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