Micro Others

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Micro Others
2012-03-21 21:24:54
Micro Other bacteria

Micro Other bacteria
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  1. Acid Fast Bacteria
    • Mycobacterium
    • Corynebacterium
    • Norcardia
    • "My CoroNary"
  2. Mycobacterium
    • Gram-exceptions (Gram stain not applicable)
    • o Thick Unique cell wall:
    • Acid Fast (20% Peptidoglycan& 60% lipids-waxy)
    •  Slow Growth (due to thickness of cell wall)
    • o Order of Mycobacterial cell wall
    • Layer 1: LAM (green) (lipoarabinomannan) and surface glycoproteins
    • • Contains Cord Factor (virulent M. TB)
    • Layer 2: mycolic acid (purple)
    • Layer 3: arabinogalactan (brown)
    • Layer 4: peptidoglycan (lavender)
  3. Langhans Cells
    • (M. Tuberculosis)
    • Large cells found in granulomatous conditions.
    • Fusion of epithelioid cells (macrophages)
    • horseshoe-shaped nuclei in periphery
    • (Latent TB)
  4. Active TB
    • liquefaction-caseous center enlarges, fills w/ air
    • TB multiply until rupture into bronchiole and disseminate
  5. Ziehl-Neelsen method
    • acid-fast(M. TB) detection in sputum
    • also use Lowenstein-Jensen agar for TB
  6. Mantoux Test
    • Tuberculin, subQ test.
    • M. Tuberculosis
    • 10mm> = +
  7. BCG (Bacille Calmette Guerin) vaccine
    • weakened M. bovis
    • not 100% effective against TB
    • not used in US
  8. M. tuberculosis
    • Facultative intracellular (macrophages)
    • Virulence Factors:
    • • Cord Factor
    • • Intracellular growth ability in lung alveolar macrophages
    • • No exotoxins
    • • Disease symptoms mostly caused by immune reaction to infection
    • Epidemiology:
    • person-to-person spread by infectious aerosols
    • 1/3 worldwide infected leading bacteria infection cause of death
    • Diseases:
    • Latent TB: no symptoms, can’t spread to others
    • macrophage fusion (Langhan’s cells),
    • leads to (granuloma or tubercle), central caseous necrosis
    • and ultimate calcification.
    • Active TB: symptoms (lung), can spread TB to others and disseminate
    • Pott’s Disease-TB of the spine
    •  Lab Diagnosis:
    • Ziehl-Neelsen method (acid-fast bacilli detection)
    • Lowenstein-Jensen agar3-8 weeks to get visual colonies because of cell wall
    • Mantoux test (PPDPurified Protein Derivative)
    • treat w/ multiple drugs
    • -----------------
    • Mycobacterium
    • Gram-exceptions (Gram stain not applicable)
    • o cell wall is impressively thick and unique in its complex composition, which is responsible for many of the characteristic properties of the bacteria
    •  Acid Fast
    •  Slow Growth (due to thickness of cell wall)
    • o Order of Mycobacterial cell wall
    •  Layer 1: LAM (green) and surface glycoproteins
    • • Contains Cord Factor (responsible for the cord-like appearance of M. TB
    • • Virulent strains of M. TB have cord factor on their surfaces, whereas avirulent strains do not
    •  Layer 2: mycolic acid (purple)
    •  Layer 3: arabinogalactan (brown)
    •  Layer 4: peptidoglycan (lavender)
  9. Lepromatous leprosy
    • disfiguring skin lesions, nodules, thickened dermis, etc
    • high infectivity, lots of bacteria in lesions
    • Microscopy detection
    • combined antibiotics (early)
    • Enormous numbers in the deep layers of the affected skin, and they spread widely through the skin's lymphatic channels.

  10. Tuberculoid Leprosy
    • nodular or cutaneous leprosy
    • low infectivity, few bacteria in lesions
    • no microscopy detection
    • inflamed, red, well-defined plaques that infiltrate the nervous tissue causing a loss of skin sensation as well as sensorimotor damage to nerves serving the area.
  11. M. leprae
    • Facultative Intracellular Pathogen
    • Acid Fast
    • NO in vitro culture system
    • Humans and armadillos=natural hosts
    • P2P-direct, inhalation
    • Diseases:
    • Leprosy (Hansen’s Disease): skin, mucous membranes and nerves
    • o Tuberculoid Leprosy (cutaneous leprosy, nodular leprosy)
    •  Low infectivityfew bacteria in lesions
    • o Lepromatous Leprosy
    •  High infectivitylots of bacteria in lesions
    • ----------------------
    • Mycobacterium
    • Gram-exceptions (Gram stain not applicable)
    • o cell wall is impressively thick and unique in its complex composition, which is responsible for many of the characteristic properties of the bacteria
    •  Acid Fast
    •  Slow Growth (due to thickness of cell wall)
    • o Order of Mycobacterial cell wall
    •  Layer 1: LAM (green) and surface glycoproteins
    • • Contains Cord Factor (responsible for the cord-like appearance of M. TB
    • • Virulent strains of M. TB have cord factor on their surfaces, whereas avirulent strains do not
    •  Layer 2: mycolic acid (purple)
    •  Layer 3: arabinogalactan (brown)
    •  Layer 4: peptidoglycan (lavender)
  12. Spirochetes
    • Long, thin and helical
    • Motile by axial filaments (endoflagella or periplasmic flagella)
    • o Endoflagella is located within the periplasm between the petidogylcan and the outer membrane
    • Treponema Pallidum
    • Borrelia burgdoferi
    • Leptospira interrogans
  13. Syphilis
    • 1. Primary - zipper cut
    • 2. Secondary - rash
    • 3. Tertiary-GUMMA (granulomas, anywhere)
    • Congenital-miscarage, death, or desquamation for baby, rarely develop into late-stage unnoticed)
    • Hutchinson's Teeth-notched, narrow central incisors
  14. RPR test
    • Rapid plasma reagin VDRL
    • cardiolipin from damaged cells mitochondria
    • forms black aggregates
    • Not specific for T.pallidum (any tissue damage)
  15. Syphillis Treatment
    • T pallidum
    • Penicillin
    • Tetracycline or doxycycline (allergic to penicillin)
  16. T pallidum lab diagnosis
    • Dark-field Microscopy
    • Serological Tests
    • Rapid plasma reagin (RPR or VDRL): Ab test
    • Treponemal test-Fluorescent treponemal antibody-absorption (FTA-Abs) test: IgG flourescent binding
    • T. pallidum particle agglutination (TP-PA) - geletin with surface antigens
  17. Treponema Pallidum
    • Facultative intracellular pathogen
    • No in vitro culture system available
    • Causes STD Syphillis
    • o Virulence Factors:
    • Intracellular growth ability
    • Tissue destruction from immune response
    • o Epidemiology:
    • Humans only natural host
    •  Spread by Direct sexual contact
    • Can’t be spread through contact with inanimate objects because organism is extremely labile
    • • Congenital transmission or transfusion with contaminated blood
    • o Diseases:
    •  Primary Syphilliszipper
    •  Secondayr Syphillis: rash
    •  Tertiary (late) SyphillisGumma (glanuloma)
    • • Most devastating because completely internal
    • Cancerous cell growth
    • Congenital Syphillisoccurs when child is born to a mother with secondary or tertiary syphilis
    • o Lab Diagnosis:
    •  Primary Syphilis: Dark field microscopy
    •  Secondary and Tertiary: Serological tests
    • • Nontreponemal Test: Rapid Plasma Reagin (RPR) test or (VDRL test)indirect
    • o Tests for presences of antibodies against cariolipin
    • o Less specific, not specific for T. pallidum
    • • Treponemal testDirect:
    • o fluorescent treponemal antibody-absorption (FTA-Abs) test
    • o T. pallidum partical agglutination (TP-PA) Test
    • ==================
    • Spirochetes
    • o Long, thin and helical
    • o Motile by axial filaments (endoflagella or periplasmic flagella)
    • o Endoflagella is located within the periplasm between the petidogylcan and the outer membrane
  18. Barbour-Stoenner-Kelly (BSK)
    B. burgdorferi @32°C
  19. bull’s-eye rash
    • B. burgodferi
    • erythema chronicum migrans
  20. Borrelia burgdoferi
    • o Can survive without iron
    • o True Zoonotic Pathogen
    •  Deer ticks (deer&mouse reservoirs)
    • o Causes Lyme Disease (doxycycline, penicillin)
    •  Most common tick-borne disease
    •  1st stage: “bull’s-eye” rash
    •  2nd stage: flu-like symptoms
    •  3rd stage: arthritis and disorders of the nervous system and heart
    • o Lab Diagnosis: Barbour-Soenner-Kelly (BSK) medium at 32 degrees C
    • =================
    • Spirochetes
    • o Long, thin and helical
    • o Motile by axial filaments (endoflagella or periplasmic flagella)
    • o Endoflagella is located within the periplasm between the petidogylcan and the outer membrane
  21. Leptospira interrogans
    • o Characteristic hooked ends
    • obligate aerobic
    • o True zoonotic pathogen (rodents)
    • o Diseases:
    • Letospirosis or Weil’s disease•
    • Associated with jaundice (lead to kidney damage)
    • ==============
    • Spirochetes
    • o Long, thin and helical
    • o Motile by axial filaments (endoflagella or periplasmic flagella)
    • o Endoflagella is located within the periplasm between the petidogylcan and the outer membrane
  22. Weil-Felix reaction
    agglutination test of the genus Proteus that have antigens in common with Rickettsia
  23. Rocky Mountain spotted fever
    • Tetracycline
    • Rash begins on palms and soles, ankles/wrists and spread to trunk
    • –Acute onset of fever, headache,
    • myalgia, abdominal pain
    • –can be fatal if untreated
  24. Rickettsia
    • Obligate->Endothelial Cells
    • o Subdivided into two groups:
    • Spotted Fever Group-replicates in both the nucleus and cytoplasm, Actin Tail
    • Typhus Group: cytoplasm, lysis
    • tissue or embryo cultures
    • • R. rickettsii-Rocky Mountain Spotted Fever (fatal if not treated)
    • o True zoonotic pathogen
    • Tick-borne bacterial pathogen
    • o Survives host’s immune system by escaping from phagosome
    • o Exits host cell via actin tail
    • o Lab Diagonsis: Weil-Felix reaction
    •  Use particular strains of Proteus that have antigens in common with rickettsias to be identified
    •  Typhus groupreplicates in the cytoplasm only
    • o Exits host cell via lysis of cell
    • o Virulence Factors: intracellular growth abilityEntry, escape from pahgosome, exit
  25. Morulae
    • phagocytosed membrane-enclosed masses of Ehrlichia chaffeensis
    • inhibits phagolysosome formation
    • HME( Human monocytic ehrlichiosis) (doxycycline)
    • inin
  26. Ehrilichia
    • Obligate->Monocytes
    • cocci similar to G-
    • o Virulence Factors
    •  Intracellular growth ability
    •  Create membrane-enclosed masses called morulae (can be used for diagnosis)
    • o Epidemiology:
    •  True Zoonotic Pathogen (deer, rodents, canines)
    • Tick-Borne Bacterial Pathogen (Atlantic)
    • o E. chaffeensis
    •  Causes Human monocytic ehrlichiosis (HME) (Doxycycline)
    • • Associated with a decrease in white blood cells (leukopenia)
    •  Survives host’s immune system by preventing fusion of phagosomes with lysosomes
  27. Coxiella
    • Obligate->Macrophages
    • pleomorphic coccobacillus
    • o Evolves to “spore-like form” that can survive in nature for many months
    • o C. burnetii
    •  Virulence factors:
    • • Intracellular
    • • Can survive and replicate in acidic environment of phagolysosome
    • • Extracellular form extremely stable
    • Epidemiology:
    • • True Zoonotic Pathogen (mammals,birds)
    •  Diseases:
    • Q-Fever: chronic ->endocarditis , tetracyclines
  28. Chlamydial Lifecycle
  29. Bacterial STD pathogens
    • Neisseria gonorrhoeae: gonorrhea (purulent discharge)
    • –Gram negative coccus
    • Haemophilus ducreyi: chancroid (painful ulcer)
    • –Gram negative bacillus
    • Treponema pallidum: syphillis (chancre, rash, gumma)
    • –Facultative intracellular pathogen
    • –Spirochete
    • Chlamydia trachomatis: most common bacterial STD
    • –Obligate intracellular pathogen •Azithromycin •Doxycycline
  30. Intracellular Strategies
    • Escape: Richettsia
    • Prevent Fusion: Ehrlichia, Chlamydia
    • Phagolysosome survival: Coxiella
  31. Chlamydia
    • Obligate->Epithelial Cells
    • o Contains no peptidoglycan because it uses the host cell’s membrane
    • o Leads a Biphasic lifestyle
    • Elementary body (EB, infectious)
    • Reticulate body (RB, non-infectious)
    • o C. trachomatis
    •  Virulence Factors:
    • • Intracellular
    • • Preventing fusion of phagosomes with lysosomes
    •  Epidemiology:
    • • Most common bacterial STD in the US
    • • Can also be passed from mother to child during vaginal childbirth
    •  Diseases (Chlamydia): •Azithromycin •Doxycycline
    • Trachoma: Ocular infection
    • o World’s leading cause of infectious blindness
    • • Genital Infectionvery similar to gonorrhea in terms of clinical magnification
    •  Lab Diagnosis: Co-culture organism with monolayer of human epithelial cells
  32. Microbial Control (Sterilization and disinfection) Resistance
    • o Most Resistant: Prions, bacterial spores, mycobacteria
    • o Least Resistant: Viruses with lipid envelopes
  33. Sterilization:
    • ALL types of microorganisms, including spores, but NOT prions
    • o Autoclave: 121C at stream pressure of 15psi for 15-20 mins OR 134C at a stream pressure of 30psi for 3 minutes (flash cycle)
    • thermal coagulation of proteins
    • o Ethylene Oxide: Gas sterilization
    • Alkylating kills by damaging proteins and nucleic acids
    • explosive,carcinogenic,toxic
    • o Glutaraldehyde: “Cold sterilizeralkalizing agent
    • extremely toxic
    • Filtration: (physical) (.22 um, 20 nm virus)
    • Ionizing rays (x and gamma)
    • o Sterilization assurance:
    •  Spore Strip impregnated Bacillus spores
    •  Self-contained spore used in steam sterilizer
  34. Disinfection:
    • a lower grade process that kills or removes many microorganisms, excluding spores and prions (BLUE); used for destroying microorganisms in non-living objects, used on inanimate objects
    • o Alcohol: most widely used antiseptic, 70-95% alcohol required
    • Antiseptic: used to destroy microorganisms on living tissue, used on viable tissues
    • o Chlorine
    • o Formaldehyde: denatures proteins and nucleic acids
    • o Oxidizing agents: Chlorine Bleach, ozone, H2O2
  35. Pasteurization:
    • logarithmic reduction
    • not intended to kill all microorganisms, instead meant to achieve a “logarithmic reduction” in the number of viable organisms, thus reducing their number so they are unlikely to cause disease
    • milk heated then rapidly cooled
  36. What is a virus?
    • Structural Simplicity: viruses consist of nucleic acid (RNA or DNA, but never both), protein, (and lipid)
    • • Extracellular infectious viral particle is called a virion
    •  Intracellular Parasitism: viruses are obligate intracellular parasites that depend on the host cell machinery for replication
  37. Capsid Arrangements
  38. Virion structure and properties
    •  Virion: a complete physical entity that can exist extracellularly and can infect new host cells
    • • Composed of: the virus genome, protein capsid (helical, isosaheral or complex structure), and an envelope (or not)
    • o Capsid Symmetry: most economical ways to build a structure with subunits
    •  Two most common forms of capsid symmetry: helical and polyhedral (“sphereical”)
    •  One or multiple proteins in each subunit, like building blocks
  39. Naked Capsid:
    • stable to heat, acid, proteases, detergents, drying.
    • Released from cell by lysis
    • o Can be spread easily
    • o can dry out and retain infectivity
    • o can survive the adverse conditions of the gut
    • o Can be resistant to detergents and poor sewage treatment
    • o Antibody may be sufficient for immunoprotection
  40. Enveloped Virions:
    • made from a membrane of lipids, proteins, and glycoproteins,
    • labile to acid, detergents, drying and heat, released from cell by budding and cell lysis
    • o Must stay wet
    • o Can’t survive the GI tract, will destroy envelope and virus won’t be able to attach to its specific receptors
    • o Spreads in large amounts
    • o Does not need to kill the cell to spread
    • o May need antibody and cell-mediated immune response for protection and control
    • o Elicits hypersensitivity and inflammation to cause immunopathogenesis
  41. Single Step Growth Curve
    • enter, sythesize, assemble, burst w/ numbers
  42. Viral Replication
    • 1. Attachment- viral attachment proteins VAP/ host receptor ->tropism and host range
    • 2. Penetration-Endocytosis/Fusion or Injection
    • 3. Uncoating - of endosomal vesicle.
    • 4. Synthesis (synth viral mRNA, translate mRNA, replicate genome)
    • 5. Assembly-genome into capsid
    • 6. Release-Lysis, budding, exocytosis
  43. Enveloped Virions replication cycles:
    • • Attachment: Viral attachment proteins (VAPs) bind to cellular surface receptor (glycoprotein)
    • • Penetration: energy dependent process that sometimes involves translocation directly into the cytoplasm. Can also be pH dependent
  44. Capsid Virions replication cycles:
    • • Penetration: is mainly by endocytosis, pH dependent
    • 1. Enveloped virus can actually fuse with the cell membrane and inject its genetic material into the cell
    • 2. Capsid will be translocated into the cytoplasm and will dock with the nucleus to inject its DNA into the nucleus for replication and protein synthesis
    • 3. Endosome: the whole capsid/envelope is taken in and uncoated inside of the cell
    • 4. The entire cellular membrane engulfs the virus and due to the change in pH, causes lysis of the endosome and uncoating inside of the cytoplasm prior to the virus docking with the nucleus
    • 5. Once the virus gets into the cell, there is an eclipse where the proteins are assembled before they are released outside of the cell
    • a. The number of viruses that can be produced per replication cycle varies between virus types
  45. Types of viral infections
    • Abortive- fails to multiply
    • Latent-infection without virus production
    • Productive-virus production leading to cell death, lyse cells, cytotoxic proteins, inhibiction of normal synthesis, attack by immune responses.
  46. Fundamental properties for viral propagation
    •  All viral genomes are packaged inside particles that mediate their transmission from host to host
    •  The viral genome contains the information for initiating and completing an infectious cycle within a susceptible, permissive cell
    •  All viruses are able to establish themselves in a host population so that virus survival is ensured
  47. DNA Viruses Genetic Content
    • o Most DNA viruses are double stranded
    •  Enveloped: pox, herpes, hepadna
    •  Naked Capsid: polyoma, papilloma, adeno, parvo (ss)
    • o Genome replication:
    •  Small DNA viruses are replicated by host DNA polymerase (papilloma, polyoma)
    •  Large DNA viruses use their own replication machinery (herpes, pox)
    •  Steps:
    • • Attachment
    • • Penetration
    • • Uncoating
    • • Genome replication and gene expression
    • • Assembly
    • • Maturation
    • • Release
    • o Properties:
    •  DNA is not transient or labile
    •  Many DNA viruses establish persistent infections
    •  DNA genomes reside in the nucleus (except for pox)
    •  Viral DNA resembles host DNA for txn and replication
    •  Viral genes must interact with host txn machinery (except for pox)
    •  Viral gene txn is temporally regulated
    • • Early genes encode DNA-binding proteins and enzymes
    • • Late genes encode structural proteins
    •  DNA polymerases require a primer to replicate the viral genome
  48. Viral Pathogenesis
    • o Virulence Factors: any virally encoded activity that allows virus to cause disease
    • o Host factors: immune responses to control the infection
    • o Vaccine: loss of virulence factors and induction of immune responses. Vaccines can be live viruses or individual antigens
    • o Effect of viral replication on cells
    •  Non-permissive cells
    •  Semi-permissive cells
    •  Permissive cells: allow complete replication cycle for virus
    • o Effect of viral replication on tissue
    •  After multiplication, cell can die due to lysis, develop a persistent infection, or develop a latent infection (virus present, but not causing harm to cell, later emerges in lytic infection)
    •  Or, the cell can transform into a tumor cell that will eventually result in cancer
  49. Outcomes of a viral infection:
    • Abortive infection (virus fails to multiply usually due to mutation)
    • Lytic infection (virus production leading to cell death)
    • o Inhibition of cellular protein synthesis
    • o Inhibition of cellular nucleic acid synthesis
    • o Direct toxicity of viral products
    • o Expression of viral antigens on cell surface for immune attack
    • o Physical disruption of cell by accumulation of viral particles
    • o Apoptosis
    • o Syncytia formation: cell surface expression of viral proteins leads to cell to cell fusion
    • • Persistent infection (infection without cell death)
    • o Chronic: viral production and release ongoing without interfering with cellular metabolism
    • o Latent: usually when not all viral genes can be expressed and when conditions allow expression of remaining viral genes
    • o Transforming (oncogenesis)
    • o Recurrent (herpes)
  50. Progression of Viral Disease:
    • Acquisition: entry into the body
    • Initiation: of infection at a primary site
    • Incubation period: when the virus is amplified and may spread(via blood or cns) to a secondary site
    • • No symptoms, but still capable of passing the virus on to others
    • Replication: in the target tissue, which causes the characteristic disease signs
    • Immune Responses: that limit and contribute (immunopathogenesis) to the disease
    • Contagion: Virus production in a tissue that releases the virus to other people for contagion
    • Resolution or persistent infection/chronic disease:
  51. Determinants of Viral Pathogenesis:
    •  Interaction of virus with target tissue
    • • Access of virus to target tissue
    • o Specificity of viral attachment proteins
    • o Tissue-specific expression of receptors
    • • Stability of virus in the body (Temp, GI tract)
    • • Ability to cross the skin or mucous epithelial cells
    • • Ability to establish viremia (virus in the blood)
    • • Ability to spread through the reticuloendothelial system
    •  Cytopathologic activity of the virus
    •  Host protective responses
    • • Antigen-nonspecific innate immune responses
    • o Natural killer cells (activated by interferons, target and kill virus-infected cells), macrophages, dentritic cells
    • • Antigen-specific adaptive immune responses
    • o T-cell responses: CD4 (TH1 and TH2) and CD8 (cytotoxic lymphocytes)
    •  Immunopathology
    • • Interfereon: flu-like systemic symptoms
    • • T-cell responses: delayed-type hypersensitivity
    • • Antibody: complement, antibody-dependent cellular cytotoxicity, immune complexes
    • • Other inflammatory responses
  52. Viremia
    • Viruses in blood
  53. Patterns of Viral Infection
    • Acute-rapid resolution, elimination
    • Persistent Chronic-continual production, Latent, reactivating-periodic virus production
  54. Mechanisms for viral evasion of immune responses:
    • • Hidden from antibody:
    • o Latent infection, syncytia formation, antigenic variation, secretion of blocking antigen, decay of complement
    • • Inhibit immune cell functions:
    • o Impairment of dentritic cell function or lymphocyte function, prevention of CD8 T-cell killing, killing CD4 T cells and alteration of macrophages, suppression of NK, T and B cells, and immunosuppressive factors
    • • Decreased Antigen Presentation
    • o reduced class I MHC expression, inhibition of class I MHC transcription, blocking translocation to surface, blocking surface expression of B2-microglobulin and Class I MHC molecules, preventing peptide binding to class I MHC molecules
    • • Inhibition of Inflammation
    • o Blocking action of IL-1 of tumor necrosis factor
    • o Blocking production of interferon
    • o Blocking action of interfereon
    •  Inhibits up-regulation of MHC expression
    •  Blocks dsRNA activation of interferon-induced protein kinase (PKR)
  55. Viral transmission
    •  Modes of entry: usually through broken skin or any mucous membranes. Virus may replicate at primary site or may disseminate
    • • Respiratory transmission
    • • Fecal-oral transmission
    • • Contact (lesions, saliva, fomites)
    • • Zoonoses (animals, insects)
    • • Transmission via blood
    • • Sexual contact
    • • Maternal-neonatal transmission
    • • Genetic (prions, retroviruses)
    •  Tropism: preference for certain tissues
    •  Dissemination: may take place in stages an dthrough various routes
    • • Transported in blood (viremia)
    • • Through lymphatics or cells of immune system
    • • Neurons
  56. Viral oncogenesis
    • Contributing factor in 20% of human cancers
    • Activation of Proto-oncogenes
    • promote cell growth and inhibit death
    • mutations and over-expression
    • Inactivation of Tumor Suppressor genes
    • genes that repress cell growth and promote death
    • - by mutations and inhibition
    •  Studying viruses lead to two critical discoveries in tumor biology
    • • Discovery of oncogenes
    • • Discovery of tumor-suppressor genes
    •  Mechanisms of virus-induced neoplasia
    • • Indirect:
    • o Suppression of host immune system, impaired elimination of tumor cells
    • o Stimulation of cell proliferation, increased “targets” for other neoplastic changes
    •  Tissue regeneration after virus cytolysis
    •  Mitogenesis of immune competent or other cells
    • • Direct:
    • o “Hit and Run:” no crucial virus gene or structure whole persistence is essential
    •  Viral DNA or viral functions act transiently
    • o Crucial parts of viral genomes persist in tumor cells
    •  RNA tumor viruses
    • • Animal retroviruses as model systems
    • • Human T-cell leukemia virus
    • • Hepatitis C virus
    •  DNA tumor viruses
    • • Hepatitis B
    • • Polyoma
    • • Papilloma
    • • Adenovirus
    • • Epstein-Barr
    • • Human herpesvirus-8
  57. RNA tumor viruses
    • • Animal retroviruses as model systems
    • • Human T-cell leukemia virus
    • • Hepatitis C virus
  58. DNA tumor viruses
    • • Hepatitis B
    • • Polyoma
    • • Papilloma
    • • Adenovirus
    • • Epstein-Barr
    • • Human herpesvirus-8
  59. Smallpox (vaccine)
    • Smallpox – devastating and highly infectious diseases
    • ¤Inoculation (variolation)
    • subcutaneous introduction of materials from skin lesions of people with smallpox into unaffected individuals
    • ¤Cowpox
    • Dairymaids that had cowpox rarely got smallpox
    • ¤Edward Jenner (vaccination) Inoculated a boy with cowpox (vaccinia) and then later inoculated with smallpox -> no disease
    • - vaccination replaced variolation
  60. Vaccines
    • o Three basic types: live virus, inactivated virus, sub-unit vaccine
    • Live has most risk and immunogenicity (§MMR, Chickenpox, Nasal influenza)
    • Sub-unit is the most common and are just the surface proteins of the virus
    • o Administration: oral, subcutaneous or scarification, intramuscular
    • o Adjuvants: used to increase the immunogenicity of subunit vaccine and inactivated vaccine
    •  Enhance the immune response and are included in inactivated and subunit vaccines
  61. Diagnosis of viral infections
    • (Infectivity, Visualization, Detection, Evaluation)
    • o Infectivity (need live virus)
    •  Virus-induced cytopathic effects (CPE) on cells
    •  Incubate a sample with a cell line and use light microscopy to determine the effects
    • • Will sometimes see syncytia: multinuclear cell, fusion of multiple cells caused by the protein of paramyxoviruses (measles)
    • • Can see plaques: focal areas of cell destruction
    • • Hemadsorption: viruses that express hemagglutinin protein will bind red blood cells and cause them to attach to the culture.
    • o Influenza, mumps, parainfluenza
    •  Impractical and not very useful clinically
    • o Visualization with an electron microscope: can identify a virus using its shape and size
    • o Detection of viral components like proteins or genomes
    •  Viral proteins: use antibodies to detect capsid and glycoprotine
    • • Use an ELISA for viral protein detection with antibodies
    • • Western Blot/Immunofluorescence assay: using antibody against viral protein for detection
    • • Protein activity: use enzymatic activity of reverse transcriptase or neuraminidase for example to identify the virus
    •  Nucleic acids: need to sequence the DNA/RNA
    • • In situ hybridization
    • • Southern (DNA) or Northern (RNA) blots
    • • Amplification with PCR
    • o Evaluation of patient’s immune response (serology)
    •  Virus-specific antibody: indicates a past or recent infection or chronic infection
    •  Do blot, ELISA, IFA, hemagglutination inhibition assay, or neutralization with antibodies screening to determine if the patient is producing antibodies for the virus or not
    • • Neutralization: virus-specific antibody blocks the virus to infect cells, thus to inhibit CPE
    • • Hemagglutination Inhibition: virus-specific antibody blocks the virus to aggregate RBCs
  62. Summary of Detection methods:
    •  During disease stage (acute phase): choosing anti-viral therapy and deciding prevention
    • • PCR of viral nucleic acids
    • • ELISA of viral proteins
    •  During chronic infection or after resolution: blood screening and epidemiology studies
    • • Serological studies of virus-specific antibodies
  63. Anti-Viral Therapy
    •  Target: Any step of the viral replication cycle that is essential for viruses, but not our cells
    • • Attachment: neutralizing antibodies
    • • Uncoating: proteins that block the release of viral genomes by preventing uncoating
    • • Nucleic Acid Synthesis: most anti-viral drugs use this method
    • o Target specialized polymerases
    • o Use nucleoside analogues
    • • Protein Synthesis:
    • o Interferons (alpha and beta)
    •  Body’s natural responses to infection
    •  Actions:
    • • Degradation of viral mRNA
    • • Inhibition of protein synthesis
    • • Enhance host immune response
    •  Used to treat chronic HBV and HCV infections
    • • Assembly and release
    • o Protease inhibitor (HIV, assembly)
    • o Neuraminidase inhibitor (H1N1, release, Tmaiflu)
    •  Prevents the virus from being released from the cell surface
    •  Problems: use the host cell’s machinery and enzymes for replication
    •  Most common targets: virus encoded enzymes, structures of the virus
    • Target Virus
    • DNA Polymerase Herpesvirus
    • Reverse Transcriptase HIV, Hepatitis B
    • RNA polymerase RSV, Hepatitis C
  64. RNA Viruses
    • o +RNA: once the RNA genome gets into the cell, that RNA can be directly translated into protein
    • o –RNA: once the RNA genome gets into the cell, then need one round of NRA replication in order to be translated
    •  Must encode its own RNA polymerase to replicate the RNA from RNA
    • o dsRNA: can’t be translated, therefore must synthesize positive RNA first and then be translated into protein
    • o Retroviruses: first convert ssRNA into dsDNA using reverse transcriptase
    •  dsDNA can be integrated directly into the host cell’s DNA using viral integrase
    •  once it becomes part of the host cell’s genome, normal transcription and proteins are readily translated
  65. +RNA:
    once the RNA genome gets into the cell, that RNA can be directly translated into protein
  66. –RNA:
    • once the RNA genome gets into the cell, then need one round of NRA replication in order to be translated
    •  Must encode its own RNA polymerase to replicate the RNA from RNA
  67. dsRNA:
    can’t be translated, therefore must synthesize positive RNA first and then be translated into protein
  68. Retroviruses:
    • first convert ssRNA into dsDNA using reverse transcriptase
    •  dsDNA can be integrated directly into the host cell’s DNA using viral integrase
    •  once it becomes part of the host cell’s genome, normal transcription and proteins are readily translated
  69. RNA Virus Translation:
    • Three options for protein processing
    •  Make the first protein per RNA
    •  Make a large protein and chop it up into individual proteins
    •  Make a smaller RNA from the large RNA (subgenomic RNA)
  70. RNA Virus Evolution:
    •  RNA polymerase lacks a proof-reading mechanism and incurs about 1/10,000 mismatches
    • • This is very important because it creates diversity among RNA viruses and also explains the rapid evolution and emergence of drug resistant strains
  71. +RNA Viruses
    • o Non-Enveloped Viruses
    •  Picornavirus: IRES
    • • 1st cause of common cold
    •  Norovirus: gastroenteritis
    • o Enveloped Viruses
    •  Togavirus/Flavivirus:
    • • Arboviruses: WNV, DV, YFV
    • • HCV, Rubella (human hosts without vector)
    •  Coronavirus
    • • 2nd cause of the common cold
    • • SARS
  72. –RNA Viruses
    • o Non-Segmented Viruses
    •  Paramyxovirus (F-syncytia)
    • • Measles, mumps, Respiratory Syncytial virus
    •  Rhadbdovirus (Animal Bites)
    • • Rabies
    •  Filovirus
    • • Ebola, Marburg
    • o Segmented Viruses (Reassortment)
    •  Arenavirus (rodent reservoirs)
    •  Bunyavirus (most are arboviruses)
    •  Orthomyxovirus (replication in nucleus)
    • • Influenza Virus
  73. Encephalitis (viral causes):
    •  Picornaviruses
    • • Poliovirus
    • • Enterovirus 71
    •  Togavirus
    • • Equine Encephalitis
    •  Flavivirus
    • • West Nile Virus
    •  Rhabdovirus
    •  Arenavirus
    • • Lymphocytic choriomeningitis virus
    •  Bunyavirus
  74. Common Cold (viral causes):
    •  Picornavirus
    • • Rhinovirus (1st)
    •  Coronavirus (2nd)
  75. Gastroenteritis (viral causes):
    •  Norovirus
    •  Reovirus
    • • Rotavirus
  76. Hemorrahagic Fever (viral causes):
    •  Flavivirus
    • • Dengue Virus
    • • Yellow Fever Virus
    •  Filovirus
    • • Ebola and Marburg Viruses
    •  Arenavirus
    • • Lass Fever Virus
    •  Bunyavirus
    •  Orthomyxovirus
    • • Hantavirus
  77. Fungi and Parasites General Features:
    • o Yeast: oval to round shape
    • o Hyphae: elongated tubular structures, may have septae (partition)
    • o Mycelium (Mold): a mass of hyphae
    • o Pseudohyphae: elongated budding cells that have not separated
    • o Condidia: specialized spore-like structures of various shapes produced by hyphae
    • o Arthroconidia are produced by direct break up of hyphae
    • o Dimorphism: fungus existing in two different forms depending on condition
  78. Fungi and Parasites Cellular Features
    • o They are eukaryotes
    • o Nuclei are divided into chromosomes
    • o Cytosol contains organelles such as mitochondria, ribosomes, Golgi apparatus, ER
    • o Plasma membrane contains sterols
    • o Cell wall contains complex polysaccharides
    • o Lack chlorophyll
    • o Best stained with:
    • o Periodic acid Schiff (PAS)
    • o Methenamine silver
    • o Calcofluor
  79. Fungi and Parasites Pathogenesis
    • 1. Direct invasion of tissues: hyphae invade blood vessels and cut off oxygen/blood supply to the tissue
    • 2. Toxin production
    • 3. Hypersensitivity reaction: cause asthma-like immune reaction in the lung (allergy)
  80. Superficial and Cutaneous Mycoses (Fungi)
    • o Dermatophytes: three genera
    • o Microsporum, Trichophyton, Epidermophyton
    • o Can involve skin, nail or hair only because they don’t invade tissue
    • o Epidemiology: Anthropophilic, zoophilic, geophilic
    • o Lesions on skin are called tinea (ringworm) and specified along area of involvement (ex/ tinea capitis=hair and scalp
    • KOH prep skin scrapings
  81. Systemic Mycoses (Fungi)
    • o Some are endemic (only present in certain areas) and infect normal hosts who are usually asymptomatic
    • o Usually acquired through inhalation of conidia or arthroconidia
    • Histoplasma Capsulatum
    • Coccidioides Immitis
    • Crytococcus Neoformans
    • Candidiasis
    • Aspergillosis
    • Zygomycosis
    • Pneumocystis Jiroveci
  82. Histoplasma Capsulatum
    • o Characteristics:
    •  Grown as a mold (hyphae) or as microconidia (inhaled)
    •  In humans it converts to yeast form
    •  Macrophages appear to be initial target
    •  Can reactivate many years later
    • o Epidemiology:
    •  Present in US Midwest along Ohio and Mississippi rivers
    • o Clinical Syndromes
    •  Most infected people are asymptomatic except the immunocompromised
    •  Can disseminate to mucous membranes including the mouth
    • o Lab diagnosis
    • Polysaccharide antigen detection in serum and urine
  83. Coccidioides Immitis
    • o Characteristics: Formal Dimorphism
    •  In nature hyphae form arthroconidia which is inhaled
    •  Turns into Spherule: large sack with double refractile wall that is filled with endospores
    • o Epidemiology
    •  Southwestern US and Bakersfield
    •  Immunogenetics plays a role, large differences in ethnic groups
    • o Clinical Syndromes
    •  Most cases are asymptomatic or have mild “flu-like” symptoms
    •  Pulmonar complications
    •  Dissemination to skin, bones and CNS(encephalitis)
    • o Lab diagnosis:
    •  Spherule in tissue
  84. Crytococcus Neoformans
    • o Characteristics
    •  NOT dimorphic, always in yeast-form shape
    •  Polysaccharide capsule important in pathogenesis
    • o Clinical Syndromes
    •  Initial infection is pulmonary, dissemination to skin and brain
    •  Common cause of meningitis in HIV patients
    • o Lab Diagnosis:
    •  India Ink, polysaccharide antigen is most useful
    • usually requires therapy
  85. Candidiasis
    • o Characteristics:
    • Polymorphic, yeast form when cultured, but in tissues could be hyphae and pseudohyphae
    •  Part of endogenous flora
    •  Can be sexually transmitted
    •  Candidiasis Albicans is the most common species
    • o Clinical Syndromes
    •  Has predilection for skin, mucous membranes but can disseminate
    •  After bacteria, the most important poathogen in immunocompromised patients (#4 pathogen found in human blood in the US)
    • o Host Factors:
    •  Variety of conditions including: pregnancy, trauma to skin and mucous membranes, surgery, diabetes, malnutrition, malignancies, immunodeficiences, chemotherapy, antibiotics
  86. Aspergillosis
    • o Characteristics
    •  Mold with conidia, very ubiquitous in nature
    •  Bread mold
    • o Clinical Syndromes
    •  Allergic reaction in lungs
    •  Invasive disease: hyphae invade along blood vessels causing necrosis
    •  Toxins: aflatoxin produced by A. flavus, very potent carcinogen associated with liver cancer
    • o Host factors:
    •  Almost always involves immunocomproised host
    • Lab test:
    • biopsy, serology, Galactomannan
  87. Zygomycosis
    • o Characteristics
    •  Hyphae invade along blood vessels causing necrosis
    • o Clinical Syndromes
    •  Invasive form especially in lungs in neutropenic patients (those lacking neutrophils)
    •  Rhinocerebral form: almost exclusively seen in diabetics out of control
  88. Mucormycosis
    • Characteristics:
    • 1. moulds, genera: Mucorales, Rhizopus
    • 2. hyphae along vessels (OMFS)
    • Clinical:
    • 1. lungs (neutropenic pts)
    • 2. Rhinocerebral form-diabetics
  89. Pneumocystis Jiroveci
    • o Characteristics
    •  rRNA analysis indicates that most likely it is an atypical fungus
    • • cholesterol not ergosterol in cell membrane
    • • exists in trophozoite and cyst forms
    • • responds to antiprotozoal, but not antifungal drugs
    •  probably acquired from environment (inhalation)
    •  Reactivates when opportunity arises (AIDS pneumonia)
    • Dx: staining, no culture
  90. Parasites General Features:
    • o eukaryotic
    • o Can be multicellular or unicellular
    • o Helminths (worms) are divided into flat worms (tapeworms and flukes) and round worms (nematodes)
    • o Can have complicated life cycles involving more than one host
    • o Humans can be definitive host (harboring adult or sexual form) or intermediate host (harboring larval or asexual stage)
    • o As a group globally they are among the most important causes of human infection
  91. Entamoeba Histolytica
    • Protozoa
    • o Trophozoites: form causes clinical infection, does not survive in environment and therefore not infectious
    • o Cyst: infectious form
    • o Tx: oral-fecal route, poor sanitation especially in water
    • o Causes intestinal (diarrhea) and extraintestinal diseases (liver, lung or brain abscess)
  92. Malaria
    • Protozoa
    • o Caused by one of four Plasmodium species
    • P. falciparum: most dangerous
    • P. vivax: most common
    • P. malariae & ovale
    • o Tx: mosquitoes (anopheles)
    • o Complex life cycles involving liver, erythrocytes and mosquito (sporozoites is the infectious form)
    • Malaria (lungs or brain hemmorage)
    • Dx: peripheral blood smear, RDT(rapid diagnostic)
    • some anti-malarial resistance
  93. Trichomonas vaginalis
    • Protozoa
    • o Trophozoite form only, can’t survive outside of host
    • o Sexually transmitted
    • o Most men are asymptomatic, women are symptomatic
  94. Toxoplasma Gondii
    • Protozoa
    • o Humans (intermediate hosts) usually acquire oocysts from cat (definitive host) feces or undercooked infected meat
    • o Can cause severe damage to fetus in utero and brain abscess in AIDS patients
  95. Leishmania
    • Protozoa
    • o Tx: sandflies
    • o Depending on species, patient may have deep organ invasion(L. donovani)(spleen & liver)
    • cutaneous (L. tropica)
    • mucocutaneous (L. braziliensis)
  96. Trypanosomes
    • Protozoa
    • o T. brucei: transmitted by Tsetse fly and causes African “sleeping sickness”
    • o T. cruzi: transmitted by Reduviid bugs (Kissing bugs) and causes American trypanosomiasis
  97. Enterobius Vermicularis (Pinworm)
    • Nematodes (Roundworms)
    • o Most common helminth infection in US
    • o Transmitted person-to-person through clothing, inhaling infested dust, autoinfection
    • o Worms migrate out of rectum at night causing perianal and vaginal itching
    • o Diagnosed by “scotch tape” test revealing eggs, occasionally worms can be seen
  98. Ascaris Lumbricoides
    • Nematodes (Roundworms)
    • o Infects about 1 billion people every year
    • o Acquired through ingestion of eggs from focally contaminated food, dirty fingers, fomites
    • o Eggs develop into larva and penetrate intestinal wall, carried to lungs, carried out of lungs by bronchial mucus, swallowed and grow into adults (23-35cm long) in the intestines.
    • o Can cause occasional pneumonia, abdominal pain, diarrhea, intestinal obstruction
    • o Eggs easily found in stool as an adult female produces up to 200,000 eggs per day
  99. Strongyloides Stercoralis
    • Nematodes (Roundworms)
    • o Migrating larva can cause pulmonary infiltrates and wheezing
    • o Hyperinfection: large number of defective larvae penetrating intestine and allow bacteria to get in, leading to severe bloody diarrhea
    • o Dissemination: migrating larvae invading organs, immnocompromised patient at risk
    • Dx: LARVAE not eggs in stool
  100. Trichinosis Spiralis
    • Nematodes (Roundworms)
    • o Acquired by ingesting encysted larvae in undercooked pork then encapsulate in skeletal muscle
    • o Initial diarrhea and vomiting followed about a week later by fever, muscle pain, periorbital edema, high eosinophilia
    • Dx: muscle biopsy
  101. Schistosomes
    • Trematodes (Flukes)
    • o Cercaria invade skin, enter circulation, grow into adult forms which mate, produce a lot of eggs
    • o Reaction to eggs cause most problems to host
    • o Can cause intestinal and liver disease as well as urinary bladder problems
    • Nile river in Egypt
  102. Cestodes (Tapeworms)
    • Trematodes (Flukes)
    • o Taenia Solium
    • o Pork tapeworm, acquired by eating undercooked pork
    • o Can cause either tapeworm in intestine with few symptoms or cysticercosis (intermediate form of disease, dissemination to eyes, brains, lungs, most common cause of seizures in people from Mexico)
    • o Fecal-oral route
  103. Diphyllobothrium Latum
    • Trematodes (Flukes)
    • o Fish tapeworm: acquired from fresh crustaceans and fish
    • o Causes B12 deficiency