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  1. 1. Infectious Diseases of the Cardiovascular and Lymphatic Systems
  2. 2. The Cardiovascular System <ul><li>Heart </li></ul><ul><li>Blood vessels </li></ul><ul><li>Lymphatics </li></ul><ul><li>Lymph nodes, spleen, “MALT” </li></ul><ul><li>RBC </li></ul><ul><li>WBC </li></ul><ul><ul><li>Monocyte  Macrophage </li></ul></ul><ul><ul><li>T, B, NK lymphocytes </li></ul></ul>
  3. 3. The Blood <ul><li>Carries O 2 , CO 2 , nutrients </li></ul><ul><li>Cells + plasma </li></ul><ul><li>Infectious agents in the blood </li></ul><ul><li>Bacteremia / viremia – bacteria / viruses in blood </li></ul><ul><li>Septicemia – growth of </li></ul><ul><ul><li>bacteria in blood </li></ul></ul><ul><li>Septic shock </li></ul><ul><li> endotoxin (LPS) release </li></ul><ul><li> macrophage cytokines </li></ul><ul><li> low blood pressure (leaky capillaries), </li></ul><ul><li> high fever </li></ul>
  4. 4. Cardiovascular System Defenses <ul><li>Defensins - antimicrobial proteins in lysosomes of phagocytic cells </li></ul><ul><li>Neutrophils, antibodies, complement </li></ul><ul><li>Filtering function of Lymph Nodes </li></ul><ul><li>No normal flora </li></ul><ul><li>Transient flora ? </li></ul><ul><li>Infectious agents in blood are systemic </li></ul>
  5. 5. Selected Bacterial Infections of the Blood <ul><li>Plague – Yersinia pestis </li></ul><ul><li>Lyme Disease – Borrelia burgdorferi </li></ul><ul><li>Rocky Mountain Spotted Fever </li></ul><ul><li>- Rickettsia rickettsii </li></ul>
  6. 6. Yersinia pestis <ul><li>Cause of Plague </li></ul><ul><li>Gram negative rod </li></ul><ul><li>Grows in digestive tract of flea = vector </li></ul><ul><li>Reservoir is rodents, prairie dogs </li></ul><ul><li>Endemic above 4,000 ft elevation in Arizona </li></ul>
  7. 7. The infection cycle of Yersinia pestis.
  8. 8. Animal Reservoirs – United States
  9. 9. Plague in Arizona
  10. 10. Prairie Dog Plague, Flagstaff 2001 <ul><li>99 colonies observed </li></ul><ul><li>49 colonies experienced >99% mortality May-September 2001 </li></ul><ul><li>Y. pestis confirmed as cause of die offs at 19 colonies </li></ul>
  11. 11. Bubonic Plague <ul><li>Transmitted by flea bite </li></ul><ul><li>Y. pestis enters blood and grows in macrophages in lymph nodes </li></ul><ul><li>Swollen lymph nodes are buboes </li></ul>
  12. 12. Plague <ul><li>Septicemic plague </li></ul><ul><ul><li>proliferation in blood </li></ul></ul><ul><ul><li>endotoxin shock </li></ul></ul><ul><li>Pneumonic plague </li></ul><ul><ul><li>lung infection </li></ul></ul><ul><ul><li>100% mortality </li></ul></ul><ul><ul><li>spread by droplets </li></ul></ul><ul><li>Curable with antibiotic </li></ul><ul><li> if diagnosed quickly </li></ul>
  13. 13. Lyme Disease <ul><li>Primary Lesion </li></ul><ul><ul><li>bulls-eye rash on skin </li></ul></ul><ul><li>Secondary lesion </li></ul><ul><ul><li>flu-like symptoms, neurological symptoms </li></ul></ul><ul><li>Tertiary lesion </li></ul><ul><ul><li>inflammation of large joints </li></ul></ul>
  14. 14. Lyme Arthritis <ul><li>Immune system Type III hypersensitivity to </li></ul><ul><li> persisting antigen </li></ul><ul><li> antigen-antibody </li></ul><ul><li>complexes </li></ul><ul><li> inflammation, tissue </li></ul><ul><li>damage by neutrophils </li></ul><ul><li>Treated with antibiotics </li></ul>
  15. 15. Lyme Disease is caused by Borrelia burgdorferi* <ul><li>Spirochetes are very narrow spiral-shaped bacteria </li></ul><ul><li>Gram negative </li></ul><ul><li>Motile </li></ul>*After Willy Burgdorfer
  16. 16. Lyme Disease Vectors <ul><li>Tick vector bites infected reservoir (deer, mouse) and becomes infected; transmits disease to humans through bites </li></ul>
  17. 17. Disease emerged when humans moved into tick/reservoir environment Cycle of infection with B. burgdorferi
  18. 18. Rocky Mountain Spotted Fever <ul><li>Fever, chills, headache, muscle pain </li></ul><ul><li>Red  black rash </li></ul><ul><li>Transmitted to </li></ul><ul><li>humans by tick bites </li></ul><ul><li>Now found mostly in </li></ul><ul><li>Eastern Atlantic states </li></ul>
  19. 19. Rickettsia rickettsii <ul><li>Gram negative bacillus or coccobacillus </li></ul><ul><li>Obligate intracellular parasite </li></ul>
  20. 20. Rickettsia and Obligate Intracellular Parasitism <ul><li>Bind to cell surface and are taken into endothelial cells by phagocytosis </li></ul><ul><li>Escape from phagosome into cytoplasm </li></ul><ul><li>Have ETC </li></ul><ul><li>Obtain nutrients, NAD + and CoA from host </li></ul><ul><li>Cause capillaries to degrade </li></ul>
  21. 21. Vectors : Wood Tick and Dog Tick
  22. 22. RMSF Epidemiology 1942-2002
  23. 23. Rocky Mountain Spotted Fever <ul><li>Treatable with antibiotics </li></ul><ul><li>Diagnosed using fluorescent antibodies on tissue samples, PCR </li></ul><ul><li>20% of untreated cases and 5-10% of treated cases are fatal </li></ul>
  24. 24. Some Virus Infections of the Cardiovascular System <ul><li>Persistent Herpesviruses </li></ul><ul><ul><li>Human herpes viruses 4,5,6,7,8 ! </li></ul></ul><ul><li>Viral hemorrhagic Fevers </li></ul><ul><ul><li>Yellow Fever, Dengue Fever, Ebola, Lassa Fever </li></ul></ul><ul><li>HIV </li></ul>
  25. 25. Virus Infections of the Cardiovascular System Persistent Herpesviruses in lymphocytes Human Herpes 4: Mononucleosis (=Epstein Barr virus) “Mono” “Infectious Mono” Human Herpes 5: Cytomegalovirus (= Cytomegalovirus) Inclusion Disease Human Herpes 6 Roseola Human Herpes 7 ? Human Herpes 8 Kaposi’s Sarcoma (in AIDS patients)
  26. 26. Infectious mononucleosis Infects B lymphocytes - viral latency in B lymphocytes A c ause of Chronic fatigue syndrome? Cytomegalovirus Inclusion Disease Newborns, rarely. A cause of mental retardation? Viral latency is in lymphocytes, and kidney cells. Severe infection in immunocompromised patient HIV Cancer and transplant patients
  27. 27. Viral Hemorrhagic fevers <ul><li>Viral infection Reservoir Location </li></ul><ul><li>Yellow fever Aedes agypti Cent Africa S. America </li></ul><ul><li>Dengue fever Aedes agypti World-wide Tropical </li></ul><ul><li>Ebola Fruit Bat Cent Africa </li></ul><ul><li>Lassa fever Rodent West Africa </li></ul>
  28. 28. Viral Hemorrhagic fevers <ul><li>Capillary fragility and leakage </li></ul><ul><li>Disruption of the blood clotting system </li></ul><ul><ul><li>Bleeding, Hemorrhage </li></ul></ul><ul><li>Liver damage, Hepatitis </li></ul><ul><li>High Fatality rate </li></ul>
  29. 29. Human immunodeficiency virus (HIV) <ul><li>Blood-Borne Viral infection </li></ul><ul><li>Infects helper T lymphocytes (CD4 receptor) </li></ul><ul><li>Acquired immunodeficiency syndrome </li></ul><ul><li>Long (Latent) </li></ul><ul><li>incubation period </li></ul>
  30. 30. HIV has specific glycoprotein receptors that bind to CD4 receptors of T cells. CD4 CRCX5
  31. 31. Four main stages of an HIV infection
  32. 32. Stages of an HIV infection Antibody resistant variants and Neutralizing antibody
  33. 33. Sources and routes of infection by HIV <ul><li>STD: </li></ul><ul><li>MSM </li></ul><ul><li>Prostitution </li></ul><ul><li>Heterosexual </li></ul>Blood injection IV drug use
  34. 34. Some important secondary infections in AIDS
  35. 35. AIDS and Herpesviruses …..an example: Kaposi’s Sarcoma ….caused by Human Herpes 8 HHV-8 causes a mixed cell tumor of Lymphocytes, fibroblasts, and blood vessels On the skin, esophagus and many other sites
  36. 36. Nucleoside analogs and protease inhibitors are effective therapies used to treat HIV infections.
  37. 37. HIV Transmission U.S. compared To the World
  38. 38. HIV/AIDS prevalence in the world
  39. 39. HIV/AIDS prevalence in the world

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