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Failures of body’s defenses Immunopathology

Failures of body’s defenses Immunopathology. Evasion and subversion of the immune system by pathogens. The immune system is still the big black box. Environment. Immune system. Tolerance. self. Little light at the end of the tunnel. Non-self Dangerous Pathogenic. Immune response.

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Failures of body’s defenses Immunopathology

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  1. Failures of body’s defensesImmunopathology Evasion and subversion of the immune system by pathogens

  2. The immune system is still the big black box Environment Immune system Tolerance self Little light at the end of the tunnel Non-self Dangerous Pathogenic Immune response

  3. Virus 3 hrs Diversity Fast development 3 hrs PATHOGENS HAVE SHORT GENERATION TIME PATOGENS Bacteria Viruses parasites

  4. Humans have longer generation time, Need a sophysticated protection system Birth Development education Reproducrion at 35

  5. Genetic variation prvents long-term immunity Highly variable capsular polysaccharide molecules---- serotypes

  6. High rate of mutation and recombination help influenza virus to escape immune recognition (Antigenic drift)

  7. ORIGINAL ANTIGENIC SIN

  8. High rate of recombination help influenza virus to escape immune recognition Large changes can occur rapidly by recombination between virus particles made in different hosts

  9. Viruses may interfere with the presentation of viral antigens (HSV, EBV, CMV, etc) Strategyies of Human cytomegalovirus (HCMV)

  10. Gene rearrangement is used by Trypanosomes to change cell surface antigens Cell surface glycoproteins are encoded by separate genes Approx. 1000 vatiable surface glycoproteins (VSG) Antibody controls parasite, but always a new variant emerges Deposition of immune complexes Inflammation CNS involvement, neuronal damage, sleeping sickness--- coma The pilin protein of Nesseria gonorrhoeae is also variable and only one is expressed at any time.

  11. ‘Seek and hide’ by Listeria monocytogenes, an intracellular bacterium

  12. Bacterial superantigens bridge α:β T-cell receptors and MHC class II molecules in the absence of a specific peptide.

  13. Macrophages are responsible for Phagocytosis of bacteria and other foreign cells and for activation of other immune cells Macrophage Bacteria

  14. Normally ingested bacteria and other things get sent to the lysosome for destruction by low pH and proteolysis Uh oh! bacterium

  15. But the TB bacterium has a better idea-- It remodels the endosome to be its new home!

  16. Avoiding the lysosome also reduces presentation of bacterial peptides to the immune system by the MHC proteins

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