MedMicroTestA

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BigMig
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37348
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MedMicroTestA
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2010-09-26 22:29:16
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Med micro
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Med micro
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  1. Pathology
    The study and functional changes in cells, tissues, and organs underlying
  2. Pathophysiology
    Changes in the physiological factors that underlie states
  3. Cell Envelope
    • Cytoplasmic membrane
    • cell wall
    • S-Layer
  4. Processes
    Virulence, Etiology, Pathogenesis, Morphological changes, Clinical significance
  5. Cell Wall
    • External to cyto membrane
    • = murein+ outer membrane + Brausn lipoprotein
  6. Cell Membrane
    • = cytoplasmic membrane
    • Bacterial membranes have hopanoids, not sterols
  7. Peptidoglycan
    • Gives cell rigidity
    • Consists of alternating units of two modified sugars (NAM & NAG)
    • Chains are cross-linked btw NAM units
  8. gram POSITIVE
    • Single thick layer - Peptidoglycan
    • Teichoic acids
    • Lipoteichoic acids
    • NO OUTER MEMBRANE
  9. Gram NEGATIVE
    • Multi-layered, complex
    • Thin layer peptid- btw 2 lipid bilayers
    • No teichoic acids
    • Outer membranes (Phospholipid bilayer, LPS, Proteins)
    • LPS (Lipid A, Antigen O, Polysaccharide structure)
  10. S-Layer (Crystalline surface layer)
    • Arrangement (Ext to Peptid- or OM, Archea only layer ext)
    • Consist of protein subunits (protein/glyco-, tetrahedral/hexagonal)
    • Functions (Adhesion, Maintains cell morpholgy, Phage receptor)
  11. Reasons to care about bacterial cell structure
    • Point of attack for most abundant drugs
    • Imparts virulence factors
    • Mechanisms of identification for bacteria
  12. Proteins of Bacterial Cytoskeleton
    FtsZ, MreB, CreS
  13. Glycocalyx
    • Extracellular polymeric material
    • Capsule, slime layer
    • Functions - Attachment to substrate, host, other cells; Protection of cell from host, desiccation, viruses, toxins
  14. Capsule
    • well-organized, not easily removed, exludes particles
    • Streptococcus, Bacillus, N. Meningitdus, Klebsiella
  15. Slime Layer
    • Diffuse
    • Easily removed
    • Pseudomonas
  16. Flagella
    • Long thin proties on appendages
    • 20nm wide
  17. Flagella Types
    • Monotrichous - 1 hair
    • Amph - both/either
    • Lopho - tuft
    • Hairy - Salmonella, E. coli
  18. Fimbriae & Pili
    • Shorter than flagella
    • Similar structure
    • Few/cells (1-10)
    • Functions (Vertical transfer)
  19. Types of Vertical Transfer
    Conjugation, Transduction, Transformation
  20. Endospore Structure
    • Exporoium (thin) [outer, inner, undercoat]
    • Spore coat (thick protein)
    • Cortex (peptide-, dipicolonic acid, Ca++)
    • Core
  21. Endospore structure (Cortex)
    • Situated btw outer and inner forespore membranes
    • Membranes often continuous with core on electron micrograph
    • Peptidoglycan, dipicolinic acid, Ca++
  22. Endospores
    • Dehydrated layered structure allowing suspended animation of bacteria
    • Formed inside some gram-positive bacteria
    • Resistant to heat, radiation, acids, desiccation, UV
    • Contains copy of chromosomes
    • Position of spore in cell used for identification
    • Produced by Bacillus and Clostridium
  23. Endospore Core
    • DNA in A form & bound to small acid-soluble proteins (SASP)
    • Core cytoplasm only 10 - 25% water, gel-like
    • Ca-diplocolinate but no PG
    • pH ~ 5.5 - 6.0
    • Also has ribosomes
  24. Stages of Endospore
    • Vegetative cell - Stage 0 (DNA becomes dense)
    • Stage II - Asymmetric cell division
    • Stage III - Mother engulfs forespore
    • Stage IV - Cortex Forms
    • Stage V - Protein coat surrounds forespore
    • Stage VI - Completion of coat (Dipicolinate)
    • Stage VII - Lysis of mother cell to release dormant spores (Different sigma factors and 100+ genes reqd)
  25. Colonization
    • Microbes able to multiply at site
    • no interference with normal function
  26. Infection
    = Successful attachment of microbe that may cause damage to the body
  27. Disease
    Process in which host-microbe interaction leads to alteration of structure of function, causing signs and symptoms
  28. Symbiotic Relationships
    • Commensalism
    • Mutualism
    • Parasitism
  29. Commensalism
    • One benefits, others indifferent
    • Corynebacterium spp
  30. Mutualsim
    Both partners benefit, E. coli
  31. Parasitism
    • One organism benefits at the expense of another
    • Vibrio spp (Necrotizing Fascitis)
  32. Est of Normal Flora
    • Fetus in utero lives in sterile environment
    • Upon vaginal delivery, exposure
    • Colonization 24-48 hr post-natal
    • Colonization means established growth on/within host
  33. Importance of Normal Flora
    • Prevent attachment of invaders
    • Deplete essential nutrients
    • Produce antimicrobial substances (Bacteriocins, Produce toxic metabolites)
    • Stimulate
  34. Skin Flora
    Staph epi, Prop acnes,Clos perf, Acinto Cac, Staph a, Carynem spp, Kocuria spp, Fungi (Candida, Malassezia)
  35. Propionibacterium acnes
    • Gram +, pleomorphic branching
    • may appear diptheroid
    • Most common anaerobic rod found in clinical specimens
    • Catalase (+) Positive
  36. Acinetobacter spp
    • Gram (-), bacilli, pleomorphic - coccobacilli
    • may grow in pairs, do not ferment cabs, Do not reduce to nitrates
    • Facultative intracellular organisms
    • Oxidase (-) Negative
    • Some Citrate (+) Positive
    • Contaminate resp. therapy equipment, pillows, catheters
    • Resistant to many antibiotics (Aminoglycosides + imipenem)
  37. Species of Acinetobacter on the skin
    • A. baumannii
    • A. calcoaceticus
    • A. lwoffi
  38. Normal Flora of Mouth and Pharynx
    • Streptococcus mutans, Srtreptococcus Sanguis, Viridans group
    • Plaque = biofilm on teeth
    • Progression: Strep -> Actinomyces isralli -> Veillonella -> Neissaria, Fusobacteria
    • Tooth surface microbes differ from saliva and mucosa due to redox potential
  39. Normal Oral Flora
    • Nasopharynx - Haemophilus sp
    • Anaerobes predominate in oral cavity
    • Peptostreptococcus, Bacteroides, Prevotella, Fusobacterium, Treponema, Capnocytophaga, Eikenella
  40. Normal flora in EYE and EAR
    • S. epidermis
    • Debate on whether eye has indigenous microbiota or just transients
    • Eye may have nasopharynx flora (Viridians, Haemophilus, Neisseria)
  41. Respiratory Tract Normal Flora
    • Normally sterile
    • Sterility impeded by trauma, iatrogenic methods
  42. Stomach Normal Flora
    Lactobacillus, Streptococcus, Heliobacter pylori
  43. Small Intestine Normal Flora
    • Anaerobes
    • Peptostreptococcus, Prevotella, Candida, Enterococci
  44. Large Intestine Normal Flora
    bacteroides, Fusobacterium, Peptostreptococcus, Enterococcus, E coli
  45. Bacteroides
    • Gram (-) anaerobe, non-pigmented, non-motile, capsulated
    • Most common anaerobe in GI tract
    • Usually not seen in infections above waist
    • B. vulgatisB. fragilis
    • Most anaerobe in bactericemia, Most common anaerobe in intrabdominal disease, grows in 20% bile
  46. GU Tract Normal Flora
    • Usually sterile in both sexes
    • Only urethra and vagina colonized
    • Lactobacilli
    • Staph Epi (catalase pos, coagulasse neg)
    • Viridans group
    • Fusobacterium - anaerobes
    • Candida albicans
    • Ureaplasma
    • Other Gram (+) anaerobic cocci
  47. Innate
    • Nonspecific internal defenses
    • First line of defense
    • Consist of phys barriers, complement, cytokines, inflammations, receptor proteins
    • NOT specifically directed to invading agent
    • Responses not affected by prior exposure
    • Operates constantly
    • no memory
    • Usually recognizes HOST
  48. Types of Nonspecific/Innate Immunity
    • Skin, epithelium
    • Physical action
    • Fever
    • Inflammation
    • Phagocytosis Antimicrobial activity
    • Changes in Fe+ availability
    • Complement
    • Toll-like receptors
    • Phagosome, Phagolysosome
  49. Natural Killer Cells
    • Large granular lymphocytes
    • No T cells receptors (TCR), immunoglobulin (Ig) molecules, or CD3 on surface
    • Destroy tumor cells and cells infected by some viruses
    • Sees every cell as target unless it detects a signal from that cell
    • Express CD16 receptor
    • NK cells look for MHC Class I molecule
    • Destroys these cells = Antibody Dependent Cell-mediated Cytotoxicity
    • No memory, Thus part of the innate
    • NK cells also involve interaction of FasL of NK cell with Fas protein (CD95) on target cell
  50. Toll-Like Receptors
    • Part of Innate System
    • Drosophilia
    • Recognize PAMPs
    • PAMPs bind CD36 or CD14
  51. Types of TLRs
    • LPS - TLR 4
    • Flagellin 0 5
    • dsRNA - 3
    • ssRNA - 8,7
    • CpG DNA 9
  52. Signal Transduction
    • Pamps bind to TLR
    • Leads to signals sent to activate transcription factors
    • Stimulates production of NF-kB (Cytokine Production) and IRF-3 (Stimulates Type 1 IFN)
  53. Complement
    • 26 proteins; Cascade activation
    • Alternate, Classical, Lectin
    • Opsonization, Lysis of cell membranes
  54. Activation of Complement:
    Alternate
    Classical
    Lectin
    • Activation on microbial surfaces
    • Fc portion of antibody (Ab) binds microbe surface
    • Plasmas protein binds mannose on microbe surface glycoproteins
  55. Adaptive
    • Antigen specific
    • Memory response
    • Involved in two lymphocyte types
    • Humoral B-ly secrete Ab; Cell-mediated T-ly activate macrophages
    • Includes lymphoctyes and antibodies
  56. Th1
    Cells produce cytokines that support inflammation and cell-mediated responses
  57. Th2
    • Cells stimulate eosinophils activation
    • Assist B ly
    • Promote production of IgM & IgG
    • support allergic reactions
  58. B cells
    Antibody response
  59. Signal Transduction
    • TCR (T cell Receptor) interacts with MHC-peptide-Ag-Complex
    • PIP2 -> DAG (Protein Kinases)
    • Activation of PKC
    • Phosphorylation of several proteins
    • Activation of various transcription factors including NF-kB
    • Genes activated in nucleus
  60. Cytokines
    • regulate cellular responses through binging
    • Innate adn Adaptive
    • Greater then or less then 30 kDa
    • Interferon - Isaac and Lindemann
    • Purified - Pestka
    • 1st Described - Nagano & Kojima
    • Stimulate production of C-reactive protein
    • CRP forms pentamer, and binds complement C3 to convert it to C3b
    • Inflammation triggers increased CRP
  61. 4 families of Cytokines
    • Hematopoietin
    • interferon
    • Chemokine
    • tumor Necrosis
  62. Types of Cytokines
    • IL - 1, 2, 4, 6, 10, 12, 23
    • TGF - Beta
    • TNF - Alpha
  63. Phagocyte
    • MEN
    • Macorphage
    • Eosinophil
    • Neutrophil
  64. Phagocyte Response
    • Attachment
    • Ingestion
    • Fusion to form phagolysosome
    • Killing in Phagolysosome
    • Digestion
  65. Inflammatory Process
    • Microbe penetrates barrier
    • Capillary Dilation (C3a and C5a)
    • Cytokine release
    • increased Heat and Blood flow
    • Edema and Pain
    • Diapedesis of leukocytes to injury site
  66. Diapedesis
    • Rolling adhesion
    • tight binding
    • diapedesis (squeeze btw endothelial cells)
    • Migration
  67. Antibodies
    • (2) Heavy chain, Light Chain(Kappa Lambda)
    • Variable and constant region
  68. 5 types of antibody Heavy CHains
    Mu, Delta, Gamma, Epsilon, and Alpha
  69. Major Histocompatibility Complex (MHC)
    • membrane-bound glycoproteins
    • Process and present Ag by T-ly
    • Self and non-self
    • Highly polymorphic gene loci
    • Located on chrom 6
  70. Class I MHC
    Found on all human cells except RBCs
  71. Class II MHC
    • Found on macrophages, dendritic cells
    • Present Ag to Naive T cells, B cell
  72. Responses to Viral Infections
    • cell-mediated (Th1 -> IFN-y, IL-2, TNF)
    • IL-2 & IFN activate NK and CD16 receptor
    • Cytotoxic T ly then specifically kill infected cells
    • Abs neutralize Viruses
    • slgA prevents viral attachment (stimulate complement)
    • Innate responds to interferons
  73. Interferon Innate Response (Signal Transduction)
    • dsRNA detected by Toll-like cell receptors
    • Induce IFN-alpha and beta
    • Activates 2' - 5' Oligoadenylate synthase
    • Causes activation of RNAase L
  74. Mechanisms towards bacteria
    • Ab neutralizes toxins
    • C' lyses bacteria
    • Ab + C' split C3b - Causing opsonization
    • C3a & C5a causes mast cells to degranulate
    • macrophage & neutrophil chemotaxis - proteins (toxins0
  75. Mechanisms towards Helminths
    • Humoral Component (IgE, IgG)
    • Cell-mediated component (ADCC) (Cytokines - IL-4,5,3)
  76. Mechanisms vs Fungi
    • Innate Immunity (Phagocytosis) (Alt & Lectin pathways of C')
    • Cell mediated (T cells)
  77. Active Immunization
    • Stimulation of immune response t challenge with immunogen
    • Natural through disease
    • Admin by health care worker (Artificial)
  78. Type of Passive Immunization
    • Transfer of performed Ab to recipient
    • Given for post-exposure prophylaxis
    • Poisonous snake and insect bites
    • Risk of type 3 hypersensitivity
  79. Transfer of performed Ab to recipient
    • Includes IgG fraction from plasma of donors
    • Natural across placenta
    • Injection of purified Ab or serum
    • Rapid temporary protection
  80. Post-exposure prophylaxis
    • Botulism
    • Tetanus
    • Diptheria
    • Hepatitis A &B
    • Measles
    • Rabies
  81. Type 1 Hypersensitivity
    • Immediate Hypersensitivity
    • Systemic Anaphylaxis
  82. Type 2 Hypersensitivity
    • Ab-mediated disease
    • ADCC
    • Cytotoxic cells with Fc receptors to Ab on target
    • Transfusions (Hemolytic disease of the newborn) (Drug induced hemolytic anemia)
  83. Type III Hypersensitivity
    • Immune mediated
    • Ags in excess
    • Results in large and small Ag-Ab complexes
    • Small IgG aggregates from immune responses dont fix C'
  84. Type IV Hypersensitivity
    • T cell mediated Ag must be present in context of a MHC class II molecule
    • Activated T cells are CD4+TH1 subtype
    • T(DTH) is a subset of TH1
    • MACs are recruited
    • Granulomas
  85. Granulomas Diseases
    • Tuberculosis - mycobacterim tubercolsis
    • Leprosy - mycobacterium lepra
    • Schistosmiasis
    • Sarcoidosis
    • Crohn Disease
  86. Attenuated Vaccine
    • Live but not pathogenic
    • Trigger cell mediated response
    • Gives herd immunity
  87. Inactivated Vaccines
    • Whole Agent
    • Subunit Both require booster doses
    • no Herd immunity
  88. Type of Live Vaccines
    MMR, Oral Sabin polio, VZV, Tellow Fever, BCG, Francisella
  89. Live Vaccines Characteristics
    • Result in undetectable diseases
    • Long-lasting immunity
    • Cannot cause disease
  90. Inactivated (Killed) Vaccines
    • Not life long
    • Humoral, not cell mediated
    • No local IgA response
    • Requires booster shots
    • Large doses
  91. Types of inactivated vaccines
    • Toxoid
    • Killed
    • Capsule protein subunit usually given with adjuvant
  92. Types of adjuvants
    • Alum
    • Cell wall components
    • Fruends Complete
  93. Types of Killed Vaccines
    • Killed
    • subunit
    • Peptide/polysaccharide
    • Toxoid
  94. Killed Vaccines
    Anthrax, Cholera, Salk polio, Pertussis, Rabies, Influenza
  95. Subunit Vaccines
    hep B
  96. Peptide/polysaccharide Vaccine
    • HiB,
    • Pneumococcus
    • Meninggococcus
    • HPV
  97. Toxoid Vaccine
    • Diphtheria
    • Tetanus
  98. Gardasil
    • Women 9-26 y/o before sexual activity
    • HPV serotypes 6, 11, 16, 18
    • Protein subunits produced from gen-engineered microbe
  99. NO vaccine available
    HIV, Herpes, Syphilus, Malaria, Cold Viruses, Hep C, Strep pyro, Flu
  100. Sites of Antibiotic Activity
    • Cell wall synthesis (PEP-, Mycolic acid)
    • 30s and 50s ribosomes
    • Involves metabolites not seen in eukaryotes
  101. Beta-Lactamases - Places of drug action
    • Inhibit Penicillin-binding proteins
    • PBPs can no longer catalyze transpeptidase reaction
    • Weakened cell wall
    • Vanco- binds terminal D-ala-D-ala of pentapeptides
    • Cross link btw NAM
  102. Cepha- vs Pen
    • Differ by R groups attached to Beta-lactam Ring
    • Pen - 1 R group
    • Ceph - 2R groups
  103. Aminoglycosides
    Block the initiation of translocation and causes the misreading of mRNA
  104. Tertracycline
    Blocs attachment of tRNA to the ribosome
  105. Streptogramins
    Each interferes with a distinct step of protein synthesis
  106. Macrolides
    Prevent the continuation of protein synthesis
  107. Chloramphenicol
    Prevents peptide bonds from being formed
  108. Lincosamides
    Prevents the continuation of protein synthesis
  109. Oxazolidinones
    Interfere with the initiation of protein synthesis
  110. Resistance - Mechanisms
    • Decrease uptake (Alter membrane Perm)
    • Drug-activating enzymes (Penicillinase)
    • modify drug targets
    • Increase export (Efflux pumps)
    • Horizontal s Vertical Evolution (qnrA and qnrB)
  111. Sulfonamides
    Competitive inhibitor of para-aminobenzoate
  112. Trimethoprim
    Inhibits dihydrofolate reductase
  113. Minimum inhibitory Concentration (MIC)
    Lowest conc of drugs that prevents growth of organism in vitro
  114. Minimum Bactericidal Concentration (MBC)
    Lowest concentration that kills 99.9% bacteria
  115. Tigecycline
    • Recently approved in US, Europe, UK
    • Potent vs Tet-R bacteria
    • Broad spectrum, Bacteriostatic, IV use
    • More resitant vs ribosomal protection and active efflux
    • use vs intra-abdominal and soft tissue infections
    • use for MRSA, Pen-R Pneumococcus, VRE
  116. Pleuromutilins
    Interact at 50 ribo subunit in PTC at A and P sites
  117. Daptomycin (Cubicin)
    • Lipopeptide (Sim to Glycopep- such as vanc-)
    • Use vs Gm+ cocci (Enodcarditis-right of heart, MRSA)
  118. Carbepenems
    Doripenems (Phase III) - Pseudomonas
  119. Cephalosporins
    Ceftobiprole (PhaseIII) - PBP2a in MRSA
  120. Glycopeptides
    Three Agents for treating complicated skin / skin structure infections (cSSSI)
  121. Dihydrofolate reductase inhibitor
    iclapri (Phase III) - csSSSI

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