1. Infectious Diseases of the Cardiovascular and Lymphatic Systems

2. The Cardiovascular System

Heart

Blood vessels

Lymphatics

Lymph nodes, spleen, MALT

RBC

WBC

• Monocyte Macrophage

• T, B, NK lymphocytes

3. The Blood

Carries O 2 , CO 2 , nutrients

Cells + plasma

Infectious agents in the blood

Bacteremia / viremia bacteria / viruses in blood

Septicemia growth of

• bacteria in blood

Septic shock

endotoxin (LPS) release

macrophage cytokines

low blood pressure (leaky capillaries),

high fever

4. Cardiovascular System Defenses

Defensins - antimicrobial proteins in lysosomes of phagocytic cells

Neutrophils, antibodies, complement

Filtering function of Lymph Nodes

No normal flora

Transient flora ?

Infectious agents in blood aresystemic

5. Selected Bacterial Infectionsof the Blood

Plague Yersinia pestis

Lyme Disease Borrelia burgdorferi

Rocky Mountain Spotted Fever

-Rickettsia rickettsii

6. Yersinia pestis

Cause of Plague

Gram negative rod

Grows in digestive tract of flea =vector

Reservoiris rodents, prairie dogs

Endemicabove 4,000 ft elevation in Arizona

7. The infection cycle ofYersinia pestis. 8. Animal Reservoirs United States 9. Plague in Arizona 10. Prairie Dog Plague, Flagstaff 2001

99 colonies observed

49 colonies experienced >99% mortality May-September 2001

Y. pestisconfirmed as cause of die offs at 19 colonies

11. Bubonic Plague

Transmitted by flea bite

Y. pestisenters blood and grows in macrophages in lymph nodes

Swollen lymph nodes arebuboes

12. Plague

Septicemicplague

• proliferation in blood

• endotoxin shock

Pneumonic plague

• lung infection

• 100% mortality

• spread by droplets

Curable with antibiotic

if diagnosed quickly

13. Lyme Disease

Primary Lesion

• bulls-eye rash on skin

Secondary lesion

• flu-like symptoms, neurological symptoms

Tertiary lesion

• inflammation of large joints

14. Lyme Arthritis

Immune systemType III hypersensitivityto

persisting antigen

antigen-antibody

complexes

inflammation, tissue

damage by neutrophils

Treated with antibiotics

15. Lyme Disease is caused by Borrelia burgdorferi*

Spirochetes are very narrow spiral-shaped bacteria

Gram negative

Motile

*After Willy Burgdorfer 16. Lyme Disease Vectors

Tickvectorbites infectedreservoir(deer, mouse) and becomes infected; transmits disease to humans through bites

17. Disease emerged when humans moved into tick/reservoir environment Cycle of infectionwith B. burgdorferi 18. Rocky Mountain Spotted Fever

Fever, chills, headache, muscle pain

Redblack rash

Transmitted to

humans by tick bites

Now found mostly in

Eastern Atlantic states

19. Rickettsia rickettsii

Gram negative bacillus or coccobacillus

Obligate intracellularparasite

20. Rickettsiaand Obligate Intracellular Parasitism

Bind to cell surface and are taken intoendothelial cells by phagocytosis

Escape from phagosome into cytoplasm

Have ETC

Obtain nutrients, NAD +and CoA from host

Cause capillaries to degrade

21. Vectors : Wood Tick and Dog Tick 22. RMSF Epidemiology 1942-2002 23. Rocky Mountain Spotted Fever

Treatable with antibiotics

Diagnosed using fluorescent antibodies on tissue samples, PCR

20% of untreated cases and 5-10% of treated cases are fatal

24. Some Virus Infections of the Cardiovascular System

Persistent Herpesviruses

• Human herpes viruses 4,5,6,7,8!

Viral hemorrhagic Fevers

• Yellow Fever, Dengue Fever, Ebola, Lassa Fever

HIV

25. Virus Infections of the Cardiovascular System Persistent Herpesviruses in lymphocytes Human Herpes 4:Mononucleosis (=Epstein Barr virus) MonoInfectious Mono Human Herpes 5: Cytomegalovirus(= Cytomegalovirus) Inclusion Disease Human Herpes 6 Roseola Human Herpes 7? Human Herpes 8 Kaposis Sarcoma (in AIDSpatients) 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. Viral Hemorrhagic fevers

Viral infection Reservoir Location

Yellow fever Aedes agypti Cent Africa S. America

Dengue fever Aedes agypti World-wide Tropical

Ebola Fruit BatCent Africa

Lassa fever Rodent West Africa

28. Viral Hemorrhagic fevers

Capillary fragility and leakage

Disruption of the blood clotting system

• Bleeding, Hemorrhage

Liver damage, Hepatitis

High Fatality rate

29. Human immunodeficiency virus (HIV)

Blood-Borne Viral infection

Infects helper T lymphocytes (CD4 receptor)

Acquired immunodeficiency syndrome

Long (Latent)

incubation period

30. HIV has specific glycoprotein receptors that bind to CD4 receptors of T cells. CD4 CRCX5 31. Four main stages of an HIV infection 32. Stages of an HIV infection Antibody resistant variants andNeutralizingantibody 33. Sources and routes of infection by HIV

STD:

MSM

Prostitution

Heterosexual

Blood injection IV drug use 34. Some important secondary infections in AIDS 35. AIDS and Herpesviruses ..an example: Kaposis Sarcoma .caused by Human Herpes 8 HHV-8 causesa mixed cell tumor ofLymphocytes, fibroblasts, and blood vesselsOn the skin, esophagus and many other sites 36. Nucleoside analogs and protease inhibitors are effective therapies used to treat HIV infections. 37. HIVTransmission U.S. comparedTo the World 38. HIV/AIDS prevalence in the world 39. HIV/AIDS prevalence in the world