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MeSH Review

Haemophilus influenzae type b

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Disease relevance of Haemophilus influenzae type b

  • In the children with IgG2 deficiency, serum antibody concentrations to the capsular polysaccharide of Hemophilus influenzae type B (Hib) were significantly lower than those in age-matched controls, both before and after immunization with the Hib capsular polysaccharide antigen, which elicits antibody predominantly of the IgG2 subclass [1].
  • We conclude that TNF participates in mediating meningeal inflammation associated with Hib experimental meningitis, and that DXM, when given before or with Hib LOS, inhibits CSF TNF production and modulates the meningeal inflammatory response [2].
  • The aim of the current study is to investigate the effect of human serum IgA on the release of inflammatory cytokines in human monocytes activated with a particulate stimulus, Haemophilus influenzae type b (Hib), or soluble lipopolysaccharide (LPS) purified from Escherichia coli [3].
  • Two post-vaccination pools were prepared from sera of infants vaccinated with either Hib PS oligomers coupled to CRM197, a mutant diphtheria toxin (HbOC), or with higher m.w. Hib PS coupled to an outer membrane protein complex of Neisseria meningitidis group B (Hib-OMP) [4].
  • The C3 epitope of the poliovirus VP1 capsid protein was inserted either into loop 3 or into loop 4 of Hib porin [5].

Psychiatry related information on Haemophilus influenzae type b

  • The human Ab repertoire to the Haemophilus influenzae type b (Hib) polysaccharide (PS) is dominated by Abs that use the kappa II-A2 VL region and that express an idiotype (Id) designated Hibld-1 [6].

High impact information on Haemophilus influenzae type b

  • We also investigated expression of the Hib idiotype 1 (Hibld-1), a serological marker of a VKII chain that comprises a major portion of the normal variable region repertoire of the antibody response to Hib polysaccharide [7].
  • Human adults given single subcutaneous injections had rises in serum Ab to PRP and in bactericidal activity in vitro; the Ab protected infant rats challenged with Hib [8].
  • A 7-day course of ampicillin, cefotaxime, or ceftriaxone is sufficient in Hib, Mnc, or Pnc meningitis [9].
  • Furthermore, this Hib mutant was unable to utilize heme-human hemopexin as a heme source [10].
  • Hib-OMPC was significantly less immunogenic in TLR2 KO mice, inducing lower Hib PS IgG and IgM titers compared with those in wild-type mice [11].

Chemical compound and disease context of Haemophilus influenzae type b

  • Dexamethasone (DXM) (1 mg/kg per i.v.) given 1 h before or simultaneously with IC Hib LOS reduced significantly TNF activity and meningeal inflammation [2].
  • In patients with Hib meningitis, sterilisation of the cerebrospinal fluid occurred most rapidly with ceftriaxone [9].
  • These findings suggest an essential requirement for this conserved Arg residue in determining Hib PS-binding affinity [12].
  • Fabs having A2-Jkappa1 L chains with glutamate or aspartate at 95a or with no junctional residue showed little or no Hib PS binding [12].
  • Digestions of Hib porin with cyanogen bromide, hydroxylamine or trypsin generated fragments, the identities of which were confirmed by microsequencing of the amino termini [13].

Biological context of Haemophilus influenzae type b


Anatomical context of Haemophilus influenzae type b

  • Immune lymphocytes were harvested 7 days after immunization with either of two vaccine formulations, a plain polysaccharide vaccine (Hib PS) or a polysaccharide-protein conjugate of Hib PS and diphtheria toxoid (Hib PS-D) [18].
  • Glycopeptide immunogens were constructed by coupling synthetic oligosaccharides comprising repeating units of synthetic 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate (sPRP) to synthetic peptides containing potent T-helper cell determinants and B-cell epitopes of the Haemophilus influenzae type b (Hib) outer membrane proteins (OMPs) P1, P2, and P6 [19].
  • These observations suggest that ceftriaxone-induced killing of Hib results in bacterial cell wall products that are more proinflammatory than those produced by imipenem [20].
  • A panel of hybridomas secreting human antibodies specific for Hib capsular polysaccharide was developed using peripheral blood lymphocytes from donors immunized with Hib vaccines [21].
  • One T-cell population also proliferated to proteinase K-treated Hib antigen, suggesting that it recognized a nonpeptide [22].

Gene context of Haemophilus influenzae type b

  • ICAM-1 deficiency may be protective early in Hib infection but has a detrimental effect in S. pneumoniae infection [23].
  • When Hib was used, animals were treated with ceftriaxone and dexamethasone with or without IL-10 (1 mg/kg) [24].
  • We found no significant associations with Hib disease for the single alleles of HLA-A, -B, -C, -DR, Gm, Km, Am, Kidd, MNSs, ABO, esterase D, or glutamate pyruvate transaminase loci [25].
  • In addition, triggering of Fc alpha R with MoAb specifically down-regulated TNF-alpha and IL-6 release in human monocytes activated with Hib [26].
  • More recently, a relatively common deficiency of one isotype of C4 (C4B) has been shown to be associated with invasive Hib disease, suggesting that defects in complement-mediated host defense may be more common in systemic Hib infections than previously appreciated [27].

Analytical, diagnostic and therapeutic context of Haemophilus influenzae type b

  • Vaccination against Haemophilus influenzae type b (Hib) diseases began a quarter of a century ago with a polysaccharide vaccine; this vaccine was followed by four different conjugates 10 years later [28].
  • Southern blot analysis of chromosomal DNA from four Hib and four non-typeable H. influenzae (NTHI) strains detected the presence of a single band in each strain that hybridized a Hib hxuA gene probe [14].
  • Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants [29].
  • The role of antibodies against outer membrane proteins (OMP) in the pathogenesis of these diseases was investigated by Western blotting (immunoblotting) with an OMP antigen prepared from a local Hib strain [30].
  • Our aim was to determine the isotype and idiotype distribution and cross-reactivity of natural antibodies against Hib capsular polysaccharide (CP) in healthy Hong Kong Chinese. Titration of 20 sera by ELISA showed IgG antibodies reacting with Hib CP in all individuals [31].


  1. Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency. Umetsu, D.T., Ambrosino, D.M., Quinti, I., Siber, G.R., Geha, R.S. N. Engl. J. Med. (1985) [Pubmed]
  2. Tumor necrosis factor in mediating experimental Haemophilus influenzae type B meningitis. Mustafa, M.M., Ramilo, O., Olsen, K.D., Franklin, P.S., Hansen, E.J., Beutler, B., McCracken, G.H. J. Clin. Invest. (1989) [Pubmed]
  3. Human serum IgA downregulates the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) in human monocytes. Wolf, H.M., Fischer, M.B., Pühringer, H., Samstag, A., Vogel, E., Eibl, M.M. Blood (1994) [Pubmed]
  4. Functional differences in idiotypically defined IgG1 anti-polysaccharide antibodies elicited by vaccination with Haemophilus influenzae type B polysaccharide-protein conjugates. Lucas, A.H., Granoff, D.M. J. Immunol. (1995) [Pubmed]
  5. Porins of Haemophilus influenzae type b mutated in loop 3 and in loop 4. Srikumar, R., Dahan, D., Arhin, F.F., Tawa, P., Diederichs, K., Coulton, J.W. J. Biol. Chem. (1997) [Pubmed]
  6. Induction of a protective human polysaccharide-specific antibody response in hu-PBL SCID mice by idiotypic vaccination. Reason, D.C., Kitamura, M.Y., Lucas, A.H. J. Immunol. (1994) [Pubmed]
  7. Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine. The Collaborative Study Group. Holmes, S.J., Lucas, A.H., Osterholm, M.T., Froeschle, J.E., Granoff, D.M. JAMA (1991) [Pubmed]
  8. Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae type b coupled to diphtheria toxoid or the toxin protein CRM197. Anderson, P., Pichichero, M.E., Insel, R.A. J. Clin. Invest. (1985) [Pubmed]
  9. Randomised comparison of chloramphenicol, ampicillin, cefotaxime, and ceftriaxone for childhood bacterial meningitis. Finnish Study Group. Peltola, H., Anttila, M., Renkonen, O.V. Lancet (1989) [Pubmed]
  10. Identification of a genetic locus of Haemophilus influenzae type b necessary for the binding and utilization of heme bound to human hemopexin. Hanson, M.S., Pelzel, S.E., Latimer, J., Muller-Eberhard, U., Hansen, E.J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  11. Haemophilus influenzae type b-outer membrane protein complex glycoconjugate vaccine induces cytokine production by engaging human toll-like receptor 2 (TLR2) and requires the presence of TLR2 for optimal immunogenicity. Latz, E., Franko, J., Golenbock, D.T., Schreiber, J.R. J. Immunol. (2004) [Pubmed]
  12. Role of kappa II-A2 light chain CDR-3 junctional residues in human antibody binding to the Haemophilus influenzae type b polysaccharide. Lucas, A.H., Moulton, K.D., Reason, D.C. J. Immunol. (1998) [Pubmed]
  13. Monoclonal antibodies specific to porin of Haemophilus influenzae type b: localization of their cognate epitopes and tests of their biological activities. Srikumar, R., Chin, A.C., Vachon, V., Richardson, C.D., Ratcliffe, M.J., Saarinen, L., Käyhty, H., Mäkelä, P.H., Coulton, J.W. Mol. Microbiol. (1992) [Pubmed]
  14. The 100 kDa haem:haemopexin-binding protein of Haemophilus influenzae: structure and localization. Cope, L.D., Thomas, S.E., Latimer, J.L., Slaughter, C.A., Müller-Eberhard, U., Hansen, E.J. Mol. Microbiol. (1994) [Pubmed]
  15. Effect of piliation on interactions of Haemophilus influenzae type b with human polymorphonuclear leukocytes. Tosi, M.F., Anderson, D.C., Barrish, J., Mason, E.O., Kaplan, S.L. Infect. Immun. (1985) [Pubmed]
  16. Immunological properties of recombinant porin of Haemophilus influenzae type b expressed in Bacillus subtilis. Srikumar, R., Dahan, D., Gras, M.F., Saarinen, L., Käyhty, H., Sarvas, M., Vogel, L., Coulton, J.W. Infect. Immun. (1993) [Pubmed]
  17. Avidity maturation of antibody to Haemophilus influenzae type b (Hib) after immunization with diphtheria-tetanus-acellular pertussis-hib-hepatitis B combined vaccine in infants. Pichichero, M.E., Voloshen, T., Zajac, D., Passador, S. J. Infect. Dis. (1999) [Pubmed]
  18. Restricted Ig H chain V gene usage in the human antibody response to Haemophilus influenzae type b capsular polysaccharide. Adderson, E.E., Shackelford, P.G., Quinn, A., Carroll, W.L. J. Immunol. (1991) [Pubmed]
  19. A strategy for rational design of fully synthetic glycopeptide conjugate vaccines. Chong, P., Chan, N., Kandil, A., Tripet, B., James, O., Yang, Y.P., Shi, S.P., Klein, M. Infect. Immun. (1997) [Pubmed]
  20. Antibiotic-induced bacterial killing stimulates tumor necrosis factor-alpha release in whole blood. Arditi, M., Kabat, W., Yogev, R. J. Infect. Dis. (1993) [Pubmed]
  21. Immunoglobulin variable region gene expression in response to Haemophilus influenzae type b polysaccharide. Carroll, W.L., Adderson, E.E., Quinn, A., Shackelford, P.G. J. Infect. Dis. (1992) [Pubmed]
  22. CD1 presents antigens from a gram-negative bacterium, Haemophilus influenzae type B. Fairhurst, R.M., Wang, C.X., Sieling, P.A., Modlin, R.L., Braun, J. Infect. Immun. (1998) [Pubmed]
  23. Hematogenous bacterial meningitis in an intercellular adhesion molecule-1-deficient infant mouse model. Tan, T.Q., Smith, C.W., Hawkins, E.P., Mason, E.O., Kaplan, S.L. J. Infect. Dis. (1995) [Pubmed]
  24. The effect of interleukin-10 on meningeal inflammation in experimental bacterial meningitis. París, M.M., Hickey, S.M., Trujillo, M., Ahmed, A., Olsen, K., McCracken, G.H. J. Infect. Dis. (1997) [Pubmed]
  25. Genetic factors in Haemophilus influenzae type b disease susceptibility and antibody acquisition. Petersen, G.M., Silimperi, D.R., Rotter, J.I., Terasaki, P.I., Schanfield, M.S., Park, M.S., Ward, J.I. J. Pediatr. (1987) [Pubmed]
  26. Anti-inflammatory properties of human serum IgA: induction of IL-1 receptor antagonist and Fc alpha R (CD89)-mediated down-regulation of tumour necrosis factor-alpha (TNF-alpha) and IL-6 in human monocytes. Wolf, H.M., Hauber, I., Gulle, H., Samstag, A., Fischer, M.B., Ahmad, R.U., Eibl, M.M. Clin. Exp. Immunol. (1996) [Pubmed]
  27. The role of complement in the host's defense against Haemophilus influenzae. Winkelstein, J.A., Moxon, E.R. J. Infect. Dis. (1992) [Pubmed]
  28. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Peltola, H. Clin. Microbiol. Rev. (2000) [Pubmed]
  29. Prevention of Haemophilus influenzae type b infections in Apache and Navajo children. Santosham, M., Rivin, B., Wolff, M., Reid, R., Newcomer, W., Letson, G.W., Almeido-Hill, J., Thompson, C., Siber, G.R. J. Infect. Dis. (1992) [Pubmed]
  30. Antibodies to Haemophilus influenzae type b outer membrane proteins in children with epiglottitis or meningitis and in healthy controls. Johnson, P.D., MacInnes, S.J., Gilbert, G.L. Infect. Immun. (1993) [Pubmed]
  31. Expression of Haemophilus influenzae type b idiotype 1 on naturally acquired antibodies. Ulanova, M., Hahn-Zoric, M., Lau, Y.L., Lucas, A., Hanson, L.A. Clin. Exp. Immunol. (1996) [Pubmed]
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