Chapter 20 : Pathology and Pathogenesis of Bacterial Infections

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This chapter provides a classification of relevant immunopathological reactions depending on the underlying mechanisms leading to tissue damage. The release of mediators such as histamine, leukotrienes, and heparin from mast cells accounts for the anaphylactic reactions to horse serum or to penicillin but is usually not important in the immunopathology of bacterial infections. CD8 T cells may contribute to host resistance by at least four mechanisms: (i) release of IFN-γ, (ii) lysis of the target cell, (iii) induction of apoptosis of the target cells, and (iv) mediation of direct antimicrobial activity. This chapter provides a brief outline of the immunoprotective and immunopathological features of these mechanisms, using tuberculosis as an example. Cytokines therefore play an important role in immune defense but also contribute to immunopathology and disease. Although tumor necrosis factor (TNF) is crucial to the protective immune response, it also plays a part in the immunopathology of tuberculosis. The typical clinical syndrome, in conjunction with knowledge about the pathophysiology of septic shock, has supported the hypothesis that TNF is released at the onset of antimycobacterial therapy and mediates immunopathology. Mechanistically, one could argue that harmful effects may be ascribed to the biological activity of TNF in affecting vascular endothelium by inducing procoagulant activity, formation of thrombi, and production of nitric oxide synthase, thus causing endarteritis. Rheumatic fever is the most commonly cited example of molecular mimicry in humans.

Citation: Stenger S, Modlin R. 2002. Pathology and Pathogenesis of Bacterial Infections, p 281-292. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch20
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1. Altman, E. M.,, L. V. Centeno,, M. Mahal,, and L. Bielory. 1994. AIDS-associated Reiter’s syndrome. Ann. Allergy 72: 307 316.
2. Ando, M.,, M. Suga,, and H. Kohrogi. 1999. A new look at hypersensitivity pneumonitis. Curr. Opin. Pulm. Med. 5: 299 304.
3. Barnett, L. A.,, and M. W. Cunningham. 1992. Evidence for actin-like proteins in an M protein-negative strain of Streptococcus pyogenes. Infect. Immun. 60: 3932 3936.
4. Bean, A. G.,, D. R. Roach,, H. Briscoe,, M. P. France,, H. Körner,, J. D. Sedgwick,, and W. J. Britton. 1999. Structural deficiencies in granuloma formation in TNF-gene targeted mice underlie the hightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin. J. Immunol. 162: 3504 3511.
5. Bekker, L. G.,, G. Maartens,, L. Steyn,, and G. Kaplan. 1998. Selective increase in plasma tumor necrosis factor alpha and concomitant clinical deterioration after initiating therapy in patients with severe tuberculosis. J. Infect. Dis. 178: 580 584.
6. Bessen, D.,, K. F. Jones,, and V. A. Fischetti. 1989. Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever. J. Exp. Med. 169: 269 283.
7. Borsellino, G.,, O. Koul,, R. Placido,, D. Tramonti,, S. Lucchetti,, S. Galgani,, M. Salvetti,, C. Gasperini,, G. Ristori,, B. Bonetti,, S. Bach,, B. Cipriani,, and L. Battistini. 2000. Evidence for a role of gammadelta T cells in demyelinating diseases as determined by activation states and responses to lipid antigens. J. Neuroimmunol. 107: 124 129.
8. Cheadle, W. B. 1889. Harveian lectures on the various manifestations of the rheumatic disease state as exemplified in childhood and early life. Lancet i: 821 827.
9. Claudy, A. 1998. Pathogenesis of leukocytoclastic vasculitis. Eur. J. Dermatol. 8: 75 79.
10. Coombs, R. R. A.,, and P. G. H. Gell,. 1963. The classification of allergic reactions underlying disease, p. 317 337. In P. G. H. Gell, and R. R. A. Coombs (ed.), Clinical Aspects of Immunology. Blackwell Scientific Publications, Oxford, United Kingdom.
11. Cooper, A. M.,, D. K. Dalton,, T. A. Stewart,, J. P. Griffin,, D. G. Russell,, and I. M. Orme. 1993. Disseminated tuberculosis in interferon-gamma gene-disrupted mice. J. Exp. Med. 178: 2243 2247.
12. Cooper, A. M.,, C. D’Souza,, A. A. Frank,, and I. M. Orme. 1997. The course of Mycobacterium tuberculosis infection in the lungs of mice lacking expression of either perforin- or granzyme-mediated cytolytic mechanisms. Infect. Immun. 65: 1317 1320.
13. Cooper, N. R., 1999. Biology of the complement system, p. 281 315. In D. T. Fearon,, B. F. Haynes,, >C. Nathan,, J. G. Gallin,, and R. Snyderman (ed.), Inflammation. Basic Principles and Clinical Correlates, 3rd ed. Lippincott Williams&Wilkins, Philadelphia, Pa.
14. Cribier, B.,, A. Caille,, E. Heid,, and E. Grosshans. 1998. Erythema nodosum and associated diseases. A study of 129 cases. Int. J. Dermatol. 37: 667 672.
15. Cunningham, M. W., 1996. Streptococci and rheumatic fever, p. 13 66. In H. N. Friedman,, R. Rose,, and M. Bendinelli (ed.), Microorganisms and Autoimmune Disease. Plenum Press, New York, N.Y.
16. Cunningham, M. W.,, J. M. McCormack,, L. R. Talaber,, J. B. Harley,, E. M. Ayoub,, R. S. Muneer,, L. T. Chun,, and D. V. Reddy. 1988. Human monoclonal antibodies reactive with antigens of the group A Streptococcus and human heart. J. Immunol. 141: 2760 2766.
17. Dalton, D. K.,, S. Pitts-Meek,, S. Keshav,, I. S. Figari,, A. Bradley,, and T. A. Stewart. 1993. Multiple defects of immune cell function in mice with disrupted interferon gamma genes. Science 259: 1739 1742.
18. Dannenberg, A. M., Jr.,, and G. A. W. Rook,. 1994. Pathogenesis of pulmonary tuberculosis: an interplay of tissue damaging and macrophage-activating immune responses—dual mechanisms that control bacillary multiplication, p. 459 483. In B. R. Bloom (ed.), Tuberculosis: Pathogenesis, Protection and Control. American Society for Microbiology, Washington, D.C.
19. de Libero, G.,, I. Flesch,, and S. H. E. Kaufmann. 1988. Mycobacteria- reactive Lyt-2+ T cell lines. Eur. J. Immunol. 18: 59 66.
20. Feizi, T. 1967. Cold agglutinins, the direct Coomb’s test and serum immunoglobulins in Mycoplasma pneumoniae infection. Ann. N. Y. Acad. Sci. 143: 801 812.
21. Fenton, M. J.,, and M. W. Vermeulen. 1996. Immunopathology of tuberculosis: roles of macrophages and monocytes. Infect. Immun. 64: 683 690.
22. Finne, J.,, M. Leinonen,, and P. H. Makela. 1983. Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet ii: 355 357.
23. Flynn, J. L.,, M. M. Goldstein,, J. Chan,, K. J. Triebold,, K. Pfeffer,, C. J. Lowenstein,, R. Schreiber,, T. W. Mak,, and B. R. Bloom. 1995. Tumor necrosis factor alpha is required for the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2: 561 572.
24. Flynn, J. L.,, M. M. Goldstein,, K. J. Triebold,, B. Koller,, and B. R. Bloom. 1992. Major histocompatibility complex class I restricted T cells are required for resistence to Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA 89: 12013 12017.
25. Gazzinelli, R. T.,, F. T. Hakim,, S. Hieny,, G. M. Shearer,, and A. Sher. 1991. Synergistic role of CD4+ and CD8+ T-lymphocytes in IFN gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J. Immunol. 146: 286 292.
26. Gerard, H. C.,, P. J. Branigan,, T. Arayssi,, J. H. Klippel,, H. R. Schumacher,, and A. P. Hudson. 1998. Synovial Chlamydia trachomatis in patients with reactive arthritis / Reiter’s syndrome are viable but show aberrant gene expression. J. Rheumatol. 24: 1092 1100.
27. Goodyear, C. S.,, G. M. O’Hanlon,, J. J. Plomp,, E. R. Wagner,, I. Morrison,, J. Veitch,, L. Cochrane,, R. W. Bullens,, P. C. Molenaar,, J. Conner,, and H. J. Willison. 1999. Monoclonal antibodies raised against Guillain-Barre syndrome-associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations. J. Clin. Investig. 104: 697 708.
28. Green, D. G.,, and C. F. Ware. 1997. Fas-ligand: privilege and peril. Proc. Natl. Acad. Sci. USA 94: 5986 5990.
29. Guilherme, L.,, E. Cunha-Neto,, V. Coelho,, R. Snitcowsky,, P. M. Pomerantzeff,, R. V. Assis,, F. Pedra,, J. Neumann,, A. Goldberg,, M. E. Pattaroyo,, F. Pileggi,, and J. Kalil. 1995. Human heart-infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins. Circulation 92: 415 420.
30. Guilherme, L.,, N. Dulphy,, C. Douay,, V. Coelho,, E. Cunha-Neto,, S. E. Oshiro,, R. V. Assis,, A. C. Tanaka,, P. M. Alberto Pomerantzeff,, D. Charron,, A. Toubert,, and J. Kalil. 2000. Molecular evidence for antigen-driven immune responses in cardiac lesions of rheumatic heart disease patients. Int. Immunol. 12: 1063 1074.
31. Gulizia, J. M.,, M. W. Cunningham,, and B. M. McManus. 1991. Immunoreactivity of anti-streptococcal monoclonal antibodies to human heart valves. Evidence for multiple cross-reactive epitopes. Am. J. Pathol. 138: 285 301.
32. Hao, Q.,, T. Saida,, S. Kuroki,, M. Nishimura,, M. Nukina,, H. Obayashi,, and K. Saida. 1998. Antibodies to gangliosides and galactocerebroside in patients with Guillain-Barre syndrome with preceding Campylobacter jejuni and other identified infections. J. Neuroimmunol. 81: 116 126.
33. Haslett, P. A.,, L. G. Corral,, M. Albert,, and G. Kaplan. 1998. Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+V subset. J. Exp. Med. 187: 1885 1892.
34. Hemmer, B.,, B. Gran,, Y. Zhao,, A. Marques,, J. Pascal,, A. Tzou,, T. Kondo,, I. Cortese,, B. Bielekova,, S. E. Straus,, H. F. Mc- Farland,, R. Houghton,, R. Simon,, C. Pinilla,, and R. Martin. 1999. Identification of candidate T cell epitopes and molecular mimics in chronic Lyme disease. Nat. Med. 5: 1375 1382.
35. Hirsch, C. S.,, J. J. Ellner,, D. G. Russell,, and E. A. Rich. 1994. Complement receptor-mediated uptake and tumor necrosis factor alpha-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. J. Immunol. 152: 743 753.
36. Horwitz, C. A.,, J. Moulds,, W. Henle,, G. Henle,, H. Polesky,, H. H. Balfour, Jr.,, B. Schwartz,, and T. Hoff. 1977. Cold agglutinins in infectious mononucleosis and heterophil-antibody-negative mononucleosis-like syndromes. Blood 50: 195 202.
37. Huber, M.,, E. Timms,, T. W. Mak,, M. Röllinghoff,, and M. Lohoff. 1998. Effective and longlasting immunity against the parasite Leishmania major in CD8-deficient mice. Infect. Immun. 66: 3968 3970.
38. Jouanguy, E.,, F. Altare,, S. Lamhamedi,, P. Revy,, J. Emile,, M. Newport,, M. Levin,, S. Blanche,, E. Seboun,, A. Fischer,, and J. Casanova. 1996. Interferon-gamma receptor deficiency in an infant with fatal bacille Calmette Guerin infection. N. Engl. J. Med. 335: 1956 1961.
39. Kaplan, M. H.,, and M. Meyeserian. 1962. An immunological cross-reaction between group A streptococcal cells and human heart tissue. Lancet i: 706 710.
40. Kaufmann, S. H. E. 1988. CD8+ T lymphocytes in intracellular microbial infections. Immunol. Today 9: 168 174.
41. Khalili-Shirazi, A.,, R. A. Hughes,, S. W. Brostoff,, C. Linington,, and N. Gregson. 1992. T cell responses to myelin proteins in Guillain-Barre syndrome. J. Neurol. Sci. 111: 200 203.
42. Kindler, V.,, A. P. Sappino,, G. E. Grau,, P. F. Piguet,, and P. Vassalli. 1989. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56: 731 740.
43. Klempner, M. S.,, and B. T. Huber. 1999. Is it thee or me? Autoimmunity in Lyme disease. Nat. Med. 5: 1346 1347.
44. Ladel, C. H.,, I. E. Flesch,, J. Arnoldi,, and S. H. E. Kaufmann. 1994. Studies with MHC-deficient knock out mice reveal impact of both MHC-I and MHC-II-dependent T cell responses on Listeria monocytogenes infection. J. Immunol. 153: 3116 3122.
45. Laochumroonvorapong, P. J. Wang, C. C. Liu, W. Ye, A. L. Moreira, K. B. Elkon, V. H. Freedman, and G. Kaplan. 1997. Perforin, a cytotoxic molecule which mediates cell necrosis, is not required for the early control of mycobacterial infection in mice. Infect. Immun. 65: 127 132.
46. Levinsky, R. J.,, and T. M. Barratt. 1979. IgA immune complexes in Henoch-Schoenlein purpura. Lancet. ii: 1100 1103.
47. Levitz, S. M.,, H. L. Mathews,, and J. W. Murphy. 1995. Direct antimicrobial activity of T cells. Immunol. Today 16: 387 391.
48. Liles, W. C. 1997. Apoptosis: role in infection and inflammation. Curr. Opin. Infect. Dis. 10: 165 170.
49. Limpanasithikul, W.,, S. Ray,, and B. Diamond. 1995. Cross-reactive antibodies have both protective and pathogenic potential. J. Immunol. 155: 967 973.
50. Loomes, L. M.,, K. Uemura,, R. A. Childs,, J. C. Paulson,, G. N. Rogers,, P. R. Scudder,, J. C. Michalski,, E. F. Hounsell,, D. Taylor-Robinson,, and T. Feizi. 1984. Erythrocyte receptors for Mycoplasma pneumoniae are sialylated oligosaccharides of Ii antigen type. Nature 307: 560 563.
51. Magro, C. M.,, and A. N. Crawson. 1999. A clinical and histological study of 37 cases of IgA associated vasculitis. Am. J. Dermatopathol. 21: 234 240.
52. Moe, G. R.,, S. Tan,, and D. M. Granhoff. 1999. Molecular mimetics of polysaccharide epitopes as vaccine candidates for prevention of Neisseria meningitidis serogroup B disease. FEMS Immunol. Med. Microbiol. 26: 209 226.
53. Mygind, N.,, R. Dahl,, S. Pedersen,, and K. Thestrup-Pedersen,. 1996. Other allergic lung diseases, p. 400 408. In N. Mygind,, R. Dahl,, S. Pedersen,, and K. Thestrup-Pedersen (ed.), Essential Allergy, 2nd ed. Blackwell Science, Cambridge, Mass.
54. Newport, M. J.,, C. M. Huxley,, S. Huston,, C. M. Hawrylowicz,, B. A. Oostra,, R. Williamson,, and M. Levin. 1996. A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. N. Engl. J. Med. 335: 1941 1949.
55. Nikkari, S.,, R. Merilahti,, R. Saario,, K. O. Soderstrom,, K. Granfors,, M. Skurnik,, and P. Toivanen. 1992. Yersinia-triggered reactive arthritis: use of polymerase chain reaction and immunocytochemical staining in the detection of bacterial components from synovial specimens. Arthritis Rheum. 35: 682 687.
56. Nordstrand, A.,, M. Norgren,, and S. E. Holm. 1999. Pathogenic mechanisms of acute post-streptococcal glomerulonephritis. Scand. J. Infect. Dis. 31: 523 537.
57. Olivier, C. 2000. Rheumatic fever—is it still a problem? J. Antimocrob. Ther. 45: 13 21.
58. Pena, S. V.,, D. A. Hanson,, B. A. Carr,, T. J. Goralski,, and A. M. Krensky. 1997. Processing, subcellular localization, and function of 519 (granulysin), a human late T cell activation molecule with homology to small, lytic, granule proteins. J. Immunol. 158: 2680 2688.
59. Ray, S. K.,, C. Putterman,, and B. Diamond. 1996. Pathogenic autoantibodies are routinely generated during the response to foreign antigen: a paradigm for autoimmune disease. Proc. Natl. Acad. Sci. USA 93: 2019 2024.
60. Rook, G. A. W.,, and B. R. Bloom,. 1994. Mechanisms of pathogenesis in tuberculosis,, p. 485 501. In B. R. Bloom (ed.), Tuberculosis: Pathogenesis, Protection, and Control. American Society for Microbiology, Washington, D.C.
61. Rook, G. A. W.,, and J. L. Stanford,. 1996. The Koch phenomenon and the immunopathology of tuberculosis, p. 239 262. In T. M. Shinick (ed.), Tuberculosis. Springer-Verlag KG, Berlin, Germany.
62. Rottenberg, M. E.,, M. Bakhiet,, T. Olsson,, K. Kristensson,, T. Mak,, H. Wigzell,, and A. Orn. 1993. Differential susceptibilities of mice genomically deleted of CD4 and CD8 to infections with Trypanosoma cruzi and Trypanosoma brucei. Infect. Immun. 61: 5129 5133.
63. Sampaio, E. P.,, E. N. Sarno,, R. Galilly,, Z. A. Cohn,, and G. Kaplan. 1991. Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J. Exp. Med. 173: 699 703.
64. Santucci, M. B.,, M. Amicosante,, R. Cicconi,, C. Montesano,, M. Casarini,, S. Giosue,, A. Bisetti,, and M. Fraziano. 2000. Mycobacterium tuberculosis-induced apoptosis in monocytes/ macrophages: early membrane modifications and intracellular mycobacterial viability. J. Infect. Dis. 181: 1506 1509.
65. Schluger, N. W.,, and W. N. Rom. 1998. The host immune response to tuberculosis. Am. J. Respir. Crit. Care Med. 157: 679 691.
66. Sell, S. 1987. Immunology, Immunopathology and Immunity, 4th ed., p. 373 412. Elsevier Science Publishing Co., New York, N.Y..
67. Sharma, O. P.,, and R. Chwogule. 1998. Many faces of pulmonary aspergillosis. Eur. Respir. J. 12: 705 715.
68. Slifka, M. K.,, F. Rodriguez,, and J. L. Whitton. 1999. Rapid on/ off cycling of cytokine production by virus-specific CD8+ T cells. Nature 401: 76 79.
69. Slifka, M. K.,, and J. L. Whitton. 2000. Antigen-specific regulation of T cell-mediated cytokine production. Immunity 12: 451 457.
70. Steinhoff, U.,, V. Brinkmann,, U. Klemm,, P. Aichele,, P. Seiler,, U. Brandt,, P. W. Bland,, I. Prinz,, U. Zügel,, and S. H. Kaufmann. 1999. Autoimmune intestinal pathology induced by hsp60- specific CD8 T cells. Immunity 11: 349 358.
71. Stenger, S.,, D. A. Hanson,, R. Teitelbaum,, P. Dewan,, K. R. Niazi,, C. J. Froelich,, T. Ganz,, S. Thoma-Uszynski,, A. Melian,, C. Bogdan,, S. A. Porcelli,, B. R. Bloom,, A. M. Krensky,, and R. L. Modlin. 1997. An antimicrobial activity of cytolytic T-cells mediated by granulysin. Science 282: 121 125.
72. Stenger, S.,, R. J. Mazzaccaro,, K. Uyemura,, S. Cho,, P. F. Barnes,, J. P. Rosat,, A. Sette,, M. B. Brenner,, S. A. Porcelli,, B. R. Bloom,, and R. L. Modlin. 1997. Differential effects of cytolytic T cell subsets on intracellular infection. Science 276: 1684 1687.
73. Stenger, S.,, and R. Modlin. 1998. Cytotoxic T cell responses to intracellular pathogens. Curr. Opin. Immunol. 10: 471 477.
74. Tramontana, J. M.,, U. Utaipat,, A. Molloy,, P. Akarasewi,, M. Burroughs,, S. Makonkawkeyoon,, B. Johnson,, J. D. Klausner,, W. Rom,, and G. Kaplan. 1995. Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis. Mol. Med. 1: 384 387.
75. Tsenova, L.,, A. Bergtold,, V. H. Freedman,, R. A. Young,, and G. Kaplan. 1999. Tumor necrosis factor alpha is a determinant of pathogenesis and disease progression in mycobacterial infection in the central nervous system. Proc. Natl. Acad. Sci. USA 96: 5657 1662.
76. Vedeler, C. A. 2000. Inflammatory neuropathies: update. Curr. Opin. Neurol. 13: 305 309.
77. Wang, Z.-E.,, S. L. Reiner,, F. Hatam,, F. P. Heinzel,, J. Bouvier,, C. W. Turck,, and R. M. Locksley. 1993. Targeted activation of CD8+ cells and infection of β2-microglobulin-deficient mice fail to confirm a protective role for CD8 cells in experimental leishmaniasis. J. Immunol. 151: 2077 2086.
78. Yuki, N.,, T. Taki,, F. Inagaki,, T. Kasama,, M. Takahashi,, K. Saito,, S. Handa,, and T. Miyatake. 1993. A bacterium lipopolysaccharide that elicits Guillain-Barre syndrome has a GM1 ganglioside-like structure. J. Exp. Med. 178: 1771 1775.
79. Zabriskie, J. B. 1971. The role of streptococci in human glomerulonephritis. J. Exp. Med. 134(Suppl.): 180S.

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