How to against pathogens

Inactivated toxin used in a vaccine. injected to stimulate the production of antitoxins and provide immunity.

How to against pathogens

• Vaccin
  • Dead antigens
    • treatment
      • inactivation
        • heat, formaldehyde or gamma irradiation
      • Recombinant
        • peptide
          • may discrete portion (domain) of a surface protein as Vaccine
            • each domains as an epitope
        • Subunit
    • benifits
      • Safe
      • Cheaper
        • both production and storage
    • weakness
      • number and specificity of antigen is usually not enough
        • They can't multiply
        • an antigen may not good enough as pathogen with full epitopes
          • also the antigen might be damaged
        • requires periotic boost
        • only stimulates partially B cells' clonal expansion
      • still have risk to contain un-Inactivated microbes
    • Cases
      • Toxoids
        • Inactivated toxin used in a vaccine. injected to stimulate the production of antitoxins and provide immunity.
        • antitoxin are antibodies against exotoxin
          • Vaccine can be made by inactivated exotoxin
            • heat, formalin or phenol
      • Inacivated virus
        • seed stock influenza virus in embryonic hens eggs
          • subcutaneous injection
      • Subunit(component) Vaccine
        • detergent treated then centrifuged envoloped viruses
          • ex. influenza virus
            • get rid of HA & NA
        • empty envolope
          • HBV
      • subcellular fragments
      • surface antigens
  • Live attenuated pathogens
    • Attenuation methods
      • lower the applied dose than infectious doses
      • grow pathogen in foreign host such as animals, embryonated eggs or tissue culture
      • Recombinat DNA
        • inserts genome of dangerous virus into genomes of some harmless virus (vector)
          • Safe for vector storage
          • less risk for damage, but higher cost to design
      • DNA vaccine
        • Ingect DNA genes for antigen along into muscle as vaccine
          • easy to design, prepare, storage and specific trageting
            • can elicit T cell immunity
          • risks for mutagenesis, allergy, and immunlogical tolerance
    • benifits
      • stimulates whole memorable adaptive immune response
        • including T cell immunity
      • inject one time in small amount, no needs for multiple booster.
        • orally possible
    • weakness
      • High risk, attenuation is easily reversed
        • risk for immunosuppressed individual
      • High cost for storage
    • Cases
      • Vaccina virus
        • ex.1
          • Insert HIV, rabies genome in nonessential region of harmless poxivirus
        • ex.2
          • Cold adapted (grown at 25ºC) influenza A & B
            • instranasal spray
            • 10-15% NSTI (Necrotizing Soft Tissue Infection)
      • BCG (Bacillus Calmette Guerin vaccine for Mycobacterium tuberculosis)
  • Vector/DNA
  • Antiviral vaccines
  • Antibacteria vaccines
  • tricky definations
    • immunization
      • a procedure designed to increase concentrations of antibodies and/or effector T-cells which are reactive against infection (or cancer)
    • Vaccination
      • procedure of artificial active immunization
    • vaccine
      • agents of artificial active immunization
        • exeption
          • some times block fertilization
            • contraceptive vaccines
          • some times treat allergy
            • T cell vaccine
              • eliminate autoimmune T cells by using "bad T cells'" TCR as antigen ingection
      • benefit-to-risk ratio
        • benifits
          • lasting time of immunity
          • Qualitity
            • humoral and cellular activation
          • Cost
            • production
            • Storage
            • Application
        • risk
          • Autoimmunity/hypersensitivity
          • infection
    • Passive immunization
      • individual acquires immunity through the transfer of antibodies formed by an immune individual or animal.
        • via natural maternal serum/milk or artificial immune serum
        • not permenant, with out activation of clonal expansion, no memory cells
    • Active immunization
      • Immunization through providing antigen but not antibody
        • activates clonal expantion, permanent effect
        • may be artifatial or natural infection
• Drugs
  • features
    • origin
      • natural
      • Synthetic
      • Semisynthetic
        • modified natural origin
          • most resent new antibiotics
    • range of effectiveness
      • Broad spectrum
      • Narrow spectrum
    • production
      • nature
      • synthesis
    • Half life
      • high half life ensure effectivness to target tissue
        • like coat should be stomach acid resistence
  • antiviral
    • Herpesvirals antivirals
      • viral DNA polymerase inhibitors
        • nucleoside analogue
          • acyclovir
          • Gancyclovir
          • cidofovir
        • pyrophosphate analogue
          • Foscarnet
    • Influenza antivirals
      • Amantidine (Rimantadine)
        • block M2 channel
          • M2 mutations develop resistence
          • Side effect: GI or CNS
      • Zanamivir (Relenza) and Oseltamivir (Tamiflu)
        • Neuraminidase Inhibitors
          • sialic acid analogous
          • 18% resistence
          • for both type A&B
          • effect best in early stages
    • HIV antivirals
      • Entry Inhibitors
        • binds to macrophages' receptor CCR5
      • Fusion inhibitors:
        • Only one FDA-approved drug: fuzeon
      • RTIs: reverse transcriptase inhibitors
        • nucleoside-analogue RTIs (NRTIs)
        • non-nucleoside-analogue RTIs (NNRTIs)
          • distorts reverse transcriptase binding to RNA template
      • Integrase Inhibitors
      • PIs: protease inhibitors
    • HBV antivirals
      • Interferon
      • reverse transcriptase inhibitor
        • nucleoside analogue
  • antibiotics
    • drops infectious desease motality from 0.797% to 0.036%
    • Antimicrobial susceptibility patterns
      • Bacteriostatic
        • Only inhibits growth but not kill bacteria
          • like inhibits protein synthesis
      • Bactericidal
        • kill bacteria but not lysis cell
      • Bacteriolytic
        • kill and lysis the cell
    • Antibiotic combinations
      • Reduce emergence of antibiotic resistance
      • results
        • Synergism
          • target different steps of route
        • Antagonism
          • ex bactericidal+bacteriostatic
    • QUNATIFY antibiotics' effects
      • Minimum Inhibitory Concentration (MIC)
        • observed growth reduction
      • Minimum Bactericidal Concentration (MBC)
        • Kills all, no recovery
    • Achieve selective toxicity
      • Target bacterial
        • Cell wall synthesis
          • β-Lactams inhibits transpeptidase which cross-links gram(+) peptidleglycan.
            • penicillin contains a β-lactams ring
          • most astonishing bacterial defense
            • producing enzyme β-lactamase
              • so use the enzymes inhibitor: e.x. potassium clavulanate to combine penicilin
        • Plasma membrane
          • effects selective permeability
        • ribosome
          • 50s
          • 30s
            • Streptomycin Causes Misreading of mRNA
          • transcription initiation
          • transcription elongation
            • Tetracyclin..
              • blocks incomming tRNA binds to A site
            • Erythromycin
              • blocks ribosome translocation
              • Resistance due to enzymatic methylation of 23S rRNA
        • DNA replication
          • gyrase
            • Ciprofloxacin
              • resistance due to mutations in the gyrase A subunit.
              • extremely broad ranged
            • Novobiocin
              • compete with ATP for binding to the B subunit of this enzyme and inhibit the ATP-dependent DNA supercoiling catalysed by gyrase.
              • resistance due to mutations in B subunit
        • RNA transcription
          • RNA pol
            • Rifampin
              • interferes with transcription initiation complex
              • fast resistence for mutations in RNA polymerase
                • so it self should not be used
        • metabolites
          • Tetrahydrofolate (THF) synthesis inhibitor
            • Sulfonamides
              • strucural analogous of paba
            • Trimethoprim
              • inhibits bacterial dihydrofolic acid reductase (DHFR; 105 greater effect on prokaryotic than eukaryotic enzyme)
    • Super bugs: microbes with multiple resistences
      • MRSA
        • Methicillin Resistant Staphylococcus aureus
        • Prevalence
          • Community acquired (CA) MRSA
            • Pandemic: 21-29% in adults and 35-50% in children
            • not multi-drug resistence
          • Healthcare associated (HA) MRSA
            • multi-frug resistence
        • Genetic elements
          • mec gene – staphylococcal chromosomal cassette (SCCmec)
            • 5 types
            • MecA encodes PBP2a
              • alternative PBP(enzyme penicilin targets)
              • Resulting peptidoglycan is structurally different but functional.
              • B-lactamase genes can down regulates MecA gene transcripts
        • new antibiotics
          • •Linezolid •Quinupristin-dalfopristin •Daptomycin •Lysostaphin
      • VISA
        • Vancomycin intermediate susceptible strains
          • a little resistence to vancomycin
        • altered peptidoglycan biosynthesis which causes thicker cell walls and decreased drug exposure to the cytoplasmic membrane
      • VRSA
        • Vancomycin resistence strain
          • MIC>=32 ug/ml
        • Vancomycin binds terminal dipeptide in peptide side-chain and inhibits transglycosylation and transpeptidation
          • Vancomycin is unable to bind to its target site due to an altered terminal peptide.
      • Superbug-TB
        • Pathogen grows in macrophage and may become persistent
        • Thick lipid-rich outer membrane with mycolic acid limits uptake of antibiotics
        • Narrow porin channel transports b-lactams
    • against superbugs
      • Virulence genes target Antisense RNA
      • Develop New antibiotics
      • Use cocktails
      • Ristrict antibiotics use
      • track resistence data