This document summarizes several viral, bacterial, and parasitic infections. It describes measles, mumps, poliovirus, herpes viruses, hepatitis B, Epstein-Barr virus, human papillomavirus, bacterial infections including Staphylococcus aureus, Streptococcus, Salmonella, Neisseria, Bordetella, Clostridium, malaria and more. Key details are provided on pathogenesis, clinical manifestations, virulence factors that help pathogens evade the immune system, and mechanisms of latent or chronic infections.

1. VIRAL INFECTION

2. VIRAL INFECTIONS

3. Transient Viremia

6. Clinical Manifestation

8. T cell-mediated immunity  controls the viral infection  skin rash ( hypersensitivity reaction to viral antigen )

9. PathognomonicKoplik spots Ulcerated mucosal lesions in the oral cavity near the opening of Stensen ducts

12. Mumps orchitis,  swelling  local hemorrhages  Infarction Sterility due to scars and atrophy of the testis

13. Pancreasdestructive lesion  causing parenchymal and fat necrosis & pmns

15. Poliovirus

16. Special Consideration 1 : 100 infected invades the CNS Due to VIREMIA or RETROGRADE TRANSPORT VIA AXONS TO MOTOR NEURONS Motor Neurons of Spinal Cord SPINAL POLIOMYELITIS Brain Stem BULBAR POLIOMYELITIS

17. CHRONIC LATENT INFECTIONS- Herpesvirus infections

18. Features: Cause Acute Infection  Followed by Latent Infection  Viruses persist in a Non-Infectious Form With Periodic Reactivation & Shedding of Infectious Virus Latency defined Inability to recover Infectious particles from cells that harbor the virus

19. Herpesvirus infections

20. Pathophysiology of Latency Viral DNA remains w/in Nucleus of Sensory Neurons No viral protein are produced Only Latency–Associated viral RNA transcripts are synthesized ( LATS ) Confer Resistance to Apoptosis Contribute to viral persistence in sensory neurons Reactivation may occur in presence of host immunity Virus Developed ways to avoid Immune Recognition

21. ESCAPE or Elude Immune System DownModulating MHC class I & II molecules Hide from immune system Producing Homologues of TNF receptor, IL-10 and MHC class I receptors Actively Suppress immune response

22. Herpes Simplex Virus

23. Herpesvirus Blister - Mucosa

24. Herpes Virus

25. Cytomegalovirus Usually produce Asymptomatic infxn except Immunocompromised Found in All Secretions include Milk Can carry the usual dormant virus for life Transmission 1. Transplacental 4. Venereal Route 2. Cervical or Birth Canal 5. Organ transplant 3. Breast Milk 6. Blood transfusion 4. Saliva (children-day care)

26. Diseases: Congenital CMV- acquired in Utero 95% asymptomatic Mother w/ primary infection  CID develops Classic cytomegalic inclusion disease CID Similar to erythroblastosisfetalis

27. Diseases: Perinatal Infections Passage birth canal/breast milk Majority asymptomatic due to ( +) Ig from mother Many continue excrete CMV in urine/saliva x years Pneumonitis Later in life  Hearing loss noted CMV- mononucleosis like illness Fever, atypical lymphos, mild hepatitis, Lymphadenopathy CMV in Immunocompromised Disseminated CMV- lungs, GIT, Retina

28. Varicella – Zoster Virus Acute Infection – Chickenpox Infects mucous membrane, skin, neurons Reactivation – Herpes zoster / shingles Self-limiting  Latent infxn in Sensory Ganglia Transmitted by Aerosols Disseminates Hematogenously Cause widespread vesicular skin lesions

29. Varicella-Zoster Virus

30. Chronic Productive Infections HIV AND HBV

31. Features of Chronic Productive Infections

32. Hepatitis B Virus- Hepadna

33. HBV- Pathogenesis HBV integrate in host genome Cause Hepatic injury is due to immune response not cytopathic effect of virus Cytotoxic T lymphocytes eliminate infected cells Evasion of immune system Inhibiting IFN-beta  downregulation of viral gene expression High mutation rate

34. HBV- Pathogenesis Chronic Infxn 5-10% Adults Up to 90 % Perinatally infected Children Carrier State Occur when CTL response is Dormant

35. Transforming Viruses

36. Transforming infection EBV ,HPV, HBV, HTLV-1

37. Epstein – Barr Virus

38. Epstein – Barr Virus

39. Atypical lymphocytes- Reactive T lymphocytes

40. Immune Response to EBV

41. Some Ac quired Defects in Cellular Immunity

42. Human Papilloma Virus

43. HPV

44. Malignant Transformation

45. Bacterial infection

46. Gram Positive Bacteria

47. Staphylococcus aureusInfection Skin Lesions Abscesses Sepsis Osteomyelitis Pneumonia Endocarditis Food Poisoning Toxic Shock Syndrome

48. Other Staph species Opportunistic infection Prosthetic valves Catheter D rug addicts Polysaccharide capsule – attach artificial materials UTI in young women Staph epidermidis Staph saprophyticus

49. Pathogenesis- Staph aureus Clumping Factor Binds fibrinogen, Fibronectin, Use as bridge Adhere host Endothelial cells Enzymes - Lipase Degrade skin lipids Protein A Binds the Fc portion of immunoglobulins – Escape Ab-mediated killing

50. Pathogenesis- Staph aureus Superantigens Stimulate 2 0 % of Lymphos Release of large amounts of TNF, IL-1  Septic Shock Toxins –Damage host cell Membrane damaging toxins

51. Exfoliative Toxins

52. staph food poisoning

53. Diseases Causesd by Staphy.

54. Streptococcal infection

55. Beta Hemolytic Strep

56. Strep Pharingitis Epiglottal swelling & abscess Cervical LN Strep Pyogenes Major antecedent of PoststrepGlomerulonephritis Ag-Ab complex deposit in glomerulus Poststrep Rheumatic fever Antistreptococcal M protein antibodies & T cells that cross react with cardiac myosin

57. Strep pyogenes:VirulenceFactors Capsules M proteins – prevents phagocytosis C5a peptidase – Degrade chemotactic C5 Antistreptococcal M protein – Ab that cross react w/ cardiac Myosin ( RHD)

58. Other Streptococcal Infection Strep. Pneumoniae Common cause of CAP & Adult Meningitis Lobar Pneumonia Otitis media, Sinusitis Often preceded by viral infection that injure ciliated epithelium Has capsule- prevent phagocytosis Pneumolysin Inserts on target cell membrane  Lysis Activates Classical pathway Reducing complement available for Opsinization

59. Beta Hemolytic Strep

60. Other Streptococcal Infection Strep. Mutans Major cause of Dental Caries Sucrose  Lactic acid  Demineralization of Tooth enamel Secrete HMW Glucans Promote Bacterial Aggregation  Plaque formation

61. Gram negative bacteria Salmonella Neisserialinfxn Whooping cough Pseudomonas Chancroid Granulomainguinale

62. Salmonella Typhi Enteric fever Transmitted From person to person Food or Contaminated water GB colonization may be associated with Gallstones Chronic Carrier State

63. Pathogenesis Survive gastric acid In the SI  Taken by M cells Engulf by macrophages in the underlying LN Reactive LN hyperplasia Disseminate by blood & Lymphatic Unlike S. enteriditidis

64. Clinical manifestation of Typhoid Fever

65. Pathogenesis- Salmonella

66. Typhoid fever Blood Culture >90% in the Febrile State Relapse may occur Systemic dissemination Encephalopathy Meningitis Seizures Endocarditis Myocarditis Pneumonia Cholecystitis Osteomyeltis

67. Neisseria Infections 2 Clinically significant species N. meningitidis N. gonorrhea

69. Spread by respiratory routeOnly small fraction develop Cause Bacterial Meningitis Children less than 2 years old

70. Pathophysiology- N. meningitidis -

71. Neisseria gonorrhea Surface pili that form barrier against phagocytosis Encapsulated gm(-) diplococci STI – Men - Urethritis, Pharyngitis, Proctitis Urethral strictures, chronic infection of Male genitals STI – Women - Salpingitis Tubo-ovarian abscess  Scar  Sterility or Ectopic pregnancy Perinatal Ophthalmic infxn

72. Neisseria gonorrhea

73. Neisseria - Evasion of immune response Use antigenic variation of OPA proteins to escape immune response A single clone of bacteria  several multiple antigenic types Pili Protein are altered by genetic recombination

74. Whooping cough Gram (-) coccobacilli Acute highly communicable Paroxysm of violent cough followed by loud inspiratory whoop Colonizes the brush border of bronchial epithelium Laryngotracheobronchitis Virulence is regulated by BVG locus

75. Virulence factor :Regulated by Bordetella virulence gene locus (bvg) PertusisExotoxins paralyze cilia

76. Pseudomonas Infection Opportunistic gram-negative bacterium Frequent, deadly pathogen of patients with cystic fibrosis, severe burns, or neutropenia. Coregulatedpili Adherence proteins that mediate adherence to epithelial cells and lung mucin Endotoxinthat causes the symptoms and signs of gram-negative sepsis.

77. Distinctive Virulence Factor

78. Distinctive Virulence Factor

79. Distinctive Virulence Factor

80. Syphilis- Treponemapallidum Sexual intercourse is the usual mode of transmission Transplacental transmission of T. pallidum occurs readily, & active disease during pregnancy results in congenital syphilis.

81. Pathology - syphilis

82. Chancre Sensored A single firm, nontender, raised, red lesion 3 weeks after contact Heals in a few weeks with or without therapy

85. Immune response to Syphlis

86. Pathogenesis of Syphilis

87. Obliterative endarteritis

88. Anaerobic Bacteria Clostridia Infection

89. Clostridial Infections Clostridium species are gram-positive bacilli There are four types of Clostridium that cause human disease: 1.Clostridium perfringens (welchii), septicum 2.Clostridium tetani 3.Clostridium botulinum 4.Costridium difficile

90. Clostridium perfringens (welchii) Anaerobic cellulitis – foul , thin discolored exudate, quick tissue destruction ( versus pyogenic ) Myonecrosis (gas gangrene)- 1to 3 days after infection Invade traumatic and surgical wounds Contaminate illegal abortions Cause uterine myonecrosis, Cause mild food poisoning, Infect the small bowel of ischemic or neutropenic patients to produce severe sepsis.

91. Clostridium tetani Proliferates in: puncture wounds umbilical stump of newborn infants Releases a potent neurotoxin, called tetanospasmin causes convulsive contractions of skeletal muscles (lockjaw).

92. Clostridium botulinum Grows in inadequately sterilized canned foods Releases a potent neurotoxin that blocks synaptic release of acetylcholine Causes a severe paralysis of respiratory and skeletal muscles (botulism).

93. Clostridium difficile Overgrows other intestinal flora in antibiotic-treated patients Releases multiple toxin Causes pseudomembranous colitis

94. Pathogenesis- Clostridium Perfringens

95. Alpha Toxin- Properties

96. Beta toxin

97. O Toxins

98. Clostridium tetani

99. Clostridium Botulinum- Neurotoxin Are released when the organisms die and autolyse Act at the peripheral nerve endings, Cleaving either synaptobrevin (as described for tetanus toxin) or synapse-associated proteins, called SNAP-25 and syntaxin.

100. Unable to release acetylcholine at the neuromuscular junction and at the synaptic ganglia and parasympathetic motor end-plates of the autonomic nervous system Descending paralysis from the cranial nerves down to the extremities.

101. Clostridium difficile Produces toxin A Which is an enterotoxin a potent chemoattractant for granulocytes toxin B a cytotoxin, which causes distinctive cytopathic effects in cultured cells and is used in the diagnosis of C. difficile infections

102. Obligate Intracellular Bacteria Chlamydia trachomatis is an obligate intracellular pathogen Venereal urethritis, lymphogranulomavenereum, and trachoma Lymphogranulomavenereum results in granulomatous inflammation of the inguinal and rectal lymph nodes. 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.

103. Malaria Intracellular protozoan parasite 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. Other types (P. vivax, P. ovale, P. malariae) Transmitted by more than a dozen species of Anopheles mosquitoes widely distributed throughout Africa, Asia, and Latin America.

104. Malaria P. vivax and P. malariae mild anemia in rare instances, splenic rupture and nephrotic syndrome. Acute P. falciparum infections produce high parasitemias, severe anemia, cerebral symptoms, renal failure, pulmonary edema, and death.

105. Features of P. falciparum Infect rbc of all ages Versus young rbc for other species High parasite burden Profound Anemia Infected rbc clump together  Stick to Endothelial lining of small blood vessels ( Sequestration )  Block blood flow Form KNOBs on rbc surface (PfEMP 1) Plasmodium falc. Eryhtrocytememb protein Bind Ligands on blood vessel wall Cause poor perfusion to the brain ( Cerebral malaria )

106. Life cycle of P. falciparum

107. Features of P. falciparum Stimulates production of HIGH levels of Cytokines Induce fever Suppress rbc production NO prodn Tissue damage Induce expression of endothelial receptors for PfEMP 1 Increasing sequestration

108. Morphology P. falciparum initially  Splenic congestion and enlargement of the spleen Infected rbc taken byreticuloendothelial cells. The liver becomes progressively enlarged and pigmented with progression of malaria. Kidneys  often enlarged and congested  pigment in the glomeruli and hemoglobin casts in the tubules.

109. Addendum Sporozoites – Infectious stage During feeding SporozoitesReleased in blood w/in minutes Bind to and invade liver cells by binding to the hepatocyte receptor for the serum proteins thrombospondin and properdin, located on the basolateral surface of hepatocytes The binding is accomplished because of the presence of sporozoite surface proteins that contain a domain homologous to the binding domain of thrombospondin. Within liver cells, malaria parasites multiply rapidly, so as many as 30,000 merozoites (asexual, haploid blood forms) Merozoites released when the hepatocyte ruptures

110. Addendum Merozoites bind by a parasite lectin-like molecule to sialic residues on glycophorin molecules on the surface of red blood cells. Merozoitesrelease multiple proteases from a special organelle called the rhoptry. Within the red blood cells, the parasites multiply in a membrane-bound digestive vacuole, Hydrolyzing hemoglobin through secreted enzymes that include an aspartate protease Most malaria parasites  rupture the cell  infect new red blood cells Some parasites sexual forms called gametocytes  infect the mosquito when it takes its blood meal.

111. Addendum 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 Sequestrins bind to endothelial cells by ICAM-1, the thrombospondin receptor, and the glycophorin CD46 cause malaria-infected red blood cells to be removed from circulation Red blood cells containing immature ring forms of the parasite  flexible  pass through the spleen, circulate in the blood Red blood cells containing mature schizonts,  rigid  sequestration in the spleen.

112. Schistosoma

113. Schistosoma S. mansoni / japonicum eggs  liver disease. 1. Substances released from schistosome eggs Are directly hepatotoxic, 2. Carbohydrate antigens from eggs induce Granuloma formation mediated by TNF and TH 1 and TH 2 helper cells. TH 2 helper T cells  secrete IL-4 Induce IgE synthesis eosinophilia, mastocytosis, and high levels of serum IgE in human schistosomiasis Resistance to reinfection by schistosomes after treatment correlates with IgE levels Whereas eosinophil major basic protein may destroy larval schistosomula

114. 3. Eggs release factors that stimulate lymphocytes secrete a fibrogeniclymphokine Stimulates fibroblast proliferation and portal fibrosis. This exuberant periportal fibrosis, which is out of proportion to the injury caused by the eggs and granulomas, Pipestem Fibrosis Occurs in 5% - 10% of persons heavuly infected with schistosomes Hallmarks of severe schistosomiasis: Portal hypertension Esophageal varices, Ascites

115. Pipestem Fibrosis - Liver

116. S. haematobium infection, Bladder inflammatory patches due to massive egg deposition and granulomas cause hematuria The most frequent complication is inflammation and fibrosis of the ureteral walls leading to obstruction, hydronephrosis, and chronic pyelonephritis.

117. Schisoma eggs