Micro Block III Raw – Flashcards
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| What are the different routes of infection to the CNS |
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| Blood stream, nerves, direct spread from adjacent focus of infection |
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| What is the most common cause of bacterial infection of the nervous system in newborns? |
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| Group B Strep (S. agalactiae) Also E. coli, Listeria, Klebsiella, and others |
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| Which E. coli serotype causes neonatal meningitis? |
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| K-1 E. coli |
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| How do newborns most commonly contract bacterial infections of the meningitis? |
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| At birth due to colonization of th ebirth canal |
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| What is the most common cause of bacterial infection of the nervous system in infants and children? |
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| Strep pneumoniae Neisseria meningitidis Haemophilus influenza |
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| What is the most common cause of acute purulent mingitis? |
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| Strep pneumoniae Neisseria meningitidis Haemophilus influenza |
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| Meningitis associated with trauma, neurosurgery, or foreign intracranial bodies is most often caused by what pathogens? |
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| Staph aureus Staph epidermidis Strep pneumoniae Pseudomonas |
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| Intracranial abscesses not associated with trauma or surgery is usually due to what? |
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| Microaerophilic or anaerobic streptococci, anaerobic Gram-negative bacteria (often mixed aerobic and anaerobic flora of upper respiratory tract origin) |
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| What is the rule of thumb when determining whether a pathogen is intracellular or extracellular? |
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| Intracellular causes granulous lesions Extracellular causes pyogenic and pus formation |
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| What is purulent meningitis? |
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| An infection of the meninges associated with marked acute inflammatory exudates, usually due to bacterial infection |
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| What are the symptoms of purulent meningitis? |
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| Acute onset and rapid progression of fever, stiff neck, irritability, neurologic dysfunction, and PMNs |
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| What are the characteristics of chronic meningitis? What causes it? |
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| Insidious onset, progresses over weeks Most often caused by mycobacteria but can also be due to fungi (granulomatous inflammations) and protozoa (rare) |
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| What is asceptic meningitis? |
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| A syndrome of meningeal inflammation associated with an increase of cells, primarily lymphocytes and mononuclear cells of the CSF Usually due to viral infection |
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| What usually precedes asceptic meningitis? |
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| Viral infections CSF shows an absence of readily cultivable bacteria or fungi |
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| What is encephalitis? |
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| CNS dysfunction due to infection: seizures, paralysis, disordered mentation CSF findings may or may not be comparable with asceptic meningitis |
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| What causes encephalitis? |
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| Most often viral infection but can also be due to acute or chronic demyelinating diseases such as postinfectious or allergic encephalomyelitis syndrome |
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| What is Poliomyelitis? |
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| Selective destruction of anterior motor horn cells in the spinal cord and/or brainstem |
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| What causes poliomyelitis? |
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| Most commonly due to polio virus Can also be due to Coxsackie virus type A7 or other enteroviruses |
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| What is acute polyneuritis? |
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| An inflammatory disease of the peripheral nerves with characteristic symmetric flaccid paralysis of muscles |
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| What causes acute polyneuritis and how is it prevented? |
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| Rabies, influenza, polio, Hep A These diseases are uniquely prevented using killed viruses (RIP Always) Also can be associated with C. diptheriae, enteric bacterial pathogens, CMV, EBV, and others |
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| What is Reye's syndrome? |
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| Encephalopathy with fatty infiltration of viscera Seen in childhood, associated with the flu, chicken pox, and the measles |
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| What causes Reye's syndrome? |
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| Cerebral edema, hepatic dysfunction, or hyperammonemia is followed by treatment with aspirin which can precipitate the syndrome |
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| How is Reye's syndrome diagnosed? |
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| Lumbar puncture is first step in a suspected CNS infection, results determine the next step CT and MRI Biopsy of the brain (last resort) |
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| What are lumbar punctures contraindicated? |
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| When intracranial pressure is severely increased |
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| What PMN levels would you expect to find in the CSF during a CNS infection? |
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| Much higher PMNs in bacterial, lower in viral Normal is 0 Viral <50 Pyogenic bacterial >60 Tuberculosis and mycosis <50 |
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| What glucose levels would you expect to find in the CSF during a CNS infection? |
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| Unchanged if viral, lowered if bacterial or fungal |
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| What protein levels would you expect to find in the CSF during a CNS infection? |
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| Slightly increased if viral (30-80), much higher if bacterial or fungal (>60) |
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| How is bacterial meningitis confirmed? |
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| Culture - isolation from CSF or blood Latex agglutination test for Crypto, Strep pneumo, Neisseria, and H. influenza Gram stain |
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| What are the clinical findings/symptoms in bacterial meningitis? |
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| Acute onset of fever and headache Either neck stiffness or altered consciousness or both |
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| What types of meningitis cannot be differentiated on clinical grounds alone? |
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| Hib, meningococcal meningitis and pneumococcal meningitis |
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| What lab findings increase the probability of a patient having bacterial meningitis? |
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| Turbid appearance Leukocytosis (> 100 cells/mm3)or Leukocytosis (10-100 cells/ mm3) AND either an elevated protein (> 100 mg/dl) or decreased glucose (< 40 mg/dl) |
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| How is meningitis treated |
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| Antimicrobials (unless it's viral), course varies from days if uncomplicated bacterial to a year for tuberculous meningitis and several years in some cases of fungal meningitis Correct metabolic defects if any Monitor and control intracranial pressure Supportive treatment if viral (except HSV which responds to early antiviral treatment) |
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| What are the general characteristics of Neisseria meningitidis? |
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| Gram neg cocci, appears in pairs Kidney bean appearance Transmitted via inhaled respiratory droplets Humans are only host |
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| Neisseria meningitidis can be cultured on what mediums? |
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| Blood agar and Chocolate agar |
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| What are the important serotypes of Neisseria meningitidis? |
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| A, B, C, W-135, and Y 50% of cases are caused by B which is the serotype absent in the vaccine |
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| Which Neisseria meningitidis serotype is historically associated with epidemic outbreaks? |
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| A |
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| What are the virulence factors of Neisseria meningitidis? |
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| Meningococcal polysaccharide capsule IgA protease LPS/LOS |
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| What inhibits opsonin-mediated phagocytosis in Neisseria meningitidis? |
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| Meningococcal polysaccharide capsule |
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| How does Neisseria meningitidis avoid ciliary activity in order to escape host mucosal defenses? |
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| Secretes IgA protease |
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| How does Neisseria meningitidis cause endotoxemia? |
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| Cytokines are released by leukocytes in rsponse to LPS (LOS), causing damage to blood vessels and vascular collapse, hemorrhaging, and petechiae on the trunk and appendages Similar to toxic shock syndrome |
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| How does Neisseria meningitidis cause intense subarachnoid inflammation? |
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| Is in response to cytokines secreted due to virulent factors N. meningitidis is the only gram neg bacteria that does not need to die to release LPS and can do so while replicating |
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| How does Neisseria meningitis manifest? |
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| Acute purulent meningitis is the most frequent Meningococcemia without meningitis can progress to fulminant DIC and shcok as well as destruction of the adrenals glands (Waterhouse-Frederichson syndrome) |
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| How is Neisseria meningitis diagnosed? |
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| Culture of CSF, blood, or skin lesions of Neisseria meningitidis on chocolate or blood agar for 12-18hrs |
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| What age group is most susceptible to Neisseria meningitidis? |
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| Children between 6-24mo due to the disappearance of the maternal antibody |
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| How is Neisseria meningitis prevented? |
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| Vaccine against serogroup A, C, and W135 are available Not long lasting, not effective under 2yo Prophylaxis with rifampin for exposed individuals |
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| How is Neiserria meningitis treated? |
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| Penicillin due to good CSF penetration If resistant, use 3rd gen cephalosporin |
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| What are the general characteristics of Streptococcus agalactiae (aka group B strep)? |
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| ? Gram positive cocci arranged in short chains and diplococcal pairs ? Facultative anaerobes B-hemolytic (less distinct than GAS) or non-hemolytic Classified by group specific carbohydrate (B antigen) on cell wall, type-specific polysaccharide antigens in capsule, and surface protein (C protein) |
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| How does Strep agalactiae infect newborns? |
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| Gains access tot he amniotic fluid or colonizes newborns passing the brith canal |
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| What serotypes of Strep agalacitae are most commonly associated with neonatal disease? |
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| Ia III (only unique one from adults) V |
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| What serotypes of Strep agalacitae are most commonly associated with adult disease? |
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| Ia V |
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| What is the primary virulence factor of Strep agalactiae? |
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| GB capsule, prevents opsono-phagocytosis |
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| What defines early onset Strep agalactiae infections? |
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| Disease in infants younger than 7 days |
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| What defines late onset Strep agalactiae infections? |
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| Disease appearing between 1 week and 3 months of age |
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| When are meningitis and focal infections in the bones and joints in cases of GBS infections in infants more likely? |
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| When they are late onset (between 1 week and 3 months of age) |
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| When are high fever, headache and neck stiffness in cases of GBS infections in infants more likely? |
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| When they are older than 2yo |
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| How does a GBS infection in adults generally present? |
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| 2 groups: The first are peripartum chorioamnionitis and bacteremia Other infections include pneumonia and a variety of skin and soft tissue infections May be serious but usually not fatal unless immunocompromised Not associated with rheumatic fever or acute glomerulonephritis |
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| How is GBS diagnosed? |
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| Culture in blood agar produces small beta-hemolytic colonies Confirmed via bacitracin sensitivity and CAMP test Can also do determination of the Lancefield group (definitive identification) |
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| How does GBS present on a CAMP test? |
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| Produces a characteristic arrowhead area of hemolysis at the junction of S. aureus and S. agalectiae streaks on blood agar |
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| How are GBS infections treated? |
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| Although penicillin is the treatment of choice, GBS are slightly less susceptible to b-lactams than other streptococci Neonatal infections are usually treated with treated with combinations of penicillin (or ampicillin) and an aminoglycoside |
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| How is neonatal GBS infection prevented? |
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| Screen birth canal for colonization in 3rd trimester Assign risk on clinical grounds (eg, prematurity, prolonged membrane rupture, fever) |
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| What is the only gram positive diplococcus? |
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| Strep pneumoniae |
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| What is the distinguishing structural feature of Strep pneumoniae? |
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| Its capsule |
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| How is Strep pneumoniae cultured? |
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| On blood agar, produces round, glistening colonies surrounded by a zone of a-hemolysis |
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| Why do S. pneumoniae colonies have a tendency to undergo autolysis? |
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| Due to their susceptibility to peroxides produced during growth and the action of autolysins, a family of pneumococcal enzymes that degrade peptidoglycan |
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| Autolysis of S. pneumoniae is accelerated with what? |
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| Bile salts |
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| How is S. pneumoniae differentiated from from S. viridans (another a-hemolytic streptococcus)? |
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| Optochin sensitivity or by bile solubility tests |
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| How is S. pneumoniae infection prevented? |
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| Vaccine recommended for elderly due to their susceptibility Conjugate vaccine is available to children (not as comprehensive) |
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| How are S. pneumoniae infections treated? |
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| ? Penicillin and its derivatives Macrolides (penicillin resistant strains) Sulphamethoxazole-trimethoprim (in macrolide resistant strains) Ketolides (when resistant to all other antibiotics) |
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| How does S. pneumoniae avoid immunity? |
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| Too many serotypes |
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| What are the characteristics of Listeria monocytogen? |
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| Gram-positive bacterium; morphology ranges from coccobacilli to long filaments in palisades formation Produces catalase, flagella gives tumbling motility |
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| What is unique about Listeria monocytogen growth? |
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| Can grow at 4 C, unique to non-spore forming bacteria |
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| Why is Listeria monocytogen a concern for pregnant women? |
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| Can cross the placenta, produces widespread abscess in tissues of the fetus Avoid deli meats and cheese |
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| How is Listeria monocytogen most commonly contracted? |
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| Ingestion of contaminated dairy products, poultry and meat (cold growth enhances infectivity) |
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| What are the virulence factors of Listeria monocytogen? |
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| Internalin Listerolysin O (LLO) |
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| Listeria monocytogen has what kind of characteristic movement? |
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| "Like a comet through the evening sky” |
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| What is the function of internalin secreted by Listeria monocytogen? |
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| Bacterial surface protein, induce reorganization of host cell cytoskeleton with formation of a vacuole, within which Listeria enters the cell |
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| What is the function of Listerolysin (LLO)? |
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| Aids escape of Listeria to the cytosol |
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| How does Listeria gain a tail? |
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| In the cytosol using cellular actin filaments |
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| Listeria has a tropism for what? |
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| CNS; seeding of bacteria into the brain and its meninges cause encephalitis and/or meningitis |
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| How does Listeria monocytogen infection manifest in adults? |
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| Fever, headache, stiff neck, vomiting, impaired consciousness, convulsions Abd pain, diarrhea, fever, nausea In immunocompetent: fever, malaise, septicemia and meningitis (most common clinical presentation) |
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| How does Listeria monocytogen infection manifest in early-onset neonates? |
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| Granulomatosis infantisepticum in utero transmission; sepsis with high mortality; disseminated granulomas with central necrosis |
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| How does Listeria monocytogen infection manifest in late-onset neonates? |
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| 2–3 weeks after birth from fecal exposure; meningitis with septicemia |
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| Listeria meningitis is most common among what type of patients? |
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| Most common cause of meningitis in renal transplant patients and adults with cancer |
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| What mediates immunity to Listeria? |
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| Both CD4+ and CD8+ T cell subsets are required for resolution and long-lived protection |
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| How is Listeria meningitis diagnosed? |
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| Gram staining of CSF sample reveal Gram-positive rods Culture of CSF or blood specimens produce b-hemolytic colony on blood agar, isolates are gram positive rods (rather than cocci) |
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| How are Listeria infections treated? |
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| Sensitive to penicillin, ampicillin and TSX Fulminant cases are treated with the combination of gentamicin and ampicillin |
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| What is the general appearance of Hemophilus influenza? |
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| Small gram-negative coccobacilli |
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| Hemophilus influenza virulence is dependent on what? |
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| The presence of a capsule (strains type A to F) Capsule inhibits opsonization and phagocytosis Type B is most virulent Pili and other adhesins bind to epithelial cells |
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| Hemophilus influenza grows on what type of media? What does it require for growth? |
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| Chocolate agar Requires hematin (X factor) and NAD for growth Can create satellite colonies when grown with Staphylococcus which lyses RBCs |
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| How does H. influenza tend to manifest differently depending on age? |
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| Children under 2 years of age suffer mostly from meningitis Children of 2-5 years of age suffer from epiglottitis and pneumonia |
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| How is H. influenza diagnosed? |
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| Combination of clinical findings and a typical Gram smear Confirmed by isolation from CSF or from blood Coccobacillus grow on chocolate agar but not blood agar |
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| How is H. influenza infection prevented? |
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| Conjugated vaccine exists, very effective |
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| How are H. influenza infections treated? |
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| Start with a third generation cephalosporin (e.g. ceftriaxone or cefotaxime) May change to ampicillin if susceptibility tests indicate that the infecting strain is susceptible |
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| How is H. influenza immunity mediated? |
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| Anticapsular antibody is generated, which are bactericidal in the presence of complement Infants are protected by maternal antibody up to 6 months of age Antibody response to Hib PRP is poor in children less than 18 months of age |
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| What causes Hansen's disease (Leprosy)? |
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| Mycobacterium leprae |
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| What are the physical characteristics of Mycobacterium leprae? |
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| Identical to M. tuberosis in morphology, structure, and staining Aerobic, acid-fast, rod stains in beads |
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| How is Mycobacterium leprae cultured? |
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| Does not grow in culture but in living cells Very slow growth (12-14day generations) |
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| Mycobacterium leprae grows within what type of cells? |
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| Within macrophages and Schwann cells Humans are the only reservoir |
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| What are the virulent factors of mycobacterium leprae? |
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| Mycoside Phenolic Glycolipid (PGL-1) Lipoarabinomannan (LAM) |
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| What are the manifestations of tuberculoid leprosy? |
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| Areas of macule or large flattened plaques on the face, trunk, and limbs Edges are raised and erythematous, dry, pale, hairless Gradually becomes anesthetic when bacterium invades peripheral nerves Peripheral nerve involvement is characteristic, will often become thickened and visible, leads to numbness |
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| Biopsies of peripheral nerves infected with tuberculoid leprosy usually show what? |
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| Non-caseating epithelioid granuloma with lymphocytic reactions |
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| What causes lepromatous leprosy? |
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| Uncontrolled Mycobacterium leprae growth due to a lack of or suppressed CMI and DTH Histology/biopsy shows bacteria and lymphoyctes with little macrophage activation |
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| What are the manifestations of lepromatous leprosy? |
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| Skin lesions are extensive, symmetric, and diffuse, most obvious on the face: lips, ear, and forehead thickening is classic appearance Loss of finger or toe digits, nasal bone, and nasal septum can occur if severe Spreads systemically via the reticuloendothelial system NO granulomas |
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| How is lepromin used to distinguish tuberculoid and elpromatous leprosy? |
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| Is analogous to tuberculin Tuberculoid: positive lepromin test - minimal disease Lepromatous: negative lepromin test – progressive and severe form of disease |
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| Tuberculoid leprosy induces what type of immune response? |
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| TH1-biased response - causes activation of infected macrophages and control of bacterial growth. Patients usually survive though may suffer from chronic disease |
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| Lepromatous leprosy induces what type of immune response? |
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| TH2-biased response – causes uncontrolled bacterial growth within MQ due to lack of MQ activation, pathogens are inaccessible to Abs Bacilli disseminate and is often fatal |
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| TH1 activates what cytokines? |
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| IL-1 IFN-gamma TNF-beta TH1 response occurs in tuberculoid leprosy |
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| TH2 activates what cytokines? |
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| IL-4 IL-5 IL-10 TH2 response occurs in lepromatous leprosy |
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| How is tuberculoid leprosy treated? |
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| Sulfones block PABA metabolism, combine with rifampin for 6mo(?) |
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| How is lepromatous leprosy treated? |
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| Sulfones, rifampin, and clofazimine for at least 2yrs |
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| Tuberculous meningitis is most common among what demographics? |
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| Children and HIV patients |
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| How does tuberculous meningitis present? |
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| May be subtle as headache and mental changes but can also cause acute confusion, lethargy, altered sensorium, and neck rigidity Course is 1-2wks, longer than bacterial meningitis Often seen with paresis of cranial nerves, most often ocular nerves Focal ischemia if it involves cerebral arteries is a risk, hydrocephalus is common |
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| What is the general appearance of Mycobacterium tuberculosis? |
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| Slender acid-fast, rod shaped bacterium, no spore |
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| What is unique about the cell wall of Mycobacterium tuberculosis? |
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| Unlike other Gram-positive bacteria, it contains N-glycolyl muramic acid rather than N-acetylmuramic acid Highly resistant to drying, disinfectants, and strong acids/alkalis due to its hydrophobic lipid surface |
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| What are the virulent factors for Mycobacterium tuberculosis? |
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| Mycolic acid Mycosides Sulfolipids Lipoarabinomannan (LAM) – analogous to LPS in gram neg bacteria |
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| How is Mycobacterium tuberculosis diagnosed? |
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| Colonized on Lowenstein-Jensen medium, shows granular waxy growth, very long generation time (>12hrs) Fluorescent staining shows yellow-green fluorescent thin rods Ziehl-Neelson stain shows red rods |
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| What is a Tuberculoma? |
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| An uncommon manifestation of tuberculosis One or more space-occupying CNS lesions, usually causes seizures & focal signs Biopsy is necessary for diagnosis |
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| How does tuberculosis meningitis present? |
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| Typical caseation is visible on stains Presents with: seizures, fever, listlessness, loss of appetite, severe headache, nausea and vomiting, stiff neck, photophobia, loss of consciousness MRI shows presence |
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| How is tuberculosis meningitis diagnosed? |
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| Lumbar puncture is cornerstone. CSF reveals: High leukocyte count High protein count of 1-8g/L (100-800mg/dL) Low glucose However, any of these can be within normal range Culture of CSF is diagnostic in up to 80% |
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| How do you evaluate a PDD skin test? |
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| >5mm in HIV+ or anyone with recent TB exposure >10mm in high risk population, IV drug abusers, etc. >15mm in low risk populations |
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| What is first line in the treatment of tuberculosis? |
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| Isoniazid (INH) Ethambutol Rifampin Treated with adjunctive glucocorticoids (such as dexamethasone) for faster resolution of CSF abnormalities and elevated CSF pressure Pyrazinamide Streptomycin |
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| How is tuberculosis meningitis treated? |
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| INH, rifampin, ethambutol and pyrazinamide - 2 mo (bactericidal phase) INH and rifampin – 4 mo (sterilization phase) |
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| What is the primary concern when treated tuberculosis? |
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| Compliance Irregular intake gives rise to resistant strains of TB bacillus |
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| What is the general physical appearance of Nocardia? |
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| Strict aerobic Gram-positive rods that form branched hyphae in tissue and culture |
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| Which species of Nocardia are the most commonly involved in human infections? |
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| N. asteroides and N. brasiliensis |
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| N. asteroides and N. brasiliensis grow on what culture medium? |
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| On blood and chocolate agar with white or orange dry, wrinkled colonies Branching pattern of hyphae growth is indicative |
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| N. asteroides and N. brasiliensis tend to have what differing patterns of infection? |
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| Majority of Nocardia pulmonary and brain infections are due to N. asteroides N. brasiliensis is involved with the cutaneous form |
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| How does Nocardia avoid death by phagocytosis? |
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| Most likely by disrupting acidification of phagosomes or by resisting the oxidative burst |
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| How do Nocardia infections present clinically? |
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| Recent history of pneumonia with focal CNS signs Headache, fever, focal neurologic deficit, seizures, nausea, vomiting Primary lesions in the lung show acute inflammation with suppuration and destruction of parenchyma |
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| How is Nocardia infection treated? |
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| Sulfonamide antibiotics Amikacin, imipenem and broad-spectrum cephalosporins are also effective Therapy should be continued for a longer period of time (about 6 weeks) in order to prevent diseminated infection |
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| What causes botulism? |
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| Clostridium botulinum - a gram pos spore forming anaerobe Endospores are highly resistant to heat, can be killed by autoclaving |
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| Which strains of Clostridium botulinum are responsible for human botulism? |
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| A, B, E, and F strains |
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| Botulism is associated with what practice? |
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| Improperly canned foods |
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| What type of toxin is secreted by Clostridium botulinum? |
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| Heat labile C. botulinum exotoxin (neurotoxin + AB toxin) are absorbed into the blood from the intestine |
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| What is the MoA of botulinum toxin? |
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| Prevents the attachment of neurotransmitter vesicle to the cytoplasmic membrane of the nerve cells |
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| What are the different types of botulism? |
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| Intestinal - due to ingestion Wound - dirty wounds or dead tissue can be colonized. Bacteria does not invade tissues but toxins diffuse into the blood |
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| How is botulism treated? |
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| Administration of antitoxin (iv) ASAP Stomach wash and enema to remove any unabsorbed toxin Cleaning and surgical debridement of the wound Supportive treatment including artificial respirations |
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| What are the symptoms of viral meningitis? |
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| Fever, headache, nuchal rigidity Photophobia Myalgias Vomiting Rash |
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| What are the symptoms of bacterial meningitis? |
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| Fever, headache, neck stiffness, nuchal rigidity, meningismus Vomiting, nausea, photophobia, seizures Coma, lethargy, stupor, myalgia Unilateral cranial nerve abnormality Dilated, non-reactive pupil(s) Posturing: decorticate/decerebrate |
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| What does a Meningoencephalitis panel screen for? |
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| Herpes Simplex Virus 1/2 Lymphocytic Choriomeningitis Virus California Serogroup Viruses West Nile Virus Eastern and Western Equine Encephalitis Virus St. Louis Encephalitis Virus |
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| What are the the expected CSF findings in a viral meningitis infection? |
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| Pleocytosis with lymphocyte predominance (neutrophils may predominate early) Pressure: 200-250 mmHg (higher) WBC: 100-1000/mL (<5) Increased protein Decreased or normal glucose Negative gram stain or culture |
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| What type of cells are most dominantly present in cases of viral meningitis? |
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| Lymphocytes (neutrophils may predominate early) |
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| What are the the expected CSF findings in a bacterial meningitis infection? |
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| Pressure: 100-200 mmHg (80-180) WBC: >1000/mL Neutrophil predominance (80%) Gram stain positive 60-90% Protein: <200mg/dL (15-60) Glucose: <40 mg/dL (45-80) |
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| What type of cells are most dominantly present in cases of bacterial meningitis? |
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| High WBCs, predominately Neutrophils |
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| What is the most common cause of viral meningitis? |
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| Enterovirus (includes Coxsackievirus, echovirus, etc) |
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| What are the California serogroup viruses? |
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| Belongs to the Bunyaviridae family La Crosse virus California encephalitis virus Jamestown canyon virus Snowshoe hare virus |
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| What is distinct about the detection of California serogroup viruses? |
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| Not recoverable in CSF during acute phase |
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| What are the characteristics of encephalitis due to a measles (Paramyxoviridae family) infection? |
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| Insidious onset of personality change Poor school performance Progressive intellectual deterioration Development of myoclonic jerks (periodic muscle spasms) Motor dysfunctions |
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| What are the unique characteristics of chronic encephalitis due the measles? |
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| Subacute sclerosing panencephalitis (SSPE) Occurs about 7 years after infection with measles, mainly in those infected before 2yo |
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| Meningitis most commonly occurs in mumps infections (Paramyxoviridae family) when what other symptoms are present? |
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| Occurs in 1-10% of cases that also present with parotitis (which is 30-40% of all mumps infections) Cases without parotitis are indistinguishable from other viral meningitis cases |
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| What are the characteristics of meningitis due to Lymphocytic choriomeningitis virus (LCMV)? |
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| Uncommon infection Lasts 1-3 weeks, but 15% have biphasic symptoms with meningeal signs and more prominent headache in second phase |
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| How does meningitis due to HIV infection usually present? |
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| Initial infection is symptomatic in 40-90% of cases, but often overlooked Usually a mono-like syndrome May present as aseptic meningitis, or less commonly as an encephalitis or cranial nerve palsies |
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| How is viral encephalitis best detected? |
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| MRI (shows better than meningitis infections) |
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| What is the most common cause of viral encephalitis? |
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| HSV |
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| What are the symptoms of HSV induced viral encephalitis? |
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| Altered consciousness >fever >headache >disorientation >behavior or personality changes >seizures |
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| What distinguishes the strains of HSV that cause viral encephalitis? |
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| HSV-1 more likely in sporadic encephalitis HSV-2 more common in recurrent benign lymphocytic meningitis |
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| What are the unique characteristics of viral encephalitis caused by West Nile Virus? |
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| 50% of cases show neutrophil predominance in CSF instead of lymphocytes Unique symptoms (20-40% of cases) include: tremors, parkinsonism, and myoclonus Can cause poliomyelitis like paralysis |
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| St. Louis encephalitis virus is most likely to cause encephalitis among what demographic? |
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| Predominant in those over 60yo In younger, meningitis is almost just as common |
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| What is a common complication of St. Louis encephalitis virus? |
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| Seizures occur in 47% of patients |
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| What are the characteristics of encephalitis caused by Eastern/Western encephalitis virus |
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| Prodrome (malaise, fever, chills, myalgias) is followed by recovery or encephalitis symptoms Mortality is 33% (EEEV) except in those over 60 (50%) Western disease is more mild than Eastern |
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| How does Rabies virus infect humans? |
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| Animal bites introduce virions in saliva which invade motor & sensory nerves |
question
| How long does Rabies virus lay dormant? |
answer
| Can incubate anywhere from 7 days to greater than 6 years (median is 1-2 months) |
question
| What are the characteristics of "furious" rabies? |
answer
| 80% of cases Hyperactivity with hydrophobia and aerophobia due to spasms of pharyngeal and nuchal muscles Spasms increase followed by hallucinations, agitation, autonomic hyperactivity, and seizures Body temp may be as high as 107 |
question
| What are the characteristics of "dumb" rabies? |
answer
| 20% of cases Paresthesias, weakness, and flaccid paralysis in the bitten limb |
question
| What is abortive poliomyelitis? |
answer
| Nonspecific febrile illness caused by poliovirus for 2-3 days without CNS involvement |
question
| What are the symptoms of asceptic meningitis due to poliovirus (nonparalytic poliomyelitis)? |
answer
| Signs of meningeal irritation (stiff neck, pain and stiffness in the back) in addition to the signs of abortive poliomyelitis Rapid and complete recovery within a few days |
question
| How does paralytic poliomyelitis progress (usually less than 2% of the infections)? |
answer
| Starts as a minor illness followed by signs of meningeal irritation along with asymmetric flaccid paralysis with no significant sensory loss In severe cases, all four limbs may be paralyzed, involvement of respiratory muscles is life threatening Recovery of affected neurons may take as long as 6mo Severity increases with age at infection |
question
| What are the basic problems with transplantation therapy? |
answer
| Transplants must be introduced to allow them to perform normal function, health of recipient and transplant must be maintained during surgery, recipient immune system must be prevented from developing adaptive immune responses to antigens on grafted tissue |
question
| What are the hallmark of successful transplantation? |
answer
| Matching the tissue type between donor and recipient Successful suppression of the recipient’s immune system to inhibit response to the grafted organ or tissue |
question
| What is an autograft? |
answer
| A graft from one part of the body to another location on the same individual |
question
| What is an isograft? |
answer
| A graft between genetically identical individuals (identical twins) |
question
| What is an allograft? |
answer
| A graft from a genetically dissimilar donor to a recipient of the same species |
question
| What is a xenograft? |
answer
| A graft from a donor of another species |
question
| What is an allorection? |
answer
| Refers to the immune reactions provoked by the alloantigen |
question
| What is an alloantigen? |
answer
| Refers to an antigen that differs between members of the same species (e.g. HLA molecules and blood group antigens) |
question
| What are minor histocompatibility antigens? |
answer
| Allelic forms of normal cellular proteins that happen to be different between donor and recipients; these non-MHC antigens can also induce graft rejection |
question
| What is most commonly responsible for allograft rejection? |
answer
| HLA (MHC) mismatching is generally most important However, multiple minor histocompatibility mismatching can be as severe as HLA mismatching |
question
| Which MHC mismatching causes the most severe rejection in transplants? |
answer
| Mismatching of MHC II (HLA-DQ, DP, DR) often causes more rapid and severe rejection than mismatching MHCI (HLA-A, B, C) |
question
| Which major HLA are considered for matching? |
answer
| HLA A HLA B HLA DR |
question
| Which blood group only has the core structure and therefore are considered universal donors? |
answer
| O blood group |
question
| Which blood group has both antigens and therefore can only be given the same blood group or the O blood group? |
answer
| AB blood group |
question
| How are gut bacteria involved in the production of blood group antibodies? |
answer
| Gut bacteria bear antigens that are similar or identical to the blood group antigens which stimulates the production of Ab against these Ag |
question
| What is a cross-matching test? |
answer
| Refers to a method of direct assessment of reactivity between recipients serum and donors blood cells |
question
| How is tissue typing done via serology? |
answer
| Microcytotoxicity test or lymphocyte cross-matching: patient’s serum is cross-matched with potential donors lymphocytes Tests all HLA loci |
question
| How is tissue typing done via DNA or molecular techniques? |
answer
| Via PCR Tests all HLA loci |
question
| How is tissue typing done via mixed lymphocyte reaction/response? |
answer
| Done with in vitro culture containing blood leukocytes from both donor and recipient For DR (DQ, DP) molecules |
question
| Hyperacute rejection of transplantation is comparable to what type of hypersensitivity? |
answer
| Type III Immune complex deposition cause complement activation in blood vessel wall |
question
| What can causes hyperacute rejection of transplantation? |
answer
| Preexisting antibodies against A, B, O or HLA antigens in the recipient’s serum |
question
| How might someone gain pre-formed anti-HLA Abs? |
answer
| Generation from pregnancy, blood transfusions, or previous tranplantation |
question
| Acute rejection of transplantation is comparable to what type of hypersensitivity? |
answer
| Type IV hypersensitivity Mediates acute rejection via generation of alloreactive effector cells dependent on whether they are presented by MHCI or MHCII |
question
| What is allorecognition? |
answer
| Recognition of the alloantigen by the recipient’s T cells in a direct or indirect fashion. Seen in acute rejection of transplantation |
question
| What is direct allorecognition? |
answer
| HLA Ags presented on the donor APC interacts w/ CD4 and CD8 T cells |
question
| What is indirect allorecognition? |
answer
| Membrane fragments of dead donor APCs are endocytosed by the recipient’s APC, presents peptides to CD4 T cells only by the recipient’s MHC-II APC |
question
| How do CD4 alloreactive cells cause transplant rejection? |
answer
| They migrate in blood to the graft and activate macrophages to exacerbate the inflammation |
question
| How do CD8 alloreactive cells cause transplant rejection? |
answer
| They migrate in blood to the graft and attack the cells in the transplanted tissue directly |
question
| How is acute rejection development significant when it comes to treatment? |
answer
| Develops over a period of days and therefore, unlike hyperacute rejection can be reduced or even prevented |
question
| What causes chronic rejection of transplantation? |
answer
| Likely due to the indirect pathway of allorecognition Recipient dendritic cells process the internalized allogenic HLA and present them to CD4 T cells Helper T cells get activated which then activate B cells Results in anti-HLA 1 and 2 Ab production |
question
| How does chronic rejection of transplantation manifest? |
answer
| Develops over a period of months to years Thickening of vessel walls and narrowing of their lumina Develops into ischemia and loss of function followed by death |
question
| What corticosteroid is most commonly used for transplant patients? |
answer
| Prednisone Needs to be converted to prednisolone to be active Must be combined with others to prevent graft rejection |
question
| What is the MoA of prednisone? |
answer
| Binds to hsp90 in the cytoplasm Receptor binding induces release of hsp90 Receptor/steroid complex enters nucleus and binds to selective genes to induce transcription |
question
| What are the effects of prednisone? |
answer
| Inhibits inflammatory mediators Inhibits inflammatory cell migration Promotes apoptotic death of leukocytes, including lymphocytes |
question
| What is the MoA of Azathioprine? |
answer
| A cytotoxic pro-drug, must be converted to 6-thioinosinic acid which inhibits inosinic acid, an intermediate in the biosynthesis of adenine and guanine Ultimately inhibits DNA replication |
question
| What are the effects of Azathioprine? |
answer
| Damages all the tissue of the body normally active in cell division, especially bone marrow, intestinal epithelium, and hair follicles |
question
| What is the main concern in using Azathioprine as a cytotoxic immunosuppressant? |
answer
| Hepatotoxicity |
question
| What is the MoA of Cyclophosphamide? |
answer
| A cytotoxic pro-drug with a metabolite that alkylates and cross-links DNA molecules Affects normal cell division and transcription Very toxic to the urinary bladder |
question
| What is Cyclophosphamide used for? |
answer
| Both pre- and post-transplant patient therapy Used as an alternative to methotrexate |
question
| Cyclophosphamide has what significant side effect? |
answer
| Very toxic to the urinary bladder |
question
| What is the drug of choice for inhibiting GVHD in bone marrow transplant patients? |
answer
| Methotrexate |
question
| What is the MoA of Methotrexate? |
answer
| Prevents DNA replication by inhibiting dihydrofolate reductase essential for thymidine synthesis |
question
| What is Cyclosporin? |
answer
| Derived from a soil fungus, inhibits T cell activation by antigens by disrupting transduction of signals from TCR resulting in inhibition of IL-2 production and subsequent shut down of the activation, proliferation, and differentiation of T cells |
question
| What is Tacrolimus? |
answer
| Derived from soil actinomycetes, suppresses T cell activation by a similar mechanism as that of cyclosporine (inhibiting IL-2 production to prevent T cell activation) |
question
| What is Rapamycin? |
answer
| Isolated from a soil bacterium, inhibits T cell activation by preventing signal transduction from IL-2 receptors |
question
| What are the antibodies specific for T cells? |
answer
| Antithymocyte globulin (ATG) or antilymphocyte globulin (ALG) are prepared from animals’ blood Abs can also be prepared from hybridoma cell line which produce mouse monoclonal Abs specific for proteins present only on T cell surfaces such as CD3 |
question
| Bone marrow transplantation is most commonly prescribed for what? |
answer
| SCID |
question
| What hematopoietic diseases are treatable with bone marrow transplant? |
answer
| SCID, Fanconi's anemia, thalassemia major, sickle-cell anemia |
question
| How is the preparative phase for bone marrow transplant different from solid organ transplants? |
answer
| The entire immune system will be affected by transplant and therefore, the whole hematopoietic system, including immune system is ablated by combined radiation and immunosuppressive drugs Referred to as myeloablative therapy |
question
| What is the purpose of myeloablative therapy? |
answer
| Prevents rejection of graft cells by recipient T cells Provides room for the transplanted stem cells to interact with bone marrow stromal cells in BMT |
question
| What is required for a successful bone marrow transplant? |
answer
| The donor and recipient should have at least one HLA class I and one HLA class II allotype in common (more is better) |
question
| What causes Graft-versus-Host Disease? |
answer
| Mature T lymphocytes in donor bone marrow recognize tissues of the new host as foreign and cause a severe inflammatory disease in the recipient |
question
| What are the symptoms of acute GVHD? |
answer
| A rash Diarrhea Pneumonitis Liver damage |
question
| What is characterized by chronic GVHD? |
answer
| Fibrosis and atrophy of one or more of the same organs without evidence of cell death If severe, can lead to complete dysfunction of the affected organ, may be fatal |
question
| How does the skin rash seen in bone marrow transplant BMT present? |
answer
| Often starts at the face and neck and then spreads to involve the trunk and limbs A bright red rash that characteristically involve the palm and sole The rashes may cause severe pruritis May be accompanied with fever |
question
| What is histologically distinct in skin rashes in BMT? |
answer
| In early GVHD, lymphocytes emerging from blood vessels adhere to the basal layer of epidermis The basal cells of the epidermis begin to swell and vacuolate; their nuclei become condensed as these cells die |
question
| What is characteristics about GI disturbance in GVHD? |
answer
| Appears after skin manifestation Causes watery diarrhea |
question
| How is the liver affected in GVHD? |
answer
| Infiltrated with inflammatory cells, causes liver enzymes to rise |
question
| What are the different grades of skin rashes in GVHD? |
answer
| I: maculopapular rash on <25% of body II: maculopapular rash on <25-50% of body III: generalized erythroderma IV: generalized erythroderma with bullous formation and desquamation |
question
| What are the different grades of liver damage in GVHD? |
answer
| Based on serum bilirubin I: 2-3 mg/dl II: 3-6 mg/dl III: 6-15 mg/dl IV: 15 mg/dl |
question
| What are the different grades of GI disturbance in GVHD? |
answer
| >500 ml diarrhea/day >1000 ml diarrhea/day >1500 ml diarrhea/day Severe abdominal pain with or without ileus |
question
| Who are the best possible donors for BMT? |
answer
| HLA identical siblings |
question
| Why do some HLA identical siblings still develop GVHD? |
answer
| Occurs particularly in males who receive from sisters. If the specific HLA molecule is on a male-specific Y chromosome, the sister T cells cannot be toleran |
question
| What are minor histocompatibility antigens? |
answer
| Alloantigens in which the allogenic difference is due to the bound peptide and not due to MHC molecule are called minor histocompatibility antigens Encoded by minor histocompatibility loci |
question
| How can minor histocompatibility antigens precipitate GVHD? |
answer
| Self-proteins are routinely digested by proteosomes within the cells cytosol. These proteins are presented on the surface in the context of MHC molecules If a polymorphic protein differs between the graft donor and the recipient, it can give rise to an antigenic peptide that can be recognized by recipient’s T cells as non-self and elicit an immune response |
question
| How does GVHD impart a beneficial effect on leukemia patients? |
answer
| Removal of T cells from the bone marrow graft in the treatment of GVHD leads to increased rates of graft failure and particularly, with cancer, a high incidence of recurring of disease Called graft-versus-tumor or graft-versus-leukemia effect |
question
| What is the purpose of autologous bone marrow transplants? |
answer
| Designed to help patients clinically eligible for BMT unable to find a suitable HLA-matched donor |
question
| What are autologous bone marrow transplants? |
answer
| Samples of patients own bone marrow are taken before the remainder is destroyed by irradiation and immunosuppressive therapy The stem cells are separated from the tumor and other cells and are reinfused to the patient |
question
| What are the limitations of autologous bone marrow transplants? |
answer
| Frequent relapse of cancer compared to allogenic transplant |
question
| What is a hematopoietic stem cell transplant? |
answer
| Donor is treated with G-CSF and GM-CSF to mobilize hematopoietic stem cells to the peripheral blood from the bone marrow Leukocytes are selectively removed from the blood by a process called leukapheresis where the CD34 positive stem cells are isolated and used as transplant The other source of hematopoietic stem cells is umbilical cord cells obtained from placenta after birth |
question
| How many cells are required to perform a hematopoietic stem cell transplant? |
answer
| 0.25 to 0.5 billion cells are required for prompt engraftment after transplantation |
question
| What are the Transmissable Spongiform Encephalopathies (TSE)? |
answer
| Creutzfeld-Jakobs Disease (CJD) Bovine Spongiform Encephalopathy (BSE) Kuru (humans), scrapie (sheep) Chronic wasting disease (CWD) |
question
| What are normal, healthy prions (PrPc)? |
answer
| Product of PRNP gene on chromosome 20 Glycoprotein anchored to cell membrane Well-conserved in most mammalian species Predominantly expressed in neuronal cells |
question
| What is the function of normal healthy prions (PrPc)? |
answer
| Maintenance of neuronal integrity in the brain Possible role in Cu metabolism & cellular response to oxidative stress |
question
| What are the characteristics of aberrant PrPsc? |
answer
| Resistant to proteolysis Insoluble in nondenaturing detergents |
question
| What how are aberrant prions (PrPsc) formed? |
answer
| Conformation change from a predominantly ?-helical structure to predominantly ?-sheets Endogenous PrPc interacts with PrPsc, converts PrPc to PrPsc, can begin spontaneous generation |
question
| What are the symptoms of prion disorders (Transmissable Spongiform Encephalopathies)? |
answer
| Personality changes, depression Lack of coordination - jerky movements Insomnia, confusion, memory problems Severe mental impairment and inability to move or speak in later advanced stages Vacuolization of neuronal cytoplasm results in sponge-like appearance of brain parenchyma |
question
| What is Kuru? |
answer
| Restricted to the highlands of New Guinea Ritualistic cannibalism lead to spreading of spongiform encephalopathies (prion diseases) due to brain tissue being highly infectious |
question
| What is the most common parasitic infection of the CNS? |
answer
| Toxoplasma gondii |
question
| How is Toxoplasma gondii most commonly contracted? |
answer
| Ingestion of tissue cysts in undercooked meat Primary hosts are cats |
question
| What are the 3 infectious stages of Toxoplasma gondii? |
answer
| Tachyzoites (rapidly multiply in any cell, see in acute infection, released when organism is ingested) Bradyzoites (found in tissue cysts, multiply slowly in chronic stages) Sporozoites (found in oocysts, shed in feces) |
question
| What type of people are more susceptible to Toxoplasma gondii infection? |
answer
| Immune response normally neutralizes and removes tachyzoites Immunocompromised at heightened risk, can cause necrotizing encephalitis |
question
| What are the symptoms of Toxoplasmosis? |
answer
| Fever, malaise, night sweats, sore throat Retroperitoneal & mesenteric lymphadenopathy Chorioretinitis CNS disease in 50% of infected immunocompromised patients |
question
| What are the complications of congenital toxoplasmosis? |
answer
| Severe if maternal infection occurs early in pregnancy May cause CSF pleocytosis & elevated protein levels Microcephaly Affected survivors may have mental retardation, visual defects, seizures |
question
| What is the deadliest complication of Plasmodium falciparum (malaria)? |
answer
| Cerebral malaria The major cause of death from malaria |
question
| What are the symptoms of cerebral malaria? |
answer
| Encephalitic syndrome Ataxia, seizures, hemiplegia, coma, death Parasitized RBCs are sequestered in the cerebrum, cerebellum, and medulla oblongata, causes compensatory vasodilation, increased brain volume |
question
| Cerebral malaria patients who have undergone successful parasitic treatment can still retain what negative effects? |
answer
| Can still retain residual neurological damage Memory, learning, and language impairments Visuospatial and motor deficits Psychiatric disorders |
question
| Describe the life cycle of Plasmodium falciparum |
answer
| Travel to the liver, replicate into merozoites Merozoites leave the liver and invade RBCs Continue to replicate, lyse RBCs, and invade other RBCs Cycle continues when mosquitos bite an infected human |
question
| What causes RBC Rosettes? What are they? |
answer
| RBC rosette-forming P. falciparum Parasitized RBC surrounded by 3 or more uninfected RBCs Interaction appears to be mediated by knobs seen on the parasitized RBC |
question
| What is Naegleria fowleri? |
answer
| Thermophilic, free-living amoeba seen in waterways contaminated by thermal discharge of powerplants, heated swimming pools, hot springs (up to 45degC) Inhabits fresh water ponds, lakes, rivers |
question
| How does Naegleria fowleri cause primary amebic meningoencephalitis (PAM)? |
answer
| Amebic-contaminated water enters the nose during activities such as swimming Migrates to the brain through the olfactory nerve from the olfactory mucosa Rare, but nearly always fatal infection Symptoms arise around 2-3 to up to 7-15 days after infection |
question
| What are the symptoms of amebic meningoencephalitis (N. fowleri)? |
answer
| Early symptoms: Upper respiratory distress, headache, lethargy, olfactory problems Sore throat, stuffy, blocked, or discharging nose, severe headaches Pyrexia, vomiting, stiffness of neck are also possible Mental confusion, coma occur about 3-5 days before death Symptoms indistinguishable from bacterial meningitis |
question
| What is the most common cause of death due to amebic meningoencephalitis (N. fowleri)? |
answer
| Cardiorespiratory arrest and pulmonary edema |
question
| Describe the pathophysiology and virulence of Naegleria fowleri |
answer
| High oxygen content of CSF and brain tissue enhances growth due to containing mitochondria Ingests RBCs and brain tissues to cause severe hemorrhagic necrosis, produces an amebostome (food cup) and secretes lysosomal hydrolases and phospholipases Produces and secretes heat stabile hemolytic proteins, heat-labile cytolysin, phospholipase A, cysteine protease Presence of protein and glucose in CSF supports N. fowleri |
question
| How is Naegleria fowleri diagnosed? |
answer
| Spinal tap ASAP shows: Elevated protein Normal or slightly reduced glucose levels WBC high (400-26000/?L) RBC high Wet mount positive for motile trophozoites Smears can be stained using Wright’s/Giemsa stain |
question
| How is Naegleria fowleri treated? |
answer
| Early diagnosis is essential due to rapid course of infection Near immediate chemotherapy is essential for survival |
question
| What is the characteristic feature of Acanthamoeba? |
answer
| The presence of spine-like pseudopods called acathapodia |
question
| How are Acanthamoeba infections contracted? |
answer
| Primary entry sites are the skin and lungs Usually repelled using humoral immunity and complement activation Patients tend to have no history associated with exposure to recreational freshwater |
question
| What are the consequences of unsuppressed Acanthamoeba infections? |
answer
| Causes granulomatous amebic encephalitis (GAE) Primarily in immunosuppressed or chronically ill patients Route of invasion is believed to be hematogenous Causes CNS lesions with trophozoites and cysts |
question
| What are the risk factors for granulomatous amebic encephalitis (GAE) due to Acanthamoeba infection? |
answer
| Chronically ill, immunologically impaired, Malignancies, SLE, HIV, Hodgkin’s, DM Infections are associated with trauma and underlying disease |
question
| What is Trypanosoma brucei gambiense? |
answer
| West African trypanosomiasis Exclusively human reservoir Slow-progressing that can be self-limiting or develop into a chronic disease involving the CNS and lymphatic system |
question
| What is Trypanosoma brucei rhodesiense? |
answer
| East African (or Rhodesian) trypanosomiasis Zoonotic disease (animal reservoir) Rapidly progressing disease |
question
| What are kinetoplastids? |
answer
| Potentially infectious mitochondrial DNA (?) |
question
| Describe the progression of African Sleeping Disease (Trypanosomiasis) |
answer
| 1-2 wk incubation period Acute blood stage: fever, headaches Invades lymphatics, causes lymphadenopathy, weight loss, weakness, rash, itching, intermittent febrile attackes Relapses due to antigenic variation of trypanosomal surface Nervous System Impairment: 6-12mo w/ gambiense, w/in weeks w/rhodesiense |
question
| What happens when Trypanosomes (African sleeping disease) crosses the blood brain barrier? |
answer
| Meningoencephalitis Apathy, fatigue, confusion, motor changes (tics, slurred speech) Changed sleep patterns: Extreme fatigue during day, extreme agitation during night If untreated, can progress to coma or death |
question
| Taenia solium is most commonly contracted through what means? |
answer
| Eggs ingested from poorly cooked pork, hatch in the stomach |
question
| What are the symptoms of neurocystercercosis? |
answer
| Larvae attach either to brain tissues or the cavities through which the brain fluid flows, develop into cyst-like structures Seizures, altered mental states, headache, nausea, dizziness, can block flow of brain fluid |
question
| How does Taenia solium avoid the immune system? |
answer
| Brain not easily accessible to immune cells due to the BBB Cysts are able to degrade antibodies made to it Produces protein signals that inhibit phagocytosis |
question
| What is Echinococcus granulosus? How is it contracted? |
answer
| Zoonotic tapeworm infection Dogs are the definitive hosts, humans are accidental, intermediate hosts Eggs are ingested and hatch in small intestine High risk: own/live with dogs used to herd sheep Transmission enhanced by feeding dogs raw viscera of slaughtered livestock |
question
| How does Echinococcus granulosus progress? |
answer
| Eggs hatch, penetrate gut wall, and enter circulation Larvae can be distributed almost anywhere in the body. Most common site is the liver but brain can be infected as well Develop into hydatid cysts over about 5 months |
question
| What are the characteristics of hydatid cysts (Echinococcus granulosus)? |
answer
| An outer, friable, nonnucleated layer And an inner, nucleated germinal layer Daughter cysts bud off from the inner germinal layer Later detach and float in the interior of the fluid filled cyst Organized as unilocular cysts |
question
| How is Echinococcus granulosus treated? |
answer
| Surgical removal if cysts are accessible Cysts injected with anti-protoscolicidal agent to reduce chance of leakage of anaphylactogenic or infectious contents during surgery Sensitive to Praziquantel |
question
| What is the most common cause of human eosinophilic meningitis? |
answer
| Cerebral Angiostrongyliasis (Angiostrongylus cantonensis) |
question
| How are Angiostrongylus cantonensis infections contracted? |
answer
| Human infection due to accidental ingestion of infective larvae Slugs, snails, raw fish, amphibians, reptiles, crustaceans, seafood Vegetables contaminated with larvae Infected water Oral contact with hands contaminated with mollusk larvae Sometimes through the skin |
question
| What are the symptoms of Cerebral Angiostrongyliasis? |
answer
| Due to presence of larvae in the brain and the host response Severe headaches, convulsions, weakness of limbs, facial paralysis, neck stiffness, fever Vomiting, constipation, anorexia, nausea Pulmonary symptoms usually absent Sometimes, ocular invasion Incubation period approximately 20 days |
question
| How is Cerebral Angiostrongyliasis diagnosed? |
answer
| CSF analysis shows Elevated pressure Elevated protein levels Presence of leukocytes: 100-2000/mm3 Eosinophilia Often peripheral eosinophilia with moderate leukocytosis Larvae, or young adult worms can be recovered in the CSF Elevated IgG, IgA, IgM, IgE CT scan shows brain lesions |
question
| What is Cryptococcus neoformans? |
answer
| Encapsulated yeast-like fungus Under certain environmental conditions, is capable of forming mycelia Usually grows as a yeast with a prominent capsule Found in soil contaminated with pigeon droppings Most common clinical form is meningoencephalitis |
question
| What are the virulence factors of Cryptococcus neoformans? |
answer
| Polysaccharide capsule Ability to grow at 37 degC Phenol oxidase enzyme prevents formation of toxic hydroxyradicals and oxidative stress |
question
| What are the symptoms of meningoencephalitis due to Cryptococcus neoformans? |
answer
| Antigen in the CSF can potentially change the osmolality affecting flow and absorption Increases intracranial press Headaches, vision loss, early death |
question
| What is Coccidioides immitis infection (coccidiodomycosis) and how is it contracted? |
answer
| True, systemic mycosis Acquired by inhalation - dry arthroconidia carried by dust storms Related to activities involving tillage of soil (agriculture, archaeology, telephone post digging) Seen in the southwest US, thrives in warm, dry soils Initially presents as a pulmonary infection that can disseminate to other organs |
question
| What are the symptoms of CNS disseminated Coccidioides immitis (coccidiodomycosis)? |
answer
| Chronic granulomatous meningitis in the basilar meninges, cerebral and cerebellar abscesses, headache, nausea, vomiting, altered mental status Intense immunologic rashes when disseminated |
question
| What is the most lethal form of coccidioidomycosis? |
answer
| Dissemination to the CNS causes chronic granulomatous meningitis (basilar meninges), cerebral and cerebellar abscesses. Causes headache, nausea, vomiting, altered mental status |
question
| What are Tumor-Specific Transplantation Antigens (TSTA)? |
answer
| Unique to tumor cells and not expressed on/in normal cells Responsible for rejection of tumor |
question
| What are Tumor Associated Transplantation Antigens (TATA)? |
answer
| Antigens expressed by both tumor and normal cells May have higher expression in tumor cells or may be cease expression by normal cells as adults and re-expressed in tumors |
question
| Which tumor antigen is considered a product of mutated genes or oncogenic virus genes? |
answer
| Tumor-Specific Transplantation Antigens (TSTA) |
question
| Which tumor antigen is considered to be a product of abnormal expression of normal genes? |
answer
| Tumor Associated Transplantation Antigens (TATA) |
question
| Tumor Associated Transplantation Antigens (TATA) are composed of what normally expressed antigens? |
answer
| Oncofetal antigens Altered glycolipid and glycoprotein antigens Tissue-specific differentiation antigens |
question
| What is the consequence of gene mutations producing new antigens? |
answer
| A change in the sequence changes what peptides can be presented. This can also be caused by oncogenic viral infection |
question
| Papilomavirus has been linked to the development of which associated tumors? |
answer
| Benign warts Carcinoma of the uterine cervix |
question
| HBV has been linked to the development of which associated tumors? |
answer
| Liver cancer/hepatocellular carcinoma |
question
| EBV has been linked to the development of which associated tumors? |
answer
| Burkitt's lymphoma Nasopharyngeal carcinoma B-cell lymphoproliferative disease |
question
| HIV and HHV8 have been linked to the development of which associated tumors? |
answer
| Kaposi's sarcoma |
question
| What is the consequence of expression of fetal proteins in tumor cells? |
answer
| Allows the presentation of peptides the majority of the immune system has never seen |
question
| How many MHC:peptide complexes are required on a target cell to activate a T cell? |
answer
| 10-100 identically loaded MHC;Peptide complexes Without a costimulatory receptor (CD4 or CD8), it would take 10,000 |
question
| What are tissue-specific differentiation antigens? |
answer
| Cell surface markers or intracellular proteins/receptors that are found only on/in specific lineages of cells (ex. CD4 on T cells or CD10/CD20 on B cells) |
question
| What are the abnormal cell surface antigens continually secreted by most human tumors? |
answer
| Gangliosides (GM2, GD2, GD3) Blood group antigens Mucins |
question
| What abnormal markers are recognized by NK cells? |
answer
| Altered cell-surface glycoproteins Loss of class I MHC Bound antibodies |
question
| How do NK cells facilitate killing targeted cells? |
answer
| Release of cytotoxic granules |
question
| Activation and killing by NK cells is dependent on what factor? |
answer
| The extent of inhibitory and activating receptors being used. If there are more activating than inhibitory, the NK cell will be activated |
question
| What are the different protein families of NK cell receptors? |
answer
| NKG2 family (6 members): A and B are inhibitory, C and D are activating Ly49 family: A and G are inhibitor, D and H are activating |
question
| What abnormal markers are recognized by macrophages? |
answer
| Bound antibodies Receptor interactions such as NKG2D receptor expression |
question
| How do macrophages facilitate the killing of targeted cells? |
answer
| Phagocytosis Production of NO |
question
| How do actively replicating tumor cells continue to mutate while growing in number? |
answer
| Each round of replication increases mutations Mutations that increase growth or are silent propagate Mutations that are incompatible with replication lead to apoptosis and engulfment by phagocytic cells |
question
| What is recognized by CD8+ T cells? |
answer
| Tumor antigens presented in class I MHC |
question
| How do CD8+ T cells facilitate the killing of targeted cells? |
answer
| Release of cytotoxic granules Fas receptor ligation |
question
| What is the mechanism of recruitment by Regulatory T-cells (Treg)? |
answer
| Tumor expressed chemokines (CCR4-9) |
question
| How do Regulatory T-cells cells suppress tumor cells? |
answer
| Production of TGFb and IL-10 |
question
| What is the mechanism of recognition by B-lymphocytes? |
answer
| Cell surface tumor antigen, requires T cell help |
question
| How do B-lymphocytes facilitate the killing of targeting cells? |
answer
| ADCC, antibody dependent cell mediated cytotoxicity Compliment activation |
question
| What is the function of TLRs? |
answer
| Can provide additional co-stimulation to T cells TLR-9 is downregulated by the tumor microenvironment and chronic viral infections |
question
| How do tumors employ tolerance? |
answer
| Most tumor cells do not express co-stimulatory receptors needed to activate CTLs Lack of signal 2 induces anergy or death by T cells Most tumor antigens are self or subtly modified (mutated) self proteins, are negatively selected against |
question
| What is the role of CD4+ CD25+ autoreactive T cells? |
answer
| Act to inhibit the activation of other autoreactive T cells, significantly involved in controlling tumors |
question
| How does the loss of Class I MHC help tumors evade the immune system? |
answer
| Loss of Class I MHC is positively selected for by protecting the cell from CTL killing Tumors often lose expression from non-vital genes due to rapid mutations and selection by the immune system |
question
| How does the immune system respond to the loss of MHC Class I on tumor cells? |
answer
| Cytotoxic T-lymphocyte killing falls NK-cell killing rises However, this is not sufficient to control tumor growth, CTLs must be active |
question
| What mediates the loss of tumor antigens by tumor cells? |
answer
| Loss of any protein is positively selected for if it is not essential for growth and is being responded to by the immune system Tumors often lose expression from non-vital genes due to rapid mutations |
question
| What are the properties of an "optimal tumor antigen"? |
answer
| Homogenous expression through the tumor Minimal or no expression on normal tissues High expression levels on tumors Activity in immune repertoire Surface expressed and not shed Plays a role in tumor progression**** |
question
| How do tumor cells modulate their local microenvironment? |
answer
| Some may secrete TGF-Beta or other immunosuppressive factors. Some may express the FasL to kill off tumor specific CTLs |
question
| What are exosomes? |
answer
| Rather than being destroyed within lysosomes, membrane receptors fuse with the plasma membrane and releases exosomes A very common signaling system in the body |
question
| What cells can release exosomes? |
answer
| Mast, T, B, and Dendritic cells Intestinal epithelial cells Macrophages Tumor cells* |
question
| What is the consequence of tumor cells releasing exosomes? |
answer
| Causes systemic effects whereby the immune system becomes more tolerant of the tumors cells or initiating apoptosis by secreting FasL |
question
| How do macrophages participate in chronic inflammation |
answer
| Releases factors that promote angiogenesis and tissue remodeling Also promotes DNA damage (oxygen free radicals) Both of these processes can encourage the growth of tumors or cancer inducing pathogens such as HBV or H. pylori |
question
| What is tumor vaccination? |
answer
| Dendritic cells from patient are removed and “loaded” with tumor antigens, then returned You can also use a plasmid that will express a tumor antigen. Dendritic cells from a patient are transfected with the same plasmid before return |
question
| How can tumor responses be augmented? |
answer
| Tumor cells are removed and forced to express immune modulating genes or costimulatory receptors, then returned |
question
| How are inhibitory pathways blocked in order to combat tumor cells? |
answer
| Normal pathways that are used to inhibit or down-regulate an immune response include CD152/CTLA-4 Antibodies are injected to block this receptor, allowing the immune system to respond to the tumor (self) Essentially initiates auto-immunity |
question
| What is non-specific immune stimulation? |
answer
| Antigen non-specific stimulators of the immune system are injected in the tumor ex. Cytokines, BCG, Anti-CD3 antibodies Causes severe side effects |
question
| What are the different types of passive immunotherapy? |
answer
| Adoptive cell cultures Graft-vs.-Leukemia reaction Anti-tumor antibodies |
question
| What are adoptive cell cultures in passive immunotherapy? |
answer
| Lymphocytes are removed, activated by non-specific tumor antigens, expanded in vitro, then returned to patient Creates Lymphokine-activated killer cells |
question
| What is a Graft-vs.-Leukemia Reaction in passive immunotherapy? |
answer
| Alloreactive T cells are administered along with stem cell transplants Causes death of B cells in the process |
question
| What are anti-tumor antibodies in passive immunotherapy? |
answer
| Antibodies to tumor cell markers are injected to induce humoral immunity |
question
| What is leukapheresis? |
answer
| Blood is removed, partly separated, with the bulk of the blood returning to the patient. The collected blood containing immune cells will be manipulated to increase their cancer-killing ability before being returned to the patient |
