Analysis of Immunocompetent Cells in the Middle Ear Mucosa

Ichimiya, Issei; Kawauchi, Hideyuki; Mogi, Goro

doi:10.1001/archotol.1990.01870030088015

Cited by 62 publications

(44 citation statements)

References 16 publications

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“…19 P6-specific cytokine assay. For the detection of gamma interferon (IFN-␥), interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, and transforming growth factor ␤ (TGF-␤)-specific mRNA in P6-specific CD4 ϩ T cells isolated from MEM, a modified standard reverse transcription-PCR (RT-PCR) amplification protocol was employed (15,16).…”

Section: Analysis and Purification Of T Cells In Memmentioning

confidence: 99%

“…Despite the recent emphasis on a better understanding of molecular and cellular aspects of the mucosal immune system, little information is currently available regarding the middle ear mucosa (MEM). Several histologic studies have indicated that the MEM has a function as a mucosal effector site, as does the nasal mucosa (19,29,36,37,41); however, immune responses by mucosal lymphocytes in the middle ear have not been studied because of the difficulty in isolating cells from the MEM. Recently, we established a method for isolating lymphocytes from the MEM and analyzed mucosal lymphocytes at the single cell level in the middle ear of normal mice.…”

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confidence: 99%

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Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

et al. 2000

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Nontypeable Haemophilus influenzae (NTHI) is a major pathogen of otitis media. One of the outer membrane proteins of NTHI, P6, is an antigen common to all strains and is considered as a candidate for mucosal vaccine. To elucidate the possibility of developing a nasal vaccine against nontypeable Haemophilus influenzae (NTHI) and to investigate mucosal immune responses in the middle ear, mice were immunized intranasally with the P6 outer membrane protein of NTHI, and P6-specific immune responses in the middle ear mucosa were examined. Mice were given with P6 and cholera toxin intranasally as an adjuvant on days 0, 7, and 14 and were killed on day 21. The P6-specific immunoglobulin A (IgA) antibody titer in ear wash was significantly elevated. Mononuclear cells were isolated from middle ear mucosa, and an increase in P6-specific IgA-producing cells was shown with an enzyme-linked immunospot assay. In addition, an increase in memory T cells in middle ear mucosa was detected with flow cytometric analysis after intranasal immunization. Moreover, in vitro stimulation with P6 resulted in proliferation of purified CD4 ؉ T cells from immunized mice, and these T cells expressed Th2 cytokine mRNA. These results indicate that P6-specific IgA-B-cell immune responses and selected Th2 cytokine expressing Th cells were induced in middle ear mucosa by intranasal immunization. These findings suggest that a nasal vaccine is useful for preventing otitis media with effusion.Nontypeable Haemophilus influenzae (NTHI) is a major pathogen of otitis media with effusion (OME) and other upper respiratory tract diseases (10, 30). In patients with OME, this bacterium is frequently isolated from the nasopharynx, as well as from middle ear effusions, and the inhibition of NTHI colonization in the upper respiratory tract is considered effective in preventing OME. Due to the increase of antibiotic-resistant strains of NTHI in recent years, the development of a vaccine against this bacterium is considered an important goal for public health. Since NTHI lacks capsular antigens, the chief antigenicity is present in the outer membrane proteins (OMPs). One of the OMPs of NTHI, P6, is a common antigen to all strains and is considered as a candidate for mucosal vaccine (7,9,10,11,30,31).In the mucosal surface, secretory immunoglobulin A (IgA) plays a major role in protective immunity. We previously demonstrated that intranasal immunization was an effective regimen for inducing mucosal IgA immune responses in the upper respiratory tract (26) and that the nasal mucosal IgA immune responses induced by intranasal immunization were effective for the clearance of bacteria in the nasopharynx.The mucosal immune system is considered as a separate functional entity quite independent of the systemic immune system because the mucosal immune system possesses unique anatomic features and is composed of specialized subsets of lymphoid cells (21,27,34). Despite the recent emphasis on a better understanding of molecular and cellular aspects of the mucosal immune system,...

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Section: Analysis and Purification Of T Cells In Memmentioning

confidence: 99%

mentioning

confidence: 99%

Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

et al. 2000

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“…New vaccines for the prevention of Streptococcus pneumoniae and nontypeable Haemophilus influenzae AOM and other mucosal infections are in development (2, 6, 11, 21, 22). Therefore, the sources of antibody at the site of infection (the middle ear) need to be understood.Although the normal mucosa of the middle ear possesses neither immunocompetent lymphocytes nor associated lymphoid tissues, there are studies which have demonstrated the presence of secretory IgA (sIgA) in middle ear effusions and IgA plasma cells in the mucosa of the middle ear suggesting that a local immune response in the middle ear is possible and may contribute to resolution of or protection from infection (8,9,18). Previous studies have also shown severalfold more IgG antibody compared to IgA antibody in the middle ear, suggesting that antibodies in the middle ear arrive by transudation from serum (33).…”

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confidence: 99%

Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

Kaur¹,

Kim²,

Casey³

et al. 2012

Clin. Vaccine Immunol.

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The human middle ear is devoid of any immunocompetent cells in normal mucosa. We sought to determine the source of antibody present in the middle ear of children. Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of children with acute otitis media. The two-dimensional gel electrophoresis pattern of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid (MEF) was compared from the MEF and NW samples using isoelectric focusing and Western blotting. C olonization of the nasopharynx (NP) by respiratory bacterial pathogens produces both a systemic and a mucosal immune response (1,10,11,15,22,26,38). Local mucosal immunity in the NP plays a crucial role in the reduction of carriage and prevention of local disease (acute otitis media [AOM], sinusitis, and pneumonia) and systemic invasion by respiratory bacteria (4, 16, 20-22, 27, 36). Protective mucosal immune responses are most effectively induced by mucosal immunization through oral and nasal routes but the vast majority of vaccines in use today are administered by injection (19). Parenteral administration of Haemophilus influenzae type b and Streptococcus pneumoniae polysaccharide and polysaccharide-conjugate vaccines can induce a transient mucosal immune response but immunologic memory at the mucosal level is generally not induced (23,24,37).Current pneumococcal conjugate vaccines for prevention of AOM and pneumonia are administered by injection and are considered to be effective by generation of antibody in serum and transudation of antibody to the NP, middle ear, and lung (3,12,25,34,37). New vaccines for the prevention of Streptococcus pneumoniae and nontypeable Haemophilus influenzae AOM and other mucosal infections are in development (2, 6, 11, 21, 22). Therefore, the sources of antibody at the site of infection (the middle ear) need to be understood.Although the normal mucosa of the middle ear possesses neither immunocompetent lymphocytes nor associated lymphoid tissues, there are studies which have demonstrated the presence of secretory IgA (sIgA) in middle ear effusions and IgA plasma cells in the mucosa of the middle ear suggesting that a local immune response in the middle ear is possible and may contribute to resolution of or protection from infection (8,9,18). Previous studies have also shown severalfold more IgG antibody compared to IgA antibody in the middle ear, suggesting that antibodies in the middle ear arrive by transudation from serum (33). In the present study, we evaluated (i) simultaneous concentrations of IgG and IgA in serum, NW, and MEF samples in children with AOM; (ii) simultaneous concentrations of sIgA in NW and MEF samples; and (iii) the electrophoresis pattern of the entire array of IgA antibodies in the MEF and NW to determine whether the antibodies present in middle ear fluid were predominantly derived from serum and the nasal passageways by reflux up the Eustachian tube. MATERIALS AND METHODSPatient popul...

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“…These findings suggest that immune reactions at the time of initial pathogen infection are important in the onset of recurrent otitis media. Particularly, although immune cells such as T and B cells are relatively scarce in the middle ear cavity, this cavity is pathogen free, suggesting that the middle ear cavity is protected by the innate rather than the adaptive immune system (26).…”

Section: Discussionmentioning

confidence: 99%

Expression of Toll-like Receptors 2 and 4 and Immunoglobulins in Children wih Recurrent Otitis Media with Effusion

Lee

Park

et al. 2008

Immune Netw

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Background: Toll-like receptors (TLRs) detect microbial infection and can directly induce innate host defense responses, which are thought to play critical roles in protecting the tubotympanum from infection. However, little is known about the relationship between TLRs, which are related to innate immunity, and immunoglobulins, which are related to adaptive immunity, in recurrent otitis media with effusion (OME). We therefore investigated the expression of TLR2 and TLR4 and immunoglobulin in children with OME. Methods: The study population consisted of 72 children with OME, 31 with more than 4 episodes in 12 months or more than 3 episodes in 6 months (otitis-prone group), and 41 with fewer than 3 episodes in 12 months (non-otitis prone group). The expression in middle ear effusion of TLR2 and TLR4 mRNA, as determined by Real time--polymerase chain reaction (RT-PCR), and the concentrations of IgG, IgA, and IgM, as determined by Enzyme-linked immunosorbent assay(ELISA), were compared between the two groups. Results: Expression of TLR2 and TLR4 mRNA was lower in the otitis prone than in the non-otitis prone group, but the difference was not statistically significant (p＞0.05). Between group differences in the concentrations of IgG, IgA and IgM in effusion fluid were not significant (p>0.05), and there were no correlations between immunoglobulin concentration and the expression of TLR2 and TLR4. Conclusion: Although there was a trend toward lower expression of TLR2 and TLR4 in the otitis-prone group, the differences, and those in immunoglobulin concentration, did not differ significantly between the otitis-prone and non-prone groups.

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Analysis of Immunocompetent Cells in the Middle Ear Mucosa

Cited by 62 publications

References 16 publications

Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

Expression of Toll-like Receptors 2 and 4 and Immunoglobulins in Children wih Recurrent Otitis Media with Effusion

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