Infectious Part 1

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Infectious Part 1

  1. 1. Infectious Diseases<br />Amelia Co-Fibra MD, FPSP<br />
  2. 2. Tell me<br />
  3. 3. How is this possible?<br />
  4. 4.
  5. 5. UNDERSTANDING PATHOGENESES OF INFECTIOUS AGENTS<br />1. Enumerate the categories of Infectious agents and their general features<br />2. Know the different human barriers against infectious agents<br />3. To enumerate and understand the Transmission & Dissemination of microbes<br />4. To know how microbes cause disease<br />A. VIRAL INJURY<br />B. BACTERIAL INJURY<br />C. INJURIOUS EFFECTS OF HOST IMMUNITY<br />COURSE OUTLINE<br />
  6. 6. KNOW DISEASES PRODUCED BY SOME OF THE INFECTIOUS AGENTS<br />A. VIRAL INFECTION<br />B. BACTERIAL INFECTION<br />C. PARASITES<br />D. FUNGAL<br />COURSE OUTLINE<br />
  7. 7. Categories of Infectious Agents<br />PRIONS <br />VIRUSES<br />BACTERIOPHAGES/ PLASMIDS/ TRANSPOSON<br />BACTERIA<br />CHLAMYDIA / RICKETTSIAE/ MYCOPLASMA<br />FUNGI<br />PROTOZOA<br />HELMINTHS<br />ECTOPARASITES<br />
  8. 8. Classes of Human Pathogens<br />
  9. 9. PRIONS<br />Nucleic acid free<br />Spontaneous mutation or Inherited Mutation in PrP<br />Cause Transmissible Spongiform Encephalitis<br />
  10. 10. Pathophysiology<br />Abnormal PrP promotes transformation of normal PrP to abnormal forms<br />EXPLAINING THE INFECTIOUS NATURE OF THESE DISEASE<br />
  11. 11. Cause Transmissible Spongiform encephalitis<br />Kuru ( Human Cannibalism )<br />Bovine Spongiform Encephalitis ( Mad Cow Disease )<br />Creutzfeldt-Jacob Disease (Spontaneous - Sporadic/ Inherited -Familial)<br />Transmitted <br />From corneal/ organ transplant<br />BSE infected cattle<br />Blood Transfusion<br />Vacuolization of gray matter but no inflammation<br />Clinical presentation<br />
  12. 12. Obligate Intracellular<br />20-300nm<br />May aggregate forming inclusion bodies<br />CMV – large eosinophilic inclusion<br />Nucleic acid core surrounded by capsid<br />Cause <br />Transient illness ( colds, influenza)<br />Not eliminated  persist w/in cells<br />Continue to multiply ( HEPATITIS B )<br />Non-replicating OR Latent ( chickenpox shingles)<br />May transform host cell  tumor / cancer cell<br /> ( Human papilloma virus )<br />VIRUSES<br />
  13. 13. Mobile genetic elements that infect bacteria<br />Indirectly cause human diseases<br />Encodes virulence factor<br />Exchange of these elements between bacteria<br />Bacteriophages/ plasmids<br />Converts Nonpathogens Pathogens<br />Plasmids/ Transposons<br />Encode antibiotic resistance<br />Eg. Vancomycin – resistant enterococci<br />BACTERIOPHAGE, PLASMIDS, TRANSPOSONS<br />
  14. 14. Bacteria<br />Prokaryotes – have cell membrane<br />Gram positive - thick wall surrounding the cell membrane (stain violet )<br />Gram negative - thin cell wall sandwich between 2 phospholipidbilayer membranes <br />( stain red )<br />Lack Nuclei<br />Most synthesize their own DNA/RNA <br />Depend on host for Favorable Environment<br />Intracellular or Extracellular<br />
  15. 15. CHLAMYDIA, RICKETTSIAE, MYCOPLASMA<br />Divide by binary fusion<br />Mycoplasma<br />Lack cell wall <br />Mycoplasma are tiniest living organism<br />Airborne transmission<br />Binds surface epithelial cells in airway<br />Chlamydia <br />Lack metabolic capabilities (ATP) <br />Chlamydia & Rickettsia Obligate intracellular organism<br />Mulitply in vacuoles inside the cell<br />
  16. 16. FUNGI<br />PROTOZOA<br />Eukaryotes – thick chitin walls & ergosterol membrane<br />Most exhibit Thermal Dimorphism <br />HEALTHY PERSONS<br />Dermatophytes – skin<br />Subcutaneous tissue abscess & granulomas<br />IMMUNOCOMPROMISED<br />Deep fungal infxn  invade tissues <br />AIDS<br />Lethal Pneumonia by Opportunistic Pneumocystiscarinii<br />Single-celled eukaryotes<br />Trichomonasvaginalis<br />Intestinal protozoa<br />Blood borne protozoa<br />Plasmodium spp<br />
  17. 17. HELMINTHS<br />ECTOPARASITES<br />Multicellular organism<br />Life cycle<br />Roundworms- Nematodes<br />ASCARIS<br />FILARIA/ TRICHINELLA<br />Flatworms- Cestodes<br />Tapeworms<br />Flukes – Trematode<br />Schistosoma<br />Arthropods<br />Lice<br />Ticks<br />Bedbugs<br />Live on the skin<br />May be vectors for other pathogens<br />Lyme disease by ticks<br />
  18. 18. TRANSMISSION & DISSEMINATION OF MICROBES<br />ROUTES OF ENTRY <br />Spread & Dissemination<br />Release of Microbes<br />Sexually Transmitted Infection<br />
  19. 19. HOST BARRIERS TO INFECTION & ROUTES OF ENTRY<br />
  20. 20. SKIN<br />
  21. 21. GIT- Barrier<br />
  22. 22. GIT-Infection <br /><ul><li>Local Defenses Weaken
  23. 23. Low gastric acidity
  24. 24. Antibiotics
  25. 25. Stalled peristalsis
  26. 26. Organism develop strategies to overcome defenses
  27. 27. Nonenveloped viruses may resist digestive enzymes - HAV, Rotavirus
  28. 28. Cyst form – Protozoans</li></li></ul><li>RESPIRATORY<br />
  29. 29. Respiratory Pathogens<br />Influenza Virus<br /> (+) Hemagglutinin proteins on surface  bind sialic acid on epithelium of host  engulf by cell  virus replicate inside cell<br />(+) Neuramidase<br />Cleaves sialic acid – Allow viral release from cell<br />Lowers the viscosity of the mucus  facilitates viral transit<br />Staphyloccoci ( Secondary Infection )<br />Gain access to host cell after viral infxn cause loss of ciliated epithelium<br />
  30. 30. UROGENITAL<br />
  31. 31. Spread & Dissemination of Microbes<br />
  32. 32. 1. Proliferate Locally at the site<br />Adhere & Proliferate in/on Epithelial Cells<br />HPV , Dematophytes<br />Confined to Lumen of Hallow Viscera<br />Cholera<br />Spread & Dissemination of Microbes<br />
  33. 33. Spread & Dissemination of Microbes<br />2. Penetrate the epithelial barrier  Spread via Hematogenous or Lymphatic or Nerve<br />Invasiveness Due to:<br />Motility<br />Secrete Lytic enzymes- Hyaluronidase<br />Degrades extracellular matrix between cells<br />Strep & Staph<br />Initial spread  Follow tissue Planes of Least Resistance  Regional LN  Blood Stream  Distant organs <br />Abscess  Regional LNs  Bacteremia  Colonize distant organs<br />
  34. 34. Spread & Dissemination of Microbes<br />HEMATOGENOUS SPREAD<br />FREE - Polio, HBV, fungi, protozoa<br /> W/in WBC – HSV, HIV, TB<br />W/in RBC - Plasmodium<br />Nerve<br />
  35. 35. Spread & Dissemination of Microbes<br />3. Viral Propagation<br />A). Propagate from Cell to Cell by replication<br />B). Propagate By Fusion or Transport within Nerves – Rabies, VZV<br />4. Placental – Fetal Route<br />Bacterial / MycoplasmaPlacentitis<br />Premature delivery<br />Maldevelopment - Rubella<br />Severe in Early trimester<br />Syphilis affect mother late in 2nd Trimester<br />Passage to birth canal- Gonococcal, Chlamydia<br />Maternal Milk – CMV, HBV, HTLV-1<br />
  36. 36. Maternal transmission <br /> HIV – Major cause of AIDS in children<br />HBV – Can later cause Chronic Hepatitis & Liver Ca<br />Notes:<br />
  37. 37. Release of Microbes from the Body<br />Important in the Transmission<br />
  38. 38. Release of Microbes from the Body<br /><ul><li>Release depends on the Location</li></ul>Skin shedding <br />Coughing <br />Sneezing<br />Voiding – urine/ feces<br />Insect vector<br />
  39. 39. Respiratory<br />Viruses & Bacteria <br />Infectious only when lesions are open to AIRWAYS<br />Fecal-oral<br />Water-borne viruses<br />HAV, HEV, Polio, Rotaviruses<br />Saliva<br />EBV, CMV, Mumps<br />Larval penetration<br />Hookworms, Schistosomiasis<br />Transmission- Person to Person<br />
  40. 40. Sexual / Prolonged Intimate or Mucosal Contact<br />Viruses - HPV, HSV, HBV, HIV<br />Bacteria – Syphilis, Gonorrhea, Chlamydia<br />Protozoan – Trichomonas<br />Candida<br />Blood & Blood products/ Needle pricks, etc<br />HBV, HCV, HIV<br />Transmission- Person to Person<br />
  41. 41. Direct Contact or Consumption of Animal products<br />Indirectly via an Invertebrate vectors<br />Insects, Ticks, Mites<br />Transmission – Animals to HumanZOONOTIC INFECTIONS<br />
  42. 42. SEXUALLY TRANSMITTED INFECTONS<br />
  43. 43. Sexually Transmitted InfectionS<br /><ul><li>Transmitted through Sexual Contact
  44. 44. Chlamydia & Neisseria – Usually by sexual intercourse
  45. 45. Shigella & Entamoeba – Occasionally spread by sex
  46. 46. High Risk Groups for STI</li></ul>Adolescent<br />Men with Men<br />Illegal drug user<br />
  47. 47. <ul><li>Organism tend to be short lived outside the host
  48. 48. Usually dependent on Direct person to person spread
  49. 49. Initial site of infection – urethra, vagina, rectum, oropharynx
  50. 50. Most are Asymptomatic carriers</li></ul>STI <br />
  51. 51. <ul><li> STI increases the Risk for additional STI’s - Coinfection
  52. 52. Risk factors are the same for all STI’s
  53. 53. Biologic interaction between them  Increase the spread of infxn
  54. 54. Gonococcalcervicitis  local tissue damage  Increased chance of HIV infxn
  55. 55. STI  Vertical Spread
  56. 56. C. trachomatis – conjunctivitis
  57. 57. Neonatal Herpes simplex – visceral&CNS</li></ul> disease <br /><ul><li> Syphilis – miscarriage</li></li></ul><li>HOST DEFENSES AGAINST INFECTIONS<br />
  58. 58. VIRULENCE<br />Ability of microbe to infect , colonize, damage host tissues<br />HOST RESISTANCE <br />Ability of host defense mechanisms to eradicate infection – Innate & Adaptive Immune Defenses<br />Outcome of Infection – Determined <br />
  59. 59. INNATE DEFENCES<br />Physical Barriers<br />Macrophages<br />NK cells<br />Plasma Proteins – Complement , Cytokines, Acute phase reactants<br />Adaptive Immune response<br />Are stimulated by exposure to microbes<br />Increase in magnitude, speed & effectiveness with successive exposure<br />Mediated by T & B lymphocytes and their products<br />Immune Defenses<br />
  60. 60. HOW MICROORGANISMS CAUSE DISEASE<br />DIRECT LY CAUSE CELL DEATH<br />TOXIN / ENZYME RELEASE<br />INDUCE CELLULAR RESPONSES<br />
  61. 61. MECHANISMS OF VIRAL INJURY<br />
  62. 62. Tissue Tropism<br />Predilection of virus to infect certain cells and not others.<br />Tropism Determined : <br />HOST CELL RECEPTOR- MAJOR DETERMINANT<br />CELLULAR TRANSCRIPTION FACTORS<br />That Recognize Viral Enhancer & Promoter Sequences<br />Allow Viral replication inside the cell<br />ANATOMIC BARRIER<br />LOCAL TEMPERATURE<br />pH<br />HOST DEFENSE<br />
  63. 63. 1. Binding to host cell surface proteins<br />Viruses possess specific cell-surface PROTEINS<br />Viruses may use Normal Cellular Receptors of Host<br />Host Proteases are Needed  For Binding <br />Host Proteases Cleaves & Activates Influenza Hemagglutinin<br />2. Translocation into cytosol<br />3. Replication via virus specific enzymes<br />Viruses Enter Host<br /> (+) Hemagglutinin proteins on surface  bind sialic acid on epithelium of host  engulf by cell  virus replicate inside cell<br />(+) Neuramidase– lowers the viscosity of the mucus  facilitates viral transit<br />
  64. 64. Mechanism of Viral injury<br />
  65. 65. Cytopathic Effects - Virus Kill Cell Directly <br />
  66. 66. Inducing Host immune response to virus – infected cells <br />Host (CTL) Lymphocytes attack virus-infected cells<br />FAS Ligand on CTL binds FAS receptor in liver cells<br />Eg. Hepatitis B virus<br />Virus Damage Cell involved in Host Antimicrobial Defense  Secondary Infections<br />Viral killing of one cell type cause the death of the other cells<br />Motor denervation  atrophy of the muscles<br />Antiviral Immune responses<br />
  67. 67. 1. ABORTIVE<br />2. LATENT<br />3. PERSISTENT<br />Viral Infection can be:<br />
  68. 68. BACTERIAL INJURY TO HOST TISSUES <br />Bacterial Virulence<br />ADHERE TO HOST CELLS  ENTRY<br />DELIVER TOXINS<br />Virulence of Intracellular Bacteria<br />
  69. 69. Mechanism of Bacterial Injury<br />
  70. 70. Virulence genes<br />Plasmids & Bacteriophage<br />Mobile genetic elements <br />Spread between bacteria<br />Encode virulence factors – Abtic resistance, toxins<br />Quorum sensing<br />Induce expression of virulence factor as their concentration in tissues increases<br />Eg. Staph aureus - abscess<br />Biofilm formation<br />Live in viscous layer of extracellular material<br />Enhance adherance & Inaccesible<br />IV catheters, Artificial joints<br />Bacterial Virulence<br />
  71. 71. Bacterial Adherence<br />
  72. 72. Bacterial Adherence<br />
  73. 73. Infect either<br />Epithelial cells – Shigella, Invasive E. coli<br />Macrophages – Mycobacteria<br />Both – S. typhi<br />Escape immune system- TB<br />Facilitate spread<br />Interact w/ cell<br />Inhibit host CHON synthesis – Shigella & E.coli<br />Blocks fusion of acidic lysosome to form phagosome – M.TB<br />Virulence of Facultative Intracellular Bacteria<br />
  74. 74. Some Mechanisms of Bacterial Entry to Cell<br />
  75. 75. Some Mechanisms of Bacterial Entry to Cell<br />
  76. 76. Inhibit host protein synthesis  Replicate rapidly  Lyze host cell w/in 6 hours<br />Blocks fusion of lysosome with phagosome  allow bacteria to replicate unchecked w/in macrophages<br />Effect of Bacteria inside the cell<br />
  77. 77. Bacterial Toxins<br />
  78. 78. Lipopolysaccharides<br />Large outer cell wall of gram negative<br />Response of Host<br />Beneficial<br />Detrimental<br />ENDOTOXINS<br />
  79. 79. Lipopolysaccharide- Beneficial EffectActivates immune response<br />
  80. 80. Lipopolysaccharide-Harmful Effect<br />
  81. 81. Exotoxin- Secreted proteins<br />1. ENZYME - Protease staph.<br />Split epidermis from dermis<br />2. TOXINS – with A-B toxins<br />A subunit – enzymatic activity<br />INACTIVATES HOST PROTEINS – Cholera/Diptheria<br />DEGRADES HOST PROTEINS - Botulinum<br />B-subunit – binding receptor & delivers <br /> A subunit to the cell<br />
  82. 82. 3. Neurotoxins – Clostridium botulinum & tetani<br />Inhibit release of neurotransmitters<br />But do not kill neurons<br />4. Superantigens – staph aureus, strep pyogenes<br />Stimulate very large T-lymphos Lead to very high lymphocyte proliferation and cytokine release  Capillary leak  shock <br />Exotoxin<br />
  83. 83. INJURIOUS EFFECTS OF HOST IMMUNITY<br />
  84. 84. TB  Granulomatous inflammation ( Delayed Hypersensitivity Reaction )<br />Prevents spread of microbe<br />But cause tissue Damage & Fibrosis<br />HepaB Immune response  Liver damage <br />Beta hemolytic Strep<br />  Ab against M protein  Cross react w/ cardiac proteins  RHD<br /> Ag + ASO (anti streptococcal antibodies)  Deposit in renal glomeruli causing  PoststreptococcalGlomerulonephritis<br />Immune response  Tissue injury<br />
  85. 85. IMMUNE EVASION BY MICROBES<br />
  86. 86. Remaining inaccessible to host immune response<br />Varying or shedding antigens<br />Resisting innate immune defenses<br />Preventing T-cell activation <br />Impairing effective T-cell antimicrobial responses by specific or non-specific immunosuppression<br />Mechanism of Immune evasion by Microbes<br />
  87. 87.
  88. 88. Propagate in the lumen of <br />Intestine – Clostridium difficile<br />Gallbladder – Salmonella typi<br />Shed from luminal surface of epithelial cells<br />CMV- urine, milk<br />Polio – stool<br />Infect the keratinized skin – Pox virus<br />Infect Host cell – malaria<br />Encyst in tissues – tapeworms<br />Viral Latency – many viral genes are not expressed<br />Inaccessible to Host Immune <br />
  89. 89. Varying antigens / Shedding antigens<br />Low fidelity of Viral RNA polymerases<br />HIV<br />Reassortment of viral genomes<br />Influenza virus<br />Different capsular polysaccharides<br />Strep Pneumoniae<br />Shed antigens w/in minutes of penetrating the skin Preventing recognition by antibodies <br />Schistosomamansoni<br />
  90. 90. Resisting Innate Immune Response<br />CAMP Resistance<br />Cationic antimicrobial peptides ( CAMP )<br />Defensin, Cathelicidins<br />Initial defense against invading microbes<br />Enabling them to avoid killing by pmns & macropahges<br />Carbohydrate Capsule<br />Pneumococcus, Meningococcus, Hemophilus<br />PREVENTI PHAGOCYTOSIS<br />K1 capsule containing sialic acid<br />E. coli- meningitis<br />Sialic acid will not bind C3b ( alternate complement pathway)<br />
  91. 91. Covering them with host proteins<br />Staph aureus covered by A molecules that bind Fc portion inhibit Phagocytosis<br />Protease<br />Degrade antibodies <br />Neisseria, Hemophilus, Streptococcus<br />Replicating w/in phagocytic cells<br />Mycobacterium, cryptococcus<br />Resisting Innate Immune Response<br />
  92. 92. Some viruses block complement activation<br />HERPESVIRUSES, POXVIRUS<br />Produce homologues of IFN/ IFN receptors <br />INHIBIT THE ACTION OF SECRETED IFN<br />Produce cytokine mimics<br />EBV – homologue of IL 10 ( Bind & Inhibit secreted IFN )<br />Resisting Innate Immune Response<br />
  93. 93. Decrease Recognition of Infected cells by CD4 , CD8<br />
  94. 94. Decrease Recognition of Infected cells<br />
  95. 95. Decrease Recognition of Infected cells<br />
  96. 96. Immunosuppression<br />

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