CME: Sepsis Pathogenesis – Microbial factors

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CME: Sepsis Pathogenesis – Microbial factors

  1. 1. By Dr J. Stalin Roy Prof K.S. Chenthil’s Unit (IMCU) STANLEY MEDICAL COLLEGE
  2. 2. INNATE IMMUNE RESPONSE TO INVADING BACTERIA <ul><li>The innate immune system is able to detect pathogens via Pattern Recognizing Receptors (PRR) </li></ul><ul><li>PRR are able to recognize conserved motifs expressed by pathogens known as Pathogen Associated Molecular Pattern (PAMP) </li></ul><ul><li>Examples of PAMP are LPS, Lipotechoic acid, peptidoglycans, lipopeptides, flagellin, bacterial DNA </li></ul>
  3. 4. PRR and PAMP LTA LPS
  4. 5. Various PAMP, PRR and pathogens
  5. 7. Bactericidal/permeability increasing protein-BPI <ul><li>BPI is another important endotoxin binding protein produced by neutrophils . </li></ul><ul><li>Similar in structure to LBP but has distinctly antagonistic function i.e. it inhibits the LPS delivery to CD14 ( endogenous antiendotoxin ). </li></ul><ul><li>Hence the relative concentration of these two determine the net effect of LPS release. </li></ul><ul><li>In human plasma the concentration of LBP is 2-3 times that of BPL whereas in abscess cavities BPL is much higher . </li></ul>
  6. 9. Bacterial superantigens <ul><li>These are protein based exotoxins produced by staphylococci, streptococci and other pathogens that share unusual immunologic property. </li></ul><ul><li>They have the capacity to activate a large number of CD4+ T cells bypassing the usual process of antigen processing and presentation </li></ul>
  7. 10. Normal antigen Antigen presenting cell (APC) Phagocytose invading bacteria The CD4+ T cell gets activated and proliferates clonally Broken down bacterial antigens are processed and expressed on the surface of MHC II Each processed antigen is recognized by specific T cell receptor (TCR)
  8. 11. Super antigen Super antigen binds directly to MHC II (non antigen binding domain) It is then able to bind to non matching TCR Leads on to activation of more than 10% of the circulating lymphocytes Massive release of inflammatory mediators
  9. 12. TSST -1 superantigen
  10. 13. TLR/NOD –> NFKB –> T cell activation
  11. 14. Gram positive and fungal causative organisms
  12. 15. Summary

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