Cellular components

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Cellular components
2013-08-29 23:29:50

Cellular components
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  1. •When
    microorganism crosses the epithelial barrier 
    recognized by
    •mononuclar phagoctyes and tissue macrophages
  2. •mononuclar phagoctyes and tissue macrophages are mostly in
  3. what is the second major population of
  4. •Binding
    of the cell surface receptors leads to two important sequences
    1.Phagocytosis and killing of the engulfed pathogen

    • 2.Release of proteins called cytokines and chemokines (chemoattractant cytokines) and
    • other chemical mediators which initiate inflammation and attract more neutrophils
  5. important role of Cytokines
    • •induce
    • expression of costimulatory
    • molecules on macrophages and dendritic cells (APC) which will initiate the adaptive immune system
  6. •Phagocyte
    binding to microbes is greatly enhanced in the presence of
  7. opsonins are
    • Host
    • derived proteins that coats the microbe and enhances its phagocytosis
  8. example od opsonoins
    • •complement proteins (C3b),
    • antibodies
  9. Name some phagocyte receptor
    • CR1, CR3, CR4
    • FcεR, FcγR I,II,III, FcμR
    • TLRs
    • scavenger receptor 
    • receptor for defensins
  10. macrophages and neutrophils 
    pathways to kill microorganisms
    • 1.Oxidative
    • and non-oxidative attack

    • 2.Oxidative
    • mechanism

    –Uses two intermediates

    • 1.Reactive oxygen species/
    • intermediate (ROS/ROI)

    • 2.Reactive nitrogen
    • species/intermediate (RNS/RNI)
  11. The ROS are generated by the
    • •NADPH phagosome oxidase (phox)
    • enzyme complex.
  12. •Formation of a phagosome
    results in
    • 1.Activation of protein kinase which
    • 2.Phosphorylates NADPH dependent oxidases located in the phagosomal membrane; the NADPH dependent oxidases catalyzes
    • 3.The conversion of molecular oxygen to the highly reactive superoxide anion (O2 to O2-) which is highly toxic to engulfed microbes

  13. •Superoxide
    anion further reduced by superoxide dismutase  to ROI (all potent oxidizing agents) like
    •Hydrogen peroxide

    •Singlet oxygen

    •Hydroxyl radicals

    •Hypochlorous acid

  14. Myeloperoxidase is
    • •released
    • from intracellular granules reacts with Cl and H ions in the presence of hydrogen
    • peroxide to produce hypochlorite, chlorine
  15. Generation of reactive nitrogen species (RNS)
    • •Nitric
    • oxide generated by the action of nitric oxide synthetase combines with superoxide to give RNS.
  16. •Phagocyte
    protected by the these toxic radicals by the production of 3 enzymes
    •Superoxide dismutase


    •Glutathione peroxidase
  17. •Non

    Additional defense mechanisms like



  18. Chronic granulomatous disease
    • •Defect
    • in the ability of phox to generate ROI

    • •Defect
    • in production of subunits of NADPH oxidase
  19. what happens when •Defect
    in production of subunits of NADPH oxidase
    • •Oxygen
    • dependent intermediates are not generated

    • •Myeloperoxidase
    • system remains unaffected
  20. •what happens in case of infections with catalase producing bacteria?
    the bacteria will produce H2O2 as metabolism byproduct and enzyme Myeloperoxidase can produce hypochlorite and kill the bacteria
  21. Effector
    Functions of Macrophages
    • 1) TLR 
    • 2) IFN-γ receptor
  22. Molecules produced in activated macrophages and their effects
    • 1)phagocyte oxidase --> reactive oxygen species (ROS) --> killing of microbes 
    • 2) iNOS --> nitric oxide --> killing of microbes 
    • 3) cytokines TNF, IL-1, IL-12 --> inflammation, enhanced adaptive immunity 
    • 4) fibroblaast growth factors, metalloproteinases --> tissue remodeling
  23. NK cells are identified by what receptors?
    •CD56+, CD16+ and CD3-(no CD3)
  24. NK cell's •Possess
    Killer activation receptors (KAR)
    • •Recognize stress associated molecules like MICA
    • and MICB that appear on the surface of infected, transformed cells
  25. KIR bind to ----- and won't kill cell
    • MHCI molecules which are present on all
    • nucleated cells
  26. ????antibody  (IgG)mediated cell mediateed
  27. how NK cell will kill
    •Certain viruses and malignant cells do not express MHC I or low level expression
  28. Effector functions of NK cells
    •To kill infected cells

    •To activate macrophages to destroy phagocytosed microbes
  29. how NK will help killing of phagocytosed microbes?
    NK binds to --> macrophage with phagocytosed microbes --> secrets IL-12 --> goes to NK --> NK secrets IFN-γ --> goes back to macrophage and activates macrophage --> kills the microbes