Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the pr... more Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the presence and level of interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) by enzyme immunoassay. The expression of these cytokine mRNAs in milk macrophages from eight donors were semiquantitatively analyzed by reverse transcriptase-polymerase chain reaction. The effects of respiratory syncytial virus (RSV) infection on cytokine production were determined in five samples of milk macrophages. Over 90% of the milk samples tested exhibited detectable levels of IL-1β, IL-6, and TNF-α. No IL-12 or IFN-γ activity was detected in the milk. IL-6 activity was weakly detected in about 45%, and TNF-α activity in about 10% of the serum samples tested. However, no IL-1β, IL-12, or IFN-γ activity was demonstrated in any of the serum samples. Milk macrophages from eight subjects all exhibited mRNA for IL-1β, TNF-α, and IL-6, and IFN-γ mRNA in six of eight subjects, ...
Groups of lactating BALB/c mice were immunized in the immediate postpartum period with high doses... more Groups of lactating BALB/c mice were immunized in the immediate postpartum period with high doses of mAb (Ab-1) to the F-glycoprotein (F-gp) of respiratory syncytial virus (RSV). This antibody possessed neutralizing activity against the whole virus. The immune response to F-gp was studied in the breast feeding infant mice of such mothers at regular intervals before and after weaning. All infant mice exhibited anti-F-gp activity in serum, which was detected until 6 wk of age. Splenic cells of such breast feeding infant mice collected after weaning exhibited in vitro synthesis of antibody against Ab-1, the antibody previously used for maternal immunization. Subsequent immunization with homologous purified RSV F-gp resulted in a booster response for IgG, IgM, and plaque-neutralizing antibody to the immunizing RSV protein and to the whole virus in the infants primed via breast feeding. The enhanced antibody response was specific for the antigenic epitopes of the virus protein recognized...
Journal of immunology (Baltimore, Md. : 1950), 1987
Analysis of an earlier study of H3N2 and H7N2 inactivated influenza vaccines in schoolchildren de... more Analysis of an earlier study of H3N2 and H7N2 inactivated influenza vaccines in schoolchildren demonstrated a greater viral neuraminidase (NA) immunogenicity of the vaccine containing the H7 hemagglutinin (HA) antigen to which they had not been primed, despite the lesser NA antigen content of that vaccine. Thus, prior experience with the influenza viral HA appeared to have a negative influence on immune response to NA, the associated external glycoprotein, presumably on the basis of intermolecular antigenic competition. In a second study, sequential immunologic response to influenza viral NA was compared in college students who were immunized with either conventional commercial vaccine or an antigenic reassortant H7N1 vaccine, and who subsequently experienced natural infection with an H1N1 influenza virus. Although both vaccines were only marginally immunogenic in inducing NA antibody response in seronegative subjects, in vaccinees initially seropositive for HA antibody significant ...
The worldwide impact of rotaviruses (RV) as the leading cause of diarrhea in children has generat... more The worldwide impact of rotaviruses (RV) as the leading cause of diarrhea in children has generated much interest in disease prevention by a specific vaccine. The Jennerian approach to RV vaccination of humans using orally administered heterologous (animal) strains has been the most promising [1]. The suckling mouse model has recently been shown to be applicable to study the disease induced by heterologous RVs [2]. Mice with severe combined immunodeficiency (SCID), which are known to suffer persistent murine RV infection, constitute a good model for the immunocompromised host. Recent studies in our laboratory have suggested that mucosal immunocompetence may play an important role in influencing heterologous RV infection in mice [3]. This was evidenced by extramucosal spread and hepatic virus replication of rhesus RV (RRV) in SCID mice. The aim of this study was to examine the effect of different routes of administration on the hepatopathogenic potential of RRV in SCID and normal mice.
Infection with RSV is a major cause for hospitalizations of infants in the first year of life in ... more Infection with RSV is a major cause for hospitalizations of infants in the first year of life in the United States and most other parts of the world. Almost 100% of children are infected with this virus by 2-3 years of age. Normally, the infection is exquisitely restricted to the bronchopulmonary mucosa. However, development of extrapulmonary disease is observed in patients with certain T and B cell immunodeficiency states. The spectrum of illness associated with RSV is diverse and ranges from asymptomatic infection, mild upper airway disease, otitis media, apnea in the early neonatal period, or severe respiratory tract disease associated with bronchiolitis, pneumonia, wheezing or sudden infant death syndrome (SIDS). A small number of children will develop long term abnormalities of pulmonary function, episodes of wheezing or established reactive airway disease after severe disease or bronchiolitis. The immune response to primary infection is modest at best, but reinfection is follo...
Advances in Experimental Medicine and Biology, 1995
In 1988, two groups of investigators reported the successful adoptive transfer of nonneoplastic h... more In 1988, two groups of investigators reported the successful adoptive transfer of nonneoplastic human cells into mice with severe combined immunodeficiency (SCID).1–3 These mice originated from the CB-17 lcr strain by a spontaneous autosomal recessive mutation4 affecting the VDJ recombinase system.5 SCID mice lack functional B and T cells, but have a normal arsenal of macrophages and NK cells. The survival of human immunoreactive cells in SCID mice allows for the study of the human immune system in an animal model. Thus the human immune system is available for experimental protocols feasible up to now only for the study of animal immune systems. SCID mice engrafted with human immunologically reactive cells were called “human-mouse chimeras,” “SCID-hu mice” and, hu-SCID mice. These mice are of interest for the study of maturation and differentiation of human hematopoietic cells,6 tumor immunology,7,8 human immune responses to infectious agents, neoplasms and autoantigens,9,10 and drug effects on the human immune system. The hu-SCID mouse also seems an exciting model for the direct study of components of human mucosa-associated lymphoid tissue (MALT), their interactions, functions, and traffic in vivo.11,12
A comparison of three assays for the detection of serum antibody to respiratory syncytial virus (... more A comparison of three assays for the detection of serum antibody to respiratory syncytial virus (RSV) was carried out on 47 serum samples obtained sequentially from infants and young children with RSV infection. Neutralizing-antibody (NA) activity was determined by a semimicromethod of plaque reduction. Complement-enhanced NA activity was determined by the addition of guinea pig complement to NA assays. RSV antibody responses in immunoglobulin G, immunoglobulin M, and immunoglobulin A classes were determined by using indirect immunofluorescence techniques for fluorescent-antibody (FAb) assay. Antibody to RSV was detectable by all three techniques as early as 4 days after the onset of illness. At all phases of illness, titers obtained by complement-enhanced NA assays were significantly greater than those obtained by NA or FAb assays (P less than 0.01). RSV-FAb titers determined in the immunoglobulin G class correlated well with those determined by complement-enhanced NA or NA assays....
Reovirus, serotype 1, causes a transient, asymptomatic infection of the murine intestine when giv... more Reovirus, serotype 1, causes a transient, asymptomatic infection of the murine intestine when given intraduodenally or orally. However, this infection markedly perturbs both B- and T- cell populations in Peyer's patches (PP) resulting in: 1) a rapid and persistent increase in specific precursors for cytotoxic T cells (pCTL) and a gradient of frequencies highest in PP and lowest in distal lymphoid tissue; 2) a similar increase in memory B cells committed to IgA; 3) the transient appearance of a subset of germinal center B cells identified by MAb, GC-T; 4) the appearance of pCTL among intraepithelial lymphocytes; and 5) the antigen non-specific alteration in Ig isotype potential of B cells previously primed and found in PP. The pCTL appearing upon acute gut mucosal infection with reovirus are Thyl+, Lyt2+, virus-specific, viral serotype non-specific, class I MHC haplotype restricted and occur within the subset of T cells which newly appears also identified by MAb GC-T. Infections of both neonatal and severe-combined immunodeficient mice indicate that the elements of the immune system may operate at many levels to resist, limit, contain, and resolve viral infection.
The rubella-specific antibody, activity the levels of immunoglobulins and complement in the serum... more The rubella-specific antibody, activity the levels of immunoglobulins and complement in the serum, the number of T cells, and the nature of cell-mediated immunity as measured by lymphocyte transformation (LTF) of circulating lymphocytes in response to rubella virus and phyto-hemagglutinin (PHA) were studied in 15 children who manifested arthralgia or arthritis after parenteral immunization with HPV-77 DE/5 or RA27/3 live attenuated rubella virus vaccines. Eighteen appropriately matched subjects who developed no post-vaccine complications were included as controls. The immunoglobulins, complement, and rubella antibody levels were similar in all subjects. Although significant rubella specific cell-mediated immunity was detectable in most control subjects, the activity was markedly depressed in subjects with arthritis. The LTF activity in response to PHA was approximately equal in both groups. These findings suggest a selective depression of cell-mediated immunity to rubella virus in s...
Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transfor... more Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation (LTF), we studied the humoral antibody and cell-mediated immunity to cytomegalovirus (CMV) in normal subjects, in patients with cancer receiving localized or nonlocalized radiation, and in renal transplant recipients on immunosuppressive chemotherapy. The LTF activity was determined by the whole blood microassay, using four strains of CMV (AD-169, Davis, Veca, and Towne), AD-169 early antigen, and phytohemagglutinin (PAH). The renal transplant subjects manifested significantly depressed LTF responses to PHA and CMV and frequent presence of immunoglobulin M and early antigen-specific antibody response. The depressed LTF response to CMV recovered significantly 2 years after transplantation. The cancer patients were also characterized by a profound drop in LTF responses to PHA and CMV and in immunoglobulin M and early antigen-specific antibody response after nonlocalized radiation. L...
A group of formula-fed infants were administered a single feed of poliovirus IgA antibody-rich hu... more A group of formula-fed infants were administered a single feed of poliovirus IgA antibody-rich human colostrum 18 to 72 hr after birth. Subsequently, the presence of IgG, IgA, and IgM immunoglobulin and poliovirus antibody activity was determined in serial serum and fecal samples of the neonates. Absorption of IgA immunoglobulin from the colostrum to the circulation was observed in three infants who were fed with colostrum between 18 and 24 hr after birth. Another group of infants of tuberculin-positive mothers who were being breast fed by their own mothers were followed for the development of in vitro correlates of cell-mediated immunity against tuberculin after prolonged breast feeding. Tuberculin-specific proliferative response was observed in the peripheral blood lymphocytes of two neonates after 5 weeks of breast feeding. The responses were undetectable after 12 weeks, although the infants continued to breast feed. No tuberculin reactivity was observed in the cord lymphocytes. ...
The protective effect of a human strain of Bifidobacterium bifidum (B. bifidum) against murine Gr... more The protective effect of a human strain of Bifidobacterium bifidum (B. bifidum) against murine Group A rotavirus (MRV) was examined in the intestines of BALB/c infected mice. In experiments designed to determine whether B. bifidum mediated MRV shedding during diarrheal disease, pregnant dams (and their expected litters) were randomly assigned to the following groups: 1. Mice infected with MRV alone; 2. B. bifidum treated + MRV infected mice; 3. B. bifidum treated controls; 4. Saline control animals. An enzyme-linked immunosorbent assay (ELISA) for the detection of group A rotavirus was used to measure virus protein. Treatment with B. bifidum significantly reduced shedding of MRV antigen (P < 0.009) days 2-10 post-inoculation. The reduction in shedding of virus protein corresponded well with delayed onset of acute diarrhea (P < 0.02). Closer examination of tissue cross-sections under electron microscopy revealed that the B. bifidum ingested strain adhered to the epithelium of t...
The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006... more The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006 and bovine rotavirus strain WC3, were evaluated in mice with severe combined immunodeficiency (SCID mice) and normal BALB/c mice. Control animals were inoculated with homologous murine strain EDIM 5099 or a tissue culture-adapted murine rotavirus. Heterologous infection with rhesus rotavirus resulted in hepatitis in 84% of SCID and 21% of BALB/c mice, with mortality rates of 27 and 0%, respectively. Surviving SCID animals developed chronic liver disease, while symptoms in BALB/c mice resolved in 2 to 4 weeks after onset. Histopathologic examination revealed a diffuse hepatitis with focal areas of parenchymal necrosis. Rotavirus was detected in liver tissue from 100% of 29 SCID and 85% (11 of 13) BALB/c animals tested by cell culture infectivity, immunofluorescence, or electron microscopy. No extramucosal spread of virus or hepatitis was observed after infection with heterologous bovine ...
The involvement of external mucosal surfaces in the mechanism of defense against pathogenic micro... more The involvement of external mucosal surfaces in the mechanism of defense against pathogenic microorganisms has recently attracted much attention. Many infectious agents gain access to the human body through the mucosa of nasopharynx, respiratory, genitourinary or lower gastrointestinal tracts. The immunocompetent lymphoid tissue in the mucosal portal of entry plays an important role in the mucosal immune system. The nasopharyngeal mucosa, tonsils and adenoids are replete with immunocompetent tissue. Because of their strategic anatomic location these tissues are in a relatively intimate and constant contact with the external environment, and constitute the primary sites of initial exposure to inhaled or ingested antigens. In addition to the "gatekeeper" site and function of the tonsils and adenoids, the tonsillar lymphoid tissue may also be involved in the overall development of the human immune system. This review will briefly focus on the immunologic consideration of the nasopharynx and tonsils, and examine the possible role of tonsils in the mechanisms of.local immunity.
Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the pr... more Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the presence and level of interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) by enzyme immunoassay. The expression of these cytokine mRNAs in milk macrophages from eight donors were semiquantitatively analyzed by reverse transcriptase-polymerase chain reaction. The effects of respiratory syncytial virus (RSV) infection on cytokine production were determined in five samples of milk macrophages. Over 90% of the milk samples tested exhibited detectable levels of IL-1β, IL-6, and TNF-α. No IL-12 or IFN-γ activity was detected in the milk. IL-6 activity was weakly detected in about 45%, and TNF-α activity in about 10% of the serum samples tested. However, no IL-1β, IL-12, or IFN-γ activity was demonstrated in any of the serum samples. Milk macrophages from eight subjects all exhibited mRNA for IL-1β, TNF-α, and IL-6, and IFN-γ mRNA in six of eight subjects, ...
Groups of lactating BALB/c mice were immunized in the immediate postpartum period with high doses... more Groups of lactating BALB/c mice were immunized in the immediate postpartum period with high doses of mAb (Ab-1) to the F-glycoprotein (F-gp) of respiratory syncytial virus (RSV). This antibody possessed neutralizing activity against the whole virus. The immune response to F-gp was studied in the breast feeding infant mice of such mothers at regular intervals before and after weaning. All infant mice exhibited anti-F-gp activity in serum, which was detected until 6 wk of age. Splenic cells of such breast feeding infant mice collected after weaning exhibited in vitro synthesis of antibody against Ab-1, the antibody previously used for maternal immunization. Subsequent immunization with homologous purified RSV F-gp resulted in a booster response for IgG, IgM, and plaque-neutralizing antibody to the immunizing RSV protein and to the whole virus in the infants primed via breast feeding. The enhanced antibody response was specific for the antigenic epitopes of the virus protein recognized...
Journal of immunology (Baltimore, Md. : 1950), 1987
Analysis of an earlier study of H3N2 and H7N2 inactivated influenza vaccines in schoolchildren de... more Analysis of an earlier study of H3N2 and H7N2 inactivated influenza vaccines in schoolchildren demonstrated a greater viral neuraminidase (NA) immunogenicity of the vaccine containing the H7 hemagglutinin (HA) antigen to which they had not been primed, despite the lesser NA antigen content of that vaccine. Thus, prior experience with the influenza viral HA appeared to have a negative influence on immune response to NA, the associated external glycoprotein, presumably on the basis of intermolecular antigenic competition. In a second study, sequential immunologic response to influenza viral NA was compared in college students who were immunized with either conventional commercial vaccine or an antigenic reassortant H7N1 vaccine, and who subsequently experienced natural infection with an H1N1 influenza virus. Although both vaccines were only marginally immunogenic in inducing NA antibody response in seronegative subjects, in vaccinees initially seropositive for HA antibody significant ...
The worldwide impact of rotaviruses (RV) as the leading cause of diarrhea in children has generat... more The worldwide impact of rotaviruses (RV) as the leading cause of diarrhea in children has generated much interest in disease prevention by a specific vaccine. The Jennerian approach to RV vaccination of humans using orally administered heterologous (animal) strains has been the most promising [1]. The suckling mouse model has recently been shown to be applicable to study the disease induced by heterologous RVs [2]. Mice with severe combined immunodeficiency (SCID), which are known to suffer persistent murine RV infection, constitute a good model for the immunocompromised host. Recent studies in our laboratory have suggested that mucosal immunocompetence may play an important role in influencing heterologous RV infection in mice [3]. This was evidenced by extramucosal spread and hepatic virus replication of rhesus RV (RRV) in SCID mice. The aim of this study was to examine the effect of different routes of administration on the hepatopathogenic potential of RRV in SCID and normal mice.
Infection with RSV is a major cause for hospitalizations of infants in the first year of life in ... more Infection with RSV is a major cause for hospitalizations of infants in the first year of life in the United States and most other parts of the world. Almost 100% of children are infected with this virus by 2-3 years of age. Normally, the infection is exquisitely restricted to the bronchopulmonary mucosa. However, development of extrapulmonary disease is observed in patients with certain T and B cell immunodeficiency states. The spectrum of illness associated with RSV is diverse and ranges from asymptomatic infection, mild upper airway disease, otitis media, apnea in the early neonatal period, or severe respiratory tract disease associated with bronchiolitis, pneumonia, wheezing or sudden infant death syndrome (SIDS). A small number of children will develop long term abnormalities of pulmonary function, episodes of wheezing or established reactive airway disease after severe disease or bronchiolitis. The immune response to primary infection is modest at best, but reinfection is follo...
Advances in Experimental Medicine and Biology, 1995
In 1988, two groups of investigators reported the successful adoptive transfer of nonneoplastic h... more In 1988, two groups of investigators reported the successful adoptive transfer of nonneoplastic human cells into mice with severe combined immunodeficiency (SCID).1–3 These mice originated from the CB-17 lcr strain by a spontaneous autosomal recessive mutation4 affecting the VDJ recombinase system.5 SCID mice lack functional B and T cells, but have a normal arsenal of macrophages and NK cells. The survival of human immunoreactive cells in SCID mice allows for the study of the human immune system in an animal model. Thus the human immune system is available for experimental protocols feasible up to now only for the study of animal immune systems. SCID mice engrafted with human immunologically reactive cells were called “human-mouse chimeras,” “SCID-hu mice” and, hu-SCID mice. These mice are of interest for the study of maturation and differentiation of human hematopoietic cells,6 tumor immunology,7,8 human immune responses to infectious agents, neoplasms and autoantigens,9,10 and drug effects on the human immune system. The hu-SCID mouse also seems an exciting model for the direct study of components of human mucosa-associated lymphoid tissue (MALT), their interactions, functions, and traffic in vivo.11,12
A comparison of three assays for the detection of serum antibody to respiratory syncytial virus (... more A comparison of three assays for the detection of serum antibody to respiratory syncytial virus (RSV) was carried out on 47 serum samples obtained sequentially from infants and young children with RSV infection. Neutralizing-antibody (NA) activity was determined by a semimicromethod of plaque reduction. Complement-enhanced NA activity was determined by the addition of guinea pig complement to NA assays. RSV antibody responses in immunoglobulin G, immunoglobulin M, and immunoglobulin A classes were determined by using indirect immunofluorescence techniques for fluorescent-antibody (FAb) assay. Antibody to RSV was detectable by all three techniques as early as 4 days after the onset of illness. At all phases of illness, titers obtained by complement-enhanced NA assays were significantly greater than those obtained by NA or FAb assays (P less than 0.01). RSV-FAb titers determined in the immunoglobulin G class correlated well with those determined by complement-enhanced NA or NA assays....
Reovirus, serotype 1, causes a transient, asymptomatic infection of the murine intestine when giv... more Reovirus, serotype 1, causes a transient, asymptomatic infection of the murine intestine when given intraduodenally or orally. However, this infection markedly perturbs both B- and T- cell populations in Peyer's patches (PP) resulting in: 1) a rapid and persistent increase in specific precursors for cytotoxic T cells (pCTL) and a gradient of frequencies highest in PP and lowest in distal lymphoid tissue; 2) a similar increase in memory B cells committed to IgA; 3) the transient appearance of a subset of germinal center B cells identified by MAb, GC-T; 4) the appearance of pCTL among intraepithelial lymphocytes; and 5) the antigen non-specific alteration in Ig isotype potential of B cells previously primed and found in PP. The pCTL appearing upon acute gut mucosal infection with reovirus are Thyl+, Lyt2+, virus-specific, viral serotype non-specific, class I MHC haplotype restricted and occur within the subset of T cells which newly appears also identified by MAb GC-T. Infections of both neonatal and severe-combined immunodeficient mice indicate that the elements of the immune system may operate at many levels to resist, limit, contain, and resolve viral infection.
The rubella-specific antibody, activity the levels of immunoglobulins and complement in the serum... more The rubella-specific antibody, activity the levels of immunoglobulins and complement in the serum, the number of T cells, and the nature of cell-mediated immunity as measured by lymphocyte transformation (LTF) of circulating lymphocytes in response to rubella virus and phyto-hemagglutinin (PHA) were studied in 15 children who manifested arthralgia or arthritis after parenteral immunization with HPV-77 DE/5 or RA27/3 live attenuated rubella virus vaccines. Eighteen appropriately matched subjects who developed no post-vaccine complications were included as controls. The immunoglobulins, complement, and rubella antibody levels were similar in all subjects. Although significant rubella specific cell-mediated immunity was detectable in most control subjects, the activity was markedly depressed in subjects with arthritis. The LTF activity in response to PHA was approximately equal in both groups. These findings suggest a selective depression of cell-mediated immunity to rubella virus in s...
Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transfor... more Using the techniques of complement fixation, immunofluorescence, and in vitro lymphocyte transformation (LTF), we studied the humoral antibody and cell-mediated immunity to cytomegalovirus (CMV) in normal subjects, in patients with cancer receiving localized or nonlocalized radiation, and in renal transplant recipients on immunosuppressive chemotherapy. The LTF activity was determined by the whole blood microassay, using four strains of CMV (AD-169, Davis, Veca, and Towne), AD-169 early antigen, and phytohemagglutinin (PAH). The renal transplant subjects manifested significantly depressed LTF responses to PHA and CMV and frequent presence of immunoglobulin M and early antigen-specific antibody response. The depressed LTF response to CMV recovered significantly 2 years after transplantation. The cancer patients were also characterized by a profound drop in LTF responses to PHA and CMV and in immunoglobulin M and early antigen-specific antibody response after nonlocalized radiation. L...
A group of formula-fed infants were administered a single feed of poliovirus IgA antibody-rich hu... more A group of formula-fed infants were administered a single feed of poliovirus IgA antibody-rich human colostrum 18 to 72 hr after birth. Subsequently, the presence of IgG, IgA, and IgM immunoglobulin and poliovirus antibody activity was determined in serial serum and fecal samples of the neonates. Absorption of IgA immunoglobulin from the colostrum to the circulation was observed in three infants who were fed with colostrum between 18 and 24 hr after birth. Another group of infants of tuberculin-positive mothers who were being breast fed by their own mothers were followed for the development of in vitro correlates of cell-mediated immunity against tuberculin after prolonged breast feeding. Tuberculin-specific proliferative response was observed in the peripheral blood lymphocytes of two neonates after 5 weeks of breast feeding. The responses were undetectable after 12 weeks, although the infants continued to breast feed. No tuberculin reactivity was observed in the cord lymphocytes. ...
The protective effect of a human strain of Bifidobacterium bifidum (B. bifidum) against murine Gr... more The protective effect of a human strain of Bifidobacterium bifidum (B. bifidum) against murine Group A rotavirus (MRV) was examined in the intestines of BALB/c infected mice. In experiments designed to determine whether B. bifidum mediated MRV shedding during diarrheal disease, pregnant dams (and their expected litters) were randomly assigned to the following groups: 1. Mice infected with MRV alone; 2. B. bifidum treated + MRV infected mice; 3. B. bifidum treated controls; 4. Saline control animals. An enzyme-linked immunosorbent assay (ELISA) for the detection of group A rotavirus was used to measure virus protein. Treatment with B. bifidum significantly reduced shedding of MRV antigen (P < 0.009) days 2-10 post-inoculation. The reduction in shedding of virus protein corresponded well with delayed onset of acute diarrhea (P < 0.02). Closer examination of tissue cross-sections under electron microscopy revealed that the B. bifidum ingested strain adhered to the epithelium of t...
The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006... more The pathogenic profiles of two heterologous animal rotaviruses, rhesus rotavirus strain MMU 18006 and bovine rotavirus strain WC3, were evaluated in mice with severe combined immunodeficiency (SCID mice) and normal BALB/c mice. Control animals were inoculated with homologous murine strain EDIM 5099 or a tissue culture-adapted murine rotavirus. Heterologous infection with rhesus rotavirus resulted in hepatitis in 84% of SCID and 21% of BALB/c mice, with mortality rates of 27 and 0%, respectively. Surviving SCID animals developed chronic liver disease, while symptoms in BALB/c mice resolved in 2 to 4 weeks after onset. Histopathologic examination revealed a diffuse hepatitis with focal areas of parenchymal necrosis. Rotavirus was detected in liver tissue from 100% of 29 SCID and 85% (11 of 13) BALB/c animals tested by cell culture infectivity, immunofluorescence, or electron microscopy. No extramucosal spread of virus or hepatitis was observed after infection with heterologous bovine ...
The involvement of external mucosal surfaces in the mechanism of defense against pathogenic micro... more The involvement of external mucosal surfaces in the mechanism of defense against pathogenic microorganisms has recently attracted much attention. Many infectious agents gain access to the human body through the mucosa of nasopharynx, respiratory, genitourinary or lower gastrointestinal tracts. The immunocompetent lymphoid tissue in the mucosal portal of entry plays an important role in the mucosal immune system. The nasopharyngeal mucosa, tonsils and adenoids are replete with immunocompetent tissue. Because of their strategic anatomic location these tissues are in a relatively intimate and constant contact with the external environment, and constitute the primary sites of initial exposure to inhaled or ingested antigens. In addition to the "gatekeeper" site and function of the tonsils and adenoids, the tonsillar lymphoid tissue may also be involved in the overall development of the human immune system. This review will briefly focus on the immunologic consideration of the nasopharynx and tonsils, and examine the possible role of tonsils in the mechanisms of.local immunity.
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