cytoreduction methods, in most cases occult foci of tumor cells infiltrate surrounding edematous brain tissues and cause recurrent disease within one year. GBM is almost invariably fatal within a few years after it is diagnosed. Our goal is to achieve long-term control of GBM by combining immunoprophylaxis with a radiation-based technique, such as boron neutron-capture therapy (BNCT), potentially capable of specifically targeting the infiltrating tumor cells while sparing the surrounding normal brain tissue. It has long been known that the subcutaneous (sc) injection of irradiated cells or untreated cultured cells (and the removal of the resulting tumors) derived from the well characterized, highly immunogenic 9L gliosarcoma (9LGS) rat model into young isogenic rats can prevent tumor growth after subsequent sc or intracranial (ic) injection of untreated, otherwise lethal 9LGS cells. In this study we have confirmed, quantified and extended those findings to study the efficacy of such immunological memory in normal aging rats and in aging rats previously treated for ic 9LGS tumors by BNCT. (1) The sc injection of 5,000,000 untreated 9LGS cells and the surgical removal of the resulting tumors (method A) protected 80% of normal young rats from an ic challenge with 10,000 untreated 9LGS cells, and a single sc injection of 5,000,000 lethally X-irradiated 9LGS cells (method B) protected 66% of them, but multiple sc injections with a crude particulate fraction prepared from 9LGS cells were not protective. Protection is long-lasting since contralateral ic rechallenge of six-month survivors with an injection of 10,000 viable 9LGS cells resulted in 100% survival. (2) Normal one-year-old rats were only slightly less protected than were normal young rats, approximately 70% rather than approximately 80% (method A) and approximately 60% rather than approximately 66% (method B). (3) BNCT treatment alone resulted in partial immunological protection, as 30% of one-year post-BNCT survivors of ic 9LGS tumors prevailed after contralateral ic rechallenge with 10,000 viable 9LGS cells. Moreover a single sc immunization with 5,000,000 untreated 9LGS cells prior to ic rechallenge boosted survival from 30% to 100%. The relevance of these observations to strategies of preclinical experimentation for immunoprophylaxis of malignant gliomas is discussed.

Animals↗
PubMed2003

Intradermal vaccination of adults with three low doses (2 micrograms) of recombinant hepatitis B vaccine. II. Persistence of immunity and induction of immunologic memory.

Of the 110 dentists who had presented seroconversion 50 days after the intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine against hepatitis B (HB), administered eight years before at an interval of one month between the 1st and 2nd doses and of five months between the 2nd and 3rd doses, 51 were included for the assessment of the persistence of immunity. None of the dentists had hepatitis or had received HB vaccine during this period. All subjects were submitted to serological tests for the detection of the following markers of hepatitis B virus (HBV) infection: HBsAg, anti-HBc, HBeAg, anti-HBe, and anti-HBs, with no HBsAg, anti-HBc, HBeAg or anti-HBe being detected. A microparticle enzyme immunoassay (MEIA) revealed the presence of anti-HBs at protective titers (> or = 10 mIU/ml) in 42 dentists (82.4%), with the anti-HBs titer being higher than 100 mIU/ml in 36 of them (70.6%) (good responders), between 10 and 100 mIU/ml in 6 (11.8%) (poor responders), and lower than 10 mIU/ml in 9 (17.6%) (non-responders). According to clinical data and serological tests, none of the dentists had presented disease or latent HBV infection during the eight years following the first vaccination. A 2 micrograms booster dose was administered intradermally to eight dentists with anti-HBs titers lower than 10 mIU/ml (non-responders) and to six dentists with titers ranging from 10 to 100 mIU/ml (poor responders); the determination of anti-HBs one month later demonstrated the occurrence of seroconversion in the eight non-responders and an increase in anti-HBs titer in the six poor responders. In summary, the present results demonstrated the prolonged persistence of protection against HBV infection and the development of immunologic memory provided by vaccination against HB--with intradermal application of three 2 micrograms doses of the Belgian recombinant vaccine at 0, 1, and 6 months--carried out eight years before in 51 dentists.

Adult↗
PubMed2006

The conundrum between immunological memory to adenovirus and their use as vectors in clinical gene therapy.

In the context of clinical gene transfer using viral vectors, the risk of memory antivector immunity is often poorly appreciated. The immunological past of the patient, the site of injection, and the vector dose will play intertwined and decisive roles in the safety and efficacy of treatment. To circumvent the drawbacks due to the ubiquitous human adenovirus (HAd) memory immunity, we believe that vectors derived from canine adenovirus type 2 (CAV-2) will be more clinically useful than those derived from HAds based, in part, on the potential lack of immunological memory. CAV-2 is not a human pathogen in spite of the approx 100,000 yr of cohabitation of humans with dogs. During the last 8 yr, we found that CAV-2 vectors preferentially transduced neurons in the central nervous system (CNS) of several species, and had a surprisingly efficient level of axoplasmic transport. CAV-2 vectors also lead to greater than 1 yr transgene expression in the immunocompetent rat CNS-without immunosuppression. However, more immediate harm can be caused to a patient via an acute and/or chronic vector-induced cellular infiltration in the CNS than by the normal progression of most neurodegenerative disorders. In this context, we continue to assess the clinical potential of CAV-2. This mini-review addresses our analysis of the interaction of CAV-2 vectors with human memory immunity and monocyte-derived dendritic cells.

Adenoviruses, Canine↗
PubMed1991

Maintenance of immunological memory: a role for CD5+ B cells?

How memory is retained is an immunological mystery. One possibility, argued here by Fons UytdeHaag and colleagues, is that memory is imprinted in the somatically-mutated Ig expressed by certain CD5+ B cells. The theory proposes that the Ig expressed by this self-renewing population acts as surrogate antigen, selecting and stimulating emerging antigen-specific lymphocytes.

Animals↗
PubMed1966

The carriage of immunological memory by small lymphocytes in the rat.

Lymphocytes were obtained from the thoracic duct of rats 1(1/2) to 15 months after primary immunization with a single dose of bacteriophage phiX 174. An intravenous injection of these lymphocytes conferred on heavily X-irradiated rats the ability to form antibody in a secondary-type manner after a first injection of phiX. Negligible responses were obtained after cell transfer if the recipients were not challenged with antigen. Thoracic duct cells from some immunized donors were incubated in vitro for 24 hr before transfer in order to destroy selectively the large, dividing lymphocytes. The responsiveness conferred on X-irradiated recipients by such "incubated" inocula was then compared with that given by equal numbers of "fresh" thoracic duct cells. In all such comparisons the recipients of the "incubated" cells gave higher and more rapid antibody responses. It was concluded that the cells in thoracic duct lymph which carried immunological memory were small lymphocytes.

Allergy and Immunology↗
PubMed2002

A role for antigen in the maintenance of immunological memory.

The immune system has a memory that it exhibits in the enhanced and augmented responses the second time it meets an antigen. The memory is the result of a number of changes to the system brought about during the primary response. The most important of these changes is the formation of an expanded pool of antigen-specific memory cells. One of the enduring questions in immunology is how these memory cells are maintained for such long periods.

Animals↗
PubMed1968

Cytology of immunologic memory. A morphologic study of lymphoid cells during the anamnestic response.

Pairs of rats were immunized with keyhole limpet hemocyanin (KLH) and simultaneously labeled with thymidine-methyl-(3)H or 5-iodo-2'-deoxyuridine-(125)I. From 10-50 days later, their lymphoid organs were examined 3 days after anamnestic stimulation with KLH or after primary injection of BGG. Light and electron microscopic study of the labeled cells revealed that immunologic memory resided in the mature resting monoribosomal lymphocyte which, upon stimulation, transformed to an immature polyribosomal lymphocyte and mitotically active blast cell. These latter elements differentiated into plasma cells directly or after mitosis.

Animals↗
PubMed1986

Immunological consequences of tumor excision: from active immunity to immunological memory.

Excision of the immunogenic Meth-A fibrosarcoma during generation by the host of concomitant antitumor immunity resulted in the appearance in sequence of two qualitatively distinct states of post-excision immunity. Immunity expressed on the day of excision was dependent on Ly-1-2+, cyclophosphamide-sensitive T cells, whereas immunity expressed 2 weeks later was dependent on cyclophosphamide-resistant T cells which can be functionally eliminated by either anti-Ly-1 or anti-Ly-2 monoclonal antibody and complement. The data suggest that antitumor immunity expressed shortly after tumor excision represents active concomitant immunity that is acquired by the host before excision is performed. In contrast, immunity expressed 2 weeks later is based on immunological memory.

Animals↗
PubMed1971

Maternal-fetal interaction and immunological memory.

Female rats of the poorly responding, inbred F344 strain were immunized with poly(Glu(52)Lys(33)Tyr(15)) aggregated with methylated bovine serum albumin, and then they were mated. The first and second litters in the F(1) generation and in the F(2) generation showed an enhanced immune response. When poly-lysine was used as the aggregating agent, enhancement occurred in only the first litter of the F(1) generation and in the F(2) generation. In both cases, antigen was transmitted from the immunized female to her offspring, where it localized in the bone marrow and, in a few cases, in the thymus and spleen also. The transplacental passage of antigen is probably the basis for the enhanced antibody response, which is a manifestation of immunological memory.

Animals↗