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Infectious Part 1
 

Infectious Part 1

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    Infectious Part 1 Infectious Part 1 Presentation Transcript

    • Infectious Diseases
      Amelia Co-Fibra MD, FPSP
    • Tell me
    • How is this possible?
    • 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
    • KNOW DISEASES PRODUCED BY SOME OF THE INFECTIOUS AGENTS
      A. VIRAL INFECTION
      B. BACTERIAL INFECTION
      C. PARASITES
      D. FUNGAL
      COURSE OUTLINE
    • Categories of Infectious Agents
      PRIONS
      VIRUSES
      BACTERIOPHAGES/ PLASMIDS/ TRANSPOSON
      BACTERIA
      CHLAMYDIA / RICKETTSIAE/ MYCOPLASMA
      FUNGI
      PROTOZOA
      HELMINTHS
      ECTOPARASITES
    • Classes of Human Pathogens
    • PRIONS
      Nucleic acid free
      Spontaneous mutation or Inherited Mutation in PrP
      Cause Transmissible Spongiform Encephalitis
    • Pathophysiology
      Abnormal PrP promotes transformation of normal PrP to abnormal forms
      EXPLAINING THE INFECTIOUS NATURE OF THESE DISEASE
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • TRANSMISSION & DISSEMINATION OF MICROBES
      ROUTES OF ENTRY
      Spread & Dissemination
      Release of Microbes
      Sexually Transmitted Infection
    • HOST BARRIERS TO INFECTION & ROUTES OF ENTRY
    • SKIN
    • GIT- Barrier
    • GIT-Infection
      • Local Defenses Weaken
      • Low gastric acidity
      • Antibiotics
      • Stalled peristalsis
      • Organism develop strategies to overcome defenses
      • Nonenveloped viruses may resist digestive enzymes - HAV, Rotavirus
      • Cyst form – Protozoans
    • RESPIRATORY
    • 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
    • UROGENITAL
    • Spread & Dissemination of Microbes
    • 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
    • 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
    • Spread & Dissemination of Microbes
      HEMATOGENOUS SPREAD
      FREE - Polio, HBV, fungi, protozoa
      W/in WBC – HSV, HIV, TB
      W/in RBC - Plasmodium
      Nerve
    • 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
    • Maternal transmission
      HIV – Major cause of AIDS in children
      HBV – Can later cause Chronic Hepatitis & Liver Ca
      Notes:
    • Release of Microbes from the Body
      Important in the Transmission
    • Release of Microbes from the Body
      • Release depends on the Location
      Skin shedding
      Coughing
      Sneezing
      Voiding – urine/ feces
      Insect vector
    • 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
    • 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
    • Direct Contact or Consumption of Animal products
      Indirectly via an Invertebrate vectors
      Insects, Ticks, Mites
      Transmission – Animals to HumanZOONOTIC INFECTIONS
    • SEXUALLY TRANSMITTED INFECTONS
    • Sexually Transmitted InfectionS
      • Transmitted through Sexual Contact
      • Chlamydia & Neisseria – Usually by sexual intercourse
      • Shigella & Entamoeba – Occasionally spread by sex
      • High Risk Groups for STI
      Adolescent
      Men with Men
      Illegal drug user
      • Organism tend to be short lived outside the host
      • Usually dependent on Direct person to person spread
      • Initial site of infection – urethra, vagina, rectum, oropharynx
      • Most are Asymptomatic carriers
      STI
      • STI increases the Risk for additional STI’s - Coinfection
      • Risk factors are the same for all STI’s
      • Biologic interaction between them  Increase the spread of infxn
      • Gonococcalcervicitis  local tissue damage  Increased chance of HIV infxn
      • STI  Vertical Spread
      • C. trachomatis – conjunctivitis
      • Neonatal Herpes simplex – visceral&CNS
      disease
      • Syphilis – miscarriage
    • HOST DEFENSES AGAINST INFECTIONS
    • 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
    • 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
    • HOW MICROORGANISMS CAUSE DISEASE
      DIRECT LY CAUSE CELL DEATH
      TOXIN / ENZYME RELEASE
      INDUCE CELLULAR RESPONSES
    • MECHANISMS OF VIRAL INJURY
    • 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
    • 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
    • Mechanism of Viral injury
    • Cytopathic Effects - Virus Kill Cell Directly
    • 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
    • 1. ABORTIVE
      2. LATENT
      3. PERSISTENT
      Viral Infection can be:
    • BACTERIAL INJURY TO HOST TISSUES
      Bacterial Virulence
      ADHERE TO HOST CELLS  ENTRY
      DELIVER TOXINS
      Virulence of Intracellular Bacteria
    • Mechanism of Bacterial Injury
    • 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
    • Bacterial Adherence
    • Bacterial Adherence
    • 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
    • Some Mechanisms of Bacterial Entry to Cell
    • Some Mechanisms of Bacterial Entry to Cell
    • 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
    • Bacterial Toxins
    • Lipopolysaccharides
      Large outer cell wall of gram negative
      Response of Host
      Beneficial
      Detrimental
      ENDOTOXINS
    • Lipopolysaccharide- Beneficial EffectActivates immune response
    • Lipopolysaccharide-Harmful Effect
    • 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
    • 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
    • INJURIOUS EFFECTS OF HOST IMMUNITY
    • 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
    • IMMUNE EVASION BY MICROBES
    • 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
    • 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
    • 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
    • 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)
    • 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
    • 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
    • Decrease Recognition of Infected cells by CD4 , CD8
    • Decrease Recognition of Infected cells
    • Decrease Recognition of Infected cells
    • Immunosuppression