Infectious Diseases of the Cardiovascular and Lymphatic Systems

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Infectious Diseases of the Cardiovascular and
Lymphatic Systems
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The Cardiovascular System

• Heart
• Blood vessels
• Lymphatics
• Lymph nodes, spleen, MALT
• RBC
• WBC
• Monocyte?Macrophage
• T, B, NK lymphocytes

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The Blood

• Carries O2, CO2, 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

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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 are systemic

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Selected Bacterial Infections of the Blood

• Plague Yersinia pestis
• Lyme Disease Borrelia burgdorferi
• Rocky Mountain Spotted Fever
• - Rickettsia rickettsii

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Yersinia pestis

• Cause of Plague
• Gram negative rod
• Grows in digestive tract of flea vector
• Reservoir is rodents, prairie dogs
• Endemic above 4,000 ft elevation in Arizona

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The infection cycle of Yersinia pestis.
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Animal Reservoirs United States
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Plague in Arizona
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Prairie Dog Plague, Flagstaff 2001

• 99 colonies observed
• 49 colonies experienced 99 mortality
  May-September 2001
• Y. pestis confirmed as cause of die offs at 19
  colonies

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Bubonic Plague

• Transmitted by flea bite
• Y. pestis enters blood and grows in macrophages
  in lymph nodes
• Swollen lymph nodes are buboes

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Plague

• Septicemic plague
• proliferation in blood
• endotoxin shock
• Pneumonic plague
• lung infection
• 100 mortality
• spread by droplets
• Curable with antibiotic
• if diagnosed quickly

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Lyme Disease

• Primary Lesion
• bulls-eye rash on skin
• Secondary lesion
• flu-like symptoms, neurological symptoms
• Tertiary lesion
• inflammation of large joints

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Lyme Arthritis

• Immune system Type III hypersensitivity to
• ? persisting antigen
• ? antigen-antibody
• complexes
• ? inflammation, tissue
• damage by neutrophils
• Treated with antibiotics

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Lyme Disease is caused by Borrelia burgdorferi

• Spirochetes are very narrow spiral-shaped
  bacteria
• Gram negative
• Motile

After Willy Burgdorfer
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Lyme Disease Vectors

• Tick vector bites infected reservoir (deer,
  mouse) and becomes infected transmits disease to
  humans through bites

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Cycle of infection with B. burgdorferi
Disease emerged when humans moved into
tick/reservoir environment
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Rocky Mountain Spotted Fever

• Fever, chills, headache, muscle pain
• Red ? black rash
• Transmitted to
• humans by tick bites
• Now found mostly in
• Eastern Atlantic states

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Rickettsia rickettsii

• Gram negative bacillus or coccobacillus
• Obligate intracellular parasite

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Rickettsia and Obligate Intracellular Parasitism

• Bind to cell surface and are taken into
  endothelial cells by phagocytosis
• Escape from phagosome into cytoplasm
• Have ETC
• Obtain nutrients, NAD and CoA from host
• Cause capillaries to degrade

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Vectors Wood Tick and Dog Tick
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RMSF Epidemiology 1942-2002
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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

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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

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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 Kaposis Sarcoma (in AIDS
  patients)

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Infectious mononucleosisInfects B lymphocytes -
viral latency in B lymphocytesA cause of Chronic
fatigue syndrome?Cytomegalovirus Inclusion
DiseaseNewborns, rarely. A cause of mental
retardation?Viral latency is in lymphocytes, and
kidney cells.Severe infection in
immunocompromised patient HIV Cancer and
transplant patients
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Viral Hemorrhagic fevers

• Viral infection Reservoir Location
• Yellow fever Aedes agypti Cent Africa
  S. America
• Dengue fever Aedes agypti World-wide T
  ropical
• Ebola Fruit Bat Cent Africa
• Lassa fever Rodent West Africa

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Viral Hemorrhagic fevers

• Capillary fragility and leakage
• Disruption of the blood clotting system
• Bleeding, Hemorrhage
• Liver damage, Hepatitis
• High Fatality rate

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Human immunodeficiency virus (HIV)

• Blood-Borne Viral infection
• Infects helper T lymphocytes (CD4 receptor)
• Acquired immunodeficiency syndrome
• Long (Latent)
• incubation period

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HIV has specific glycoprotein receptors that bind
to CD4 receptors of T cells.
CD4 CRCX5
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Four main stages of an HIV infection
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Stages of an HIV infection
Antibody resistant variants and Neutralizing
antibody
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Sources and routes of infection by HIV
Blood injection IV drug use

• STD
• MSM
• Prostitution
• Heterosexual

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Some important secondary infections in AIDS
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AIDS and Herpesviruses..an example Kaposis
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
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Nucleoside analogs and protease inhibitors are
effective therapies used to treat HIV infections.
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HIV Transmission U.S. compared To the World
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HIV/AIDS prevalence in the world
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HIV/AIDS prevalence in the world