Viral & Bacterial Infections 2


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Viral & Bacterial Infections 2

  1. 1. VIRAL INFECTION<br />
  2. 2. VIRAL INFECTIONS<br />
  3. 3. Transient Viremia<br />
  4. 4. Measles- Rubeola virus<br /><ul><li>Measles virus is an RNA virus of the paramyxovirus
  5. 5. There is only one strain of measles virus with Envelope</li></li></ul><li>PATHOPHYSIOLOGY<br />
  6. 6. Clinical Manifestation<br />
  7. 7. <ul><li>Antibody-protects against reinfection
  8. 8. T cell-mediated immunity  controls the viral infection  skin rash ( hypersensitivity reaction to viral antigen )
  9. 9. PathognomonicKoplik spots Ulcerated mucosal lesions in the oral cavity near the opening of Stensen ducts
  10. 10. LN  Follicular Hyperplasia & multi- nucleate giant cells, called Warthin-Finkeldey cells, which have eosinophilic nuclear and cytoplasmic inclusion bodies.</li></li></ul><li>Mumps<br /><ul><li>Transient inflammation of the parotid glands and, less often, of the testes, pancreas and central nervous system</li></li></ul><li>
  11. 11. Clinical Manifestation<br /><ul><li>Mumps parotitis, which is bilateral in 70% of cases
  12. 12. Mumps orchitis,  swelling  local hemorrhages  Infarction Sterility due to scars and atrophy of the testis
  13. 13. Pancreasdestructive lesion  causing parenchymal and fat necrosis & pmns
  14. 14. Mumps encephalitis causes perivenousdemyelinization and perivascular mononuclear cuffing.</li></li></ul><li>Poliovirus<br />Unencapsulated RNA virus of Enterovirus<br />Transmitted by fecal-oral route<br />3 major strains <br />Infects people but not other animals<br />Briefly shed <br />Do not undergo antigenic variation<br />EFFECTIVELY PREVENTED BY IMMUNIZATION<br />
  15. 15. Poliovirus<br />
  16. 16. Special Consideration<br />1 : 100 infected invades the CNS<br />Due to VIREMIA or RETROGRADE TRANSPORT VIA AXONS TO MOTOR NEURONS<br />Motor Neurons of Spinal Cord<br />SPINAL POLIOMYELITIS<br />Brain Stem<br />BULBAR POLIOMYELITIS<br />
  17. 17. CHRONIC LATENT INFECTIONS- Herpesvirus infections<br />
  18. 18. Features:<br />Cause Acute Infection  Followed by Latent Infection  <br />Viruses persist in a Non-Infectious Form<br />With Periodic Reactivation & Shedding of Infectious Virus<br />Latency defined<br />Inability to recover Infectious particles from cells that harbor the virus<br />
  19. 19. Herpesvirus infections<br />
  20. 20. Pathophysiology of Latency<br />Viral DNA remains w/in Nucleus of Sensory Neurons<br />No viral protein are produced<br />Only Latency–Associated viral RNA transcripts are synthesized ( LATS )<br />Confer Resistance to Apoptosis<br />Contribute to viral persistence in sensory neurons<br />Reactivation may occur in presence of host immunity<br />Virus Developed ways to avoid Immune Recognition<br />
  21. 21. ESCAPE or Elude Immune System<br />DownModulating MHC class I & II molecules<br />Hide from immune system<br />Producing Homologues of TNF receptor, IL-10 and MHC class I receptors<br />Actively Suppress immune response<br />
  22. 22. Herpes Simplex Virus<br />
  23. 23. Herpesvirus Blister - Mucosa<br />
  24. 24. Herpes Virus<br />
  25. 25. Cytomegalovirus<br />Usually produce Asymptomatic infxn except Immunocompromised<br />Found in All Secretions include Milk<br />Can carry the usual dormant virus for life<br />Transmission<br /> 1. Transplacental 4. Venereal Route<br /> 2. Cervical or Birth Canal 5. Organ transplant <br /> 3. Breast Milk 6. Blood transfusion<br /> 4. Saliva (children-day care) <br />
  26. 26. Diseases:<br />Congenital CMV- acquired in Utero<br />95% asymptomatic<br />Mother w/ primary infection  CID develops<br />Classic cytomegalic inclusion disease CID<br />Similar to erythroblastosisfetalis<br />
  27. 27. Diseases:<br />Perinatal Infections<br />Passage birth canal/breast milk<br />Majority asymptomatic due to ( +) Ig from mother<br />Many continue excrete CMV in urine/saliva x years<br />Pneumonitis Later in life  Hearing loss noted<br />CMV- mononucleosis like illness<br />Fever, atypical lymphos, mild hepatitis, Lymphadenopathy<br />CMV in Immunocompromised<br />Disseminated CMV- lungs, GIT, Retina<br />
  28. 28. Varicella – Zoster Virus<br />Acute Infection – Chickenpox<br />Infects mucous membrane, skin, neurons<br />Reactivation – Herpes zoster / shingles<br />Self-limiting  Latent infxn in Sensory Ganglia<br />Transmitted by Aerosols <br />Disseminates Hematogenously<br />Cause widespread vesicular skin lesions<br />
  29. 29. Varicella-Zoster Virus<br />
  30. 30. Chronic Productive Infections<br />HIV AND HBV<br />
  31. 31. Features of Chronic Productive Infections <br />
  32. 32. Hepatitis B Virus- Hepadna<br />
  33. 33. HBV- Pathogenesis<br />HBV integrate in host genome<br />Cause Hepatic injury is due to immune response not cytopathic effect of virus<br />Cytotoxic T lymphocytes eliminate infected cells<br />Evasion of immune system<br />Inhibiting IFN-beta  downregulation of viral gene expression<br />High mutation rate<br />
  34. 34. HBV- Pathogenesis<br />Chronic Infxn<br />5-10% Adults<br />Up to 90 % Perinatally infected Children<br />Carrier State<br /> Occur when CTL response is Dormant<br />
  35. 35. Transforming Viruses<br />
  36. 36. Transforming infection<br />EBV ,HPV, HBV, HTLV-1<br />
  37. 37. Epstein – Barr Virus<br />
  38. 38. Epstein – Barr Virus<br />
  39. 39. Atypical lymphocytes- Reactive T lymphocytes<br />
  40. 40. Immune Response to EBV<br />
  41. 41. Some<br />Ac quired Defects in Cellular Immunity<br />
  42. 42. Human Papilloma Virus<br />
  43. 43. HPV<br />
  44. 44. Malignant Transformation<br />
  45. 45. Bacterial infection<br />
  46. 46. Gram Positive Bacteria<br />
  47. 47. Staphylococcus aureusInfection<br />Skin Lesions<br />Abscesses<br />Sepsis<br />Osteomyelitis<br />Pneumonia<br />Endocarditis<br />Food Poisoning<br />Toxic Shock Syndrome<br />
  48. 48. Other Staph species<br />Opportunistic infection<br />Prosthetic valves<br />Catheter<br />D rug addicts<br />Polysaccharide capsule – attach artificial materials<br />UTI in young women<br />Staph epidermidis<br />Staph saprophyticus<br />
  49. 49. Pathogenesis- Staph aureus<br />Clumping Factor<br />Binds fibrinogen, Fibronectin, <br />Use as bridge<br />Adhere host Endothelial cells<br />Enzymes - Lipase<br />Degrade skin lipids<br />Protein A <br />Binds the Fc portion of immunoglobulins – Escape Ab-mediated killing<br />
  50. 50. Pathogenesis- Staph aureus<br />Superantigens<br />Stimulate 2 0 % of Lymphos Release of large amounts of TNF, IL-1  Septic Shock<br />Toxins –Damage host cell<br />Membrane damaging toxins<br />
  51. 51. Exfoliative Toxins<br />
  52. 52. staph food poisoning <br />
  53. 53. Diseases Causesd by Staphy.<br />
  54. 54. Streptococcal infection<br />
  55. 55. Beta Hemolytic Strep <br />
  56. 56. Strep Pharingitis<br />Epiglottal swelling & abscess<br />Cervical LN<br />Strep Pyogenes<br />Major antecedent of PoststrepGlomerulonephritis<br />Ag-Ab complex deposit in glomerulus<br />Poststrep Rheumatic fever<br />Antistreptococcal M protein antibodies & T cells that cross react with cardiac myosin<br />
  57. 57. Strep pyogenes:VirulenceFactors<br />Capsules <br />M proteins – prevents phagocytosis<br />C5a peptidase – Degrade chemotactic C5<br />Antistreptococcal M protein – Ab that cross react w/ cardiac Myosin ( RHD)<br />
  58. 58. Other Streptococcal Infection<br />Strep. Pneumoniae<br />Common cause of CAP & Adult Meningitis <br />Lobar Pneumonia<br />Otitis media, Sinusitis<br />Often preceded by viral infection that injure ciliated epithelium<br />Has capsule- prevent phagocytosis<br />Pneumolysin<br />Inserts on target cell membrane  Lysis<br />Activates Classical pathway Reducing complement available for Opsinization<br />
  59. 59. Beta Hemolytic Strep <br />
  60. 60. Other Streptococcal Infection<br />Strep. Mutans<br />Major cause of Dental Caries<br />Sucrose  Lactic acid  Demineralization of Tooth enamel<br />Secrete HMW Glucans Promote Bacterial Aggregation  Plaque formation<br />
  61. 61. Gram negative bacteria<br />Salmonella<br />Neisserialinfxn<br />Whooping cough<br />Pseudomonas<br />Chancroid<br />Granulomainguinale<br />
  62. 62. Salmonella Typhi<br />Enteric fever<br />Transmitted <br />From person to person<br />Food or Contaminated water<br />GB colonization may be associated with<br />Gallstones<br />Chronic Carrier State<br />
  63. 63. Pathogenesis<br />Survive gastric acid<br />In the SI  Taken by M cells<br /> Engulf by macrophages in the underlying LN Reactive LN hyperplasia<br />Disseminate by blood & Lymphatic<br />Unlike S. enteriditidis<br />
  64. 64. Clinical manifestation of Typhoid Fever<br />
  65. 65. Pathogenesis- Salmonella<br />
  66. 66. Typhoid fever<br />Blood Culture<br />&gt;90% in the Febrile State<br />Relapse may occur<br />Systemic dissemination <br />Encephalopathy <br />Meningitis<br />Seizures<br />Endocarditis<br />Myocarditis<br />Pneumonia<br />Cholecystitis<br />Osteomyeltis<br />
  67. 67. Neisseria Infections<br />2 Clinically significant species<br />N. meningitidis<br />N. gonorrhea<br />
  68. 68. Neisseriameningitidis<br />13 serotypes<br /><ul><li>Common Colonizes Oropharynx
  69. 69. Spread by respiratory route</li></ul>Only small fraction develop Cause Bacterial Meningitis<br />Children less than 2 years old<br />
  70. 70. Pathophysiology- N. meningitidis - <br />
  71. 71. Neisseria gonorrhea<br />Surface pili that form barrier against phagocytosis<br />Encapsulated gm(-) diplococci<br />STI – Men - Urethritis, Pharyngitis, Proctitis<br />Urethral strictures, chronic infection of Male genitals<br />STI – Women - Salpingitis Tubo-ovarian abscess  Scar  Sterility or Ectopic pregnancy<br />Perinatal Ophthalmic infxn<br />
  72. 72. Neisseria gonorrhea<br />
  73. 73. Neisseria - Evasion of immune response<br />Use antigenic variation of OPA proteins to escape immune response<br />A single clone of bacteria  several multiple antigenic types<br />Pili Protein are altered by genetic recombination<br />
  74. 74. Whooping cough<br />Gram (-) coccobacilli<br />Acute highly communicable <br />Paroxysm of violent cough followed by loud inspiratory whoop<br />Colonizes the brush border of bronchial epithelium<br />Laryngotracheobronchitis<br />Virulence is regulated by BVG locus<br />
  75. 75. Virulence factor :Regulated by Bordetella virulence gene locus (bvg)<br />PertusisExotoxins paralyze cilia<br />
  76. 76. Pseudomonas Infection<br /> Opportunistic gram-negative bacterium <br />Frequent, deadly pathogen of patients with cystic fibrosis, severe burns, or neutropenia. <br />Coregulatedpili<br />Adherence proteins that mediate adherence to epithelial cells and lung mucin<br />Endotoxinthat causes the symptoms and signs of gram-negative sepsis.<br />
  77. 77. Distinctive Virulence Factor<br />
  78. 78. Distinctive Virulence Factor<br />
  79. 79. Distinctive Virulence Factor<br />
  80. 80. Syphilis- Treponemapallidum<br />Sexual intercourse is the usual mode of transmission<br />Transplacental transmission of T. pallidum occurs readily, & active disease during pregnancy results in congenital syphilis.<br />
  81. 81. Pathology - syphilis<br />
  82. 82. Chancre<br />Sensored<br />A single firm, nontender, raised, red lesion<br />3 weeks after contact<br />Heals in a few weeks with or without therapy<br />
  83. 83.
  84. 84.
  85. 85. Immune response to Syphlis<br />
  86. 86. Pathogenesis of Syphilis<br />
  87. 87. Obliterative endarteritis<br />
  88. 88. Anaerobic Bacteria<br />Clostridia Infection<br />
  89. 89. Clostridial Infections<br />Clostridium species are gram-positive bacilli<br />There are four types of Clostridium that cause human disease: <br />1.Clostridium perfringens (welchii), septicum<br />2.Clostridium tetani<br />3.Clostridium botulinum<br />4.Costridium difficile<br />
  90. 90. Clostridium perfringens (welchii)<br />Anaerobic cellulitis – foul , thin discolored exudate, quick tissue destruction ( versus pyogenic )<br />Myonecrosis (gas gangrene)- 1to 3 days after infection<br />Invade traumatic and surgical wounds <br />Contaminate illegal abortions <br /> Cause uterine myonecrosis, <br /> Cause mild food poisoning, <br /> Infect the small bowel of ischemic or neutropenic patients to produce severe sepsis.<br />
  91. 91. Clostridium tetani<br />Proliferates in:<br /> puncture wounds <br />umbilical stump of newborn infants <br /> Releases a potent neurotoxin, called tetanospasmin<br /> causes convulsive contractions of skeletal muscles (lockjaw).<br />
  92. 92. Clostridium botulinum<br />Grows in inadequately sterilized canned foods <br />Releases a potent neurotoxin that blocks synaptic release of acetylcholine <br />Causes a severe paralysis of respiratory and skeletal muscles (botulism).<br />
  93. 93. Clostridium difficile<br />Overgrows other intestinal flora in antibiotic-treated patients<br />Releases multiple toxin<br />Causes pseudomembranous colitis <br />
  94. 94. Pathogenesis- Clostridium Perfringens<br />
  95. 95. Alpha Toxin- Properties<br />
  96. 96. Beta toxin<br />
  97. 97. O Toxins<br />
  98. 98. Clostridium tetani<br />
  99. 99. Clostridium Botulinum- Neurotoxin<br />Are released when the organisms die and autolyse<br />Act at the peripheral nerve endings, <br />Cleaving either synaptobrevin (as described for tetanus toxin) or synapse-associated proteins, called SNAP-25 and syntaxin.<br />
  100. 100. Unable to release acetylcholine at the neuromuscular junction and at the synaptic ganglia and parasympathetic motor end-plates of the autonomic nervous system<br />Descending paralysis from the cranial nerves down to the extremities.<br />
  101. 101. Clostridium difficile<br />Produces toxin A<br />Which is an enterotoxin<br />a potent chemoattractant for granulocytes<br /> toxin B<br />a cytotoxin, <br />which causes distinctive cytopathic effects in cultured cells and is used in the diagnosis of C. difficile infections<br />
  102. 102. Obligate Intracellular Bacteria<br />Chlamydia trachomatis is an obligate intracellular pathogen<br />Venereal urethritis, lymphogranulomavenereum, and trachoma<br />Lymphogranulomavenereum<br /> results in granulomatous inflammation of the inguinal and rectal lymph nodes. <br />Trachoma or chronic keratoconjunctivitis, a leading global cause of blindness, is a disease of poverty and overcrowding, transmitted from eye to eye by aerosols or by hand contact.<br />
  103. 103. Malaria<br />Intracellular protozoan parasite <br />Plasmodium falciparum is a worldwide infection that affects 100 million and kills 1 to 1.5 million persons per year and so is the major parasitic cause of death. <br />Other types (P. vivax, P. ovale, P. malariae)<br />Transmitted by more than a dozen species of Anopheles mosquitoes widely distributed throughout Africa, Asia, and Latin America. <br />
  104. 104. Malaria<br />P. vivax and P. malariae<br /> mild anemia <br />in rare instances, splenic rupture and nephrotic syndrome. <br />Acute P. falciparum infections<br />produce high parasitemias, <br />severe anemia, <br />cerebral symptoms, <br />renal failure, <br />pulmonary edema, and death. <br />
  105. 105. Features of P. falciparum<br />Infect rbc of all ages Versus young rbc for other species<br />High parasite burden <br />Profound Anemia<br />Infected rbc clump together  Stick to Endothelial lining of small blood vessels ( Sequestration )  Block blood flow <br />Form KNOBs on rbc surface (PfEMP 1)<br />Plasmodium falc. Eryhtrocytememb protein <br />Bind Ligands on blood vessel wall<br />Cause poor perfusion to the brain ( Cerebral malaria )<br />
  106. 106. Life cycle of P. falciparum<br />
  107. 107. Features of P. falciparum<br />Stimulates production of HIGH levels of Cytokines<br />Induce fever<br />Suppress rbc production<br />NO prodn Tissue damage<br />Induce expression of endothelial receptors for PfEMP 1 <br />Increasing sequestration<br />
  108. 108. Morphology<br />P. falciparum initially  Splenic congestion and enlargement of the spleen <br />Infected rbc taken byreticuloendothelial cells.<br />The liver becomes progressively enlarged and pigmented with progression of malaria. <br />Kidneys  often enlarged and congested <br /> pigment in the glomeruli and hemoglobin <br /> casts in the tubules.<br />
  109. 109. Addendum<br />Sporozoites – Infectious stage<br />During feeding SporozoitesReleased in blood w/in minutes Bind to and invade liver cells<br /> by binding to the hepatocyte receptor for the serum proteins thrombospondin and properdin, located on the basolateral surface of hepatocytes<br />The binding is accomplished because of the presence of sporozoite surface proteins that contain a domain homologous to the binding domain of thrombospondin. <br />Within liver cells, malaria parasites multiply rapidly, so as many as 30,000 merozoites (asexual, haploid blood forms) <br />Merozoites released when the hepatocyte ruptures<br />
  110. 110. Addendum<br />Merozoites bind by a parasite lectin-like molecule to sialic residues on glycophorin molecules on the surface of red blood cells. <br />Merozoitesrelease multiple proteases from a special organelle called the rhoptry.<br />Within the red blood cells, the parasites multiply in a membrane-bound digestive vacuole,<br />Hydrolyzing hemoglobin through secreted enzymes that include an aspartate protease<br />Most malaria parasites  rupture the cell  infect new red blood cells<br />Some parasites sexual forms called gametocytes  infect the mosquito when it takes its blood meal.<br />
  111. 111. Addendum<br />Maturation  change morphologic  from ring to schizont form  secrete proteins that form 100-nm bumps on the red blood cell surface, called knobs called sequestrins<br />Sequestrins bind to endothelial cells by ICAM-1, the thrombospondin receptor, and the glycophorin CD46 <br />cause malaria-infected red blood cells to be removed from circulation<br />Red blood cells containing immature ring forms of the parasite  flexible  pass through the spleen, circulate in the blood<br />Red blood cells containing mature schizonts, <br /> rigid  sequestration in the spleen. <br />
  112. 112. Schistosoma<br />
  113. 113. Schistosoma<br />S. mansoni / japonicum eggs  liver disease.<br />1. Substances released from schistosome eggs <br />Are directly hepatotoxic, <br />2. Carbohydrate antigens from eggs induce Granuloma formation<br /> mediated by TNF and TH 1 and TH 2 helper cells.<br /> TH 2 helper T cells  secrete IL-4 Induce IgE synthesis eosinophilia, mastocytosis, and high levels of serum IgE in human schistosomiasis<br />Resistance to reinfection by schistosomes after treatment correlates with IgE levels<br />Whereas eosinophil major basic protein may destroy larval schistosomula<br />
  114. 114. 3. Eggs release factors that stimulate lymphocytes secrete a fibrogeniclymphokine<br />Stimulates fibroblast proliferation and portal fibrosis. <br />This exuberant periportal fibrosis, which is out of proportion to the injury caused by the eggs and granulomas, <br />Pipestem Fibrosis<br />Occurs in 5% - 10% of persons heavuly infected with schistosomes<br /> Hallmarks of severe schistosomiasis:<br />Portal hypertension <br />Esophageal varices, <br />Ascites<br />
  115. 115. Pipestem Fibrosis - Liver<br />
  116. 116. S. haematobium infection,<br />Bladder inflammatory patches due to massive egg deposition and granulomas<br />cause hematuria<br />The most frequent complication is inflammation and fibrosis of the ureteral walls<br /> leading to obstruction, hydronephrosis, and chronic pyelonephritis. <br />
  117. 117. Schisoma eggs<br />