Term
| What are 2 ways that pathogens can gain access to intracellular environments? |
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Definition
1) Invasins (non-phagocytic cells)
2) Phagocytosis |
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Term
| How can pathogens evade phagosome/lysosome fusion? |
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Definition
1) Prevent fusion
2) Modify vacuole
3) Escape vacuole
4) Tolerate environment
5) Reduce acidification |
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Term
| What are 4 consequences for pathogens of macrophage activation through either TLR or IFN-y? |
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Definition
1) ROI
2) RNI
3) Increased P-L fusion
4) Increased MHC-II |
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Term
| How do M. tuberculosis and HCMV avoid detection by CD4 T cells? |
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Definition
1) M. tuberculosis down-regulates MHC-II expression during chronic infection
2) HCMV has protein that degrades MHC-II alpha chains and another that prevent invariant chain interactions |
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Term
| How do Adenovirus, HSV and HCMV avoid detection by CD4 T cells? |
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Definition
1) Adenovirus makes a protein that prevents MHC-I transport
2) HSV makes protein that interferes with TAP
3) CMV inhibits TAP and leads to MHC-I degredation |
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Term
| How does Listeria monocytogenes escape immune reactions? |
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Definition
Causes meningitis in newborns and bacteremia/meningitis in Immunocompromised
1) Taken up in the phagosome, and produces Listeriolysin O (hlyA gene) which breaks open phagosome and allows entry to the cytoplasm.
2) Replicates in cytoplasm and forms actin "tail" by nucleating host actin (actA), which gives it motility within and between cells
** Similar actions are seen in Trypanasoma cruzi, Shigella and Rickettsia ** |
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Term
| What biological characteristics define Listeria monocytogenes? |
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Definition
-Small facultative anaerobe
- Gram-positive rod with incomplete beta-hemolysis
- catalase +
- oxidase-negative
- Grows optimally at 30-37 degrees but will persist at 4 |
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Term
| What is the reservoir/transmission route of Lysteria monocytogenes? |
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Definition
1) Food borne (processed and soft cheeses)
2) Found in soil
-zoonotic with cattle
-placental passage. |
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Term
| What virulence factors are associated with Lysteria monocytogenes? |
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Definition
1) Listeriolysin (hlyA) breaks open phagosome
2) Actin "tail" from host actin (actA) gives motion and intercellular transport |
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Term
| How do you diagnose/treat a case of Listeria infection? |
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Definition
1) CSF and blood yielding Listeria (CSF may also have macrophages)
**Gram stain is UNRELIABLE
2) If gram stain/CSF is not positive, but still suspected, use TM/SFX or Ampicillin
BE CAREFUL WITH FOODS for pregnant mothers |
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Term
A 60 year old patient with COPD and a history of smoking presents with coughing, fever and diarrhea.
Gram stain is negative but a BAL reveals aerobic, gram negative organisms.
What is the pathogenesis of this organism? |
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Definition
Sounds like Legionella pneumophila
1) Replication genes (abundant nutrients)
2) Transmission genes (few nutrients)
3) Remodels phagosome with ER vesicles to look like ER, preventing phag/lys fusion
4) Type IV secretion (dot/icm) to prevent fusion |
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Term
| What biological characteristics define Legionella pneumophila? |
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Definition
- Small aerobic, gram-negative
- Intracellular rod or coccobacillus
- Facultative anaerobe
- Single polar flagellum with multiple fimbriae (pili)
- Nutritionally fastidious |
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Term
| What is the reservoir/transmission of Legionella pneumophila? |
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Definition
1) Biofilm in Water (chlorine-tolerant) from cooling towers, living within amebas and ciliated protozoa
- Can be aerosolized from water, air conditioners, humidifiers, ect.
2) NOT HUMAN TO HUMAN |
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Term
| How do you diagnose a case of Legionella pneumophila? |
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Definition
1) BAL culture
2) Chest radiograph for infiltrates
3) Gram stain NOT RELIABLE
4) Urinary antigen test for LPS (only for sero-group 1 in US) |
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Term
| How do you treat/prevent cases of Legionella pneumophila? |
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Definition
1) Choose based on phagocyte penetration (new macrolides and FQs) with reaction taking 3-5d
2) Survey hospital environment and disinfect cooling towers |
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Term
A patient presents with cyclic fevers every 48 hours with paroxysm (cold, hot, sweat).
They note that they recently traveled to Nigeria not undergoing prophylaxis with Mefloquine or Atovaquone/proguanil,
What are the virulence factors of the pathogen? |
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Definition
P. falciparum (PfEMP and Circumsporozoite)
1) PfEMP protein is variable and can cause binding of RBC to many different host proteins
- Expression causes "knobs" on P. falciparum parasitized RBC allowing binding and sequestration of RBC leading to tissue obstruction.
2) Circumsporozoite protein allows sporozoites to bind to and invade hepatocytes (site of replication) |
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Term
| What biological characteristics define Plasmodium? |
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Definition
1) P. falciparum (tropical regions- infect RBCs of all ages with no dormant liver stage)
2) P. vivax and P. ovale (more temperate zones- hypnozoites (latent liver form), so can cause late relapse, but only infects RETICULOCYTES, not all RBCs)
3) P. malariae (very few serious cases) |
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Term
| What is the basic life cycle of Plasmodium? |
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Definition
Sporozoites (mosquito to human), Shizonts (liver multiplication), Merozoites (exit and invade RBCs), Gametocytes (human to mosquito)
1) Sporozoites from mosquito infect humans and travel to liver, and invade hepatocytes
2) Differentiate into schizonts and multiply
3) Differentiate into merozoites and exit (P. vivax and P. ovale also have hypnozoite stage where they remain dormant before becoming merozoites)
4) Invade RBCs, mature, and lyse them, releasing merozoites to infect more.
** Some merozoites become Gametocytes (male and female), which can be taken up by mosquito |
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Term
| What is the reservoir/transmission of Malaria? |
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Definition
1) Anopheles female mosquito-human-mosquito
-Sickle cell confers resistance, because of abnormal RBC shape
- Most severe in naive individuals, children and pregnant women. |
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Term
| How do you diagnose/treat Malaria? |
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Definition
Diagnose
- Blood smear for parasites
- Ring form ONLY seen in falciparum cases
Treat
- Chloroquine (erythrocytic)
- Quinine (erythrocytic)
- Primaquine (exo-erythrocytic in liver stage)
- Artemisin (combination)
- Mefloquine (chloroquine resistant and prophylaxis),
- Atovaquone/proguanil (chloroquine resistant and prophylaxis- $$$)
- Vaccine in development |
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