Term
What are the different routes of infection to the CNS |
|
Definition
Blood stream, nerves, direct spread from adjacent focus of infection |
|
|
Term
What is the most common cause of bacterial infection of the nervous system in newborns? |
|
Definition
Group B Strep (S. agalactiae) Also E. coli, Listeria, Klebsiella, and others |
|
|
Term
Which E. coli serotype causes neonatal meningitis? |
|
Definition
|
|
Term
How do newborns most commonly contract bacterial infections of the meningitis? |
|
Definition
At birth due to colonization of th ebirth canal |
|
|
Term
What is the most common cause of bacterial infection of the nervous system in infants and children? |
|
Definition
Strep pneumoniae Neisseria meningitidis Haemophilus influenza |
|
|
Term
What is the most common cause of acute purulent mingitis? |
|
Definition
Strep pneumoniae Neisseria meningitidis Haemophilus influenza |
|
|
Term
Meningitis associated with trauma, neurosurgery, or foreign intracranial bodies is most often caused by what pathogens? |
|
Definition
Staph aureus Staph epidermidis Strep pneumoniae Pseudomonas |
|
|
Term
Intracranial abscesses not associated with trauma or surgery is usually due to what? |
|
Definition
Microaerophilic or anaerobic streptococci, anaerobic Gram-negative bacteria (often mixed aerobic and anaerobic flora of upper respiratory tract origin) |
|
|
Term
What is the rule of thumb when determining whether a pathogen is intracellular or extracellular? |
|
Definition
Intracellular causes granulous lesions Extracellular causes pyogenic and pus formation |
|
|
Term
What is purulent meningitis? |
|
Definition
An infection of the meninges associated with marked acute inflammatory exudates, usually due to bacterial infection |
|
|
Term
What are the symptoms of purulent meningitis? |
|
Definition
Acute onset and rapid progression of fever, stiff neck, irritability, neurologic dysfunction, and PMNs |
|
|
Term
What are the characteristics of chronic meningitis? What causes it? |
|
Definition
Insidious onset, progresses over weeks Most often caused by mycobacteria but can also be due to fungi (granulomatous inflammations) and protozoa (rare) |
|
|
Term
What is asceptic meningitis? |
|
Definition
A syndrome of meningeal inflammation associated with an increase of cells, primarily lymphocytes and mononuclear cells of the CSF Usually due to viral infection |
|
|
Term
What usually precedes asceptic meningitis? |
|
Definition
Viral infections CSF shows an absence of readily cultivable bacteria or fungi |
|
|
Term
|
Definition
CNS dysfunction due to infection: seizures, paralysis, disordered mentation CSF findings may or may not be comparable with asceptic meningitis |
|
|
Term
What causes encephalitis? |
|
Definition
Most often viral infection but can also be due to acute or chronic demyelinating diseases such as postinfectious or allergic encephalomyelitis syndrome |
|
|
Term
|
Definition
Selective destruction of anterior motor horn cells in the spinal cord and/or brainstem |
|
|
Term
What causes poliomyelitis? |
|
Definition
Most commonly due to polio virus Can also be due to Coxsackie virus type A7 or other enteroviruses |
|
|
Term
What is acute polyneuritis? |
|
Definition
An inflammatory disease of the peripheral nerves with characteristic symmetric flaccid paralysis of muscles |
|
|
Term
What causes acute polyneuritis and how is it prevented? |
|
Definition
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 |
|
|
Term
|
Definition
Encephalopathy with fatty infiltration of viscera Seen in childhood, associated with the flu, chicken pox, and the measles |
|
|
Term
What causes Reye's syndrome? |
|
Definition
Cerebral edema, hepatic dysfunction, or hyperammonemia is followed by treatment with aspirin which can precipitate the syndrome |
|
|
Term
How is Reye's syndrome diagnosed? |
|
Definition
Lumbar puncture is first step in a suspected CNS infection, results determine the next step CT and MRI Biopsy of the brain (last resort) |
|
|
Term
What are lumbar punctures contraindicated? |
|
Definition
When intracranial pressure is severely increased |
|
|
Term
What PMN levels would you expect to find in the CSF during a CNS infection? |
|
Definition
Much higher PMNs in bacterial, lower in viral Normal is 0 Viral <50 Pyogenic bacterial >60 Tuberculosis and mycosis <50 |
|
|
Term
What glucose levels would you expect to find in the CSF during a CNS infection? |
|
Definition
Unchanged if viral, lowered if bacterial or fungal |
|
|
Term
What protein levels would you expect to find in the CSF during a CNS infection? |
|
Definition
Slightly increased if viral (30-80), much higher if bacterial or fungal (>60) |
|
|
Term
How is bacterial meningitis confirmed? |
|
Definition
Culture - isolation from CSF or blood Latex agglutination test for Crypto, Strep pneumo, Neisseria, and H. influenza Gram stain |
|
|
Term
What are the clinical findings/symptoms in bacterial meningitis? |
|
Definition
Acute onset of fever and headache Either neck stiffness or altered consciousness or both |
|
|
Term
What types of meningitis cannot be differentiated on clinical grounds alone? |
|
Definition
Hib, meningococcal meningitis and pneumococcal meningitis |
|
|
Term
What lab findings increase the probability of a patient having bacterial meningitis? |
|
Definition
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) |
|
|
Term
How is meningitis treated |
|
Definition
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) |
|
|
Term
What are the general characteristics of Neisseria meningitidis? |
|
Definition
Gram neg cocci, appears in pairs Kidney bean appearance Transmitted via inhaled respiratory droplets Humans are only host |
|
|
Term
Neisseria meningitidis can be cultured on what mediums? |
|
Definition
Blood agar and Chocolate agar |
|
|
Term
What are the important serotypes of Neisseria meningitidis? |
|
Definition
A, B, C, W-135, and Y 50% of cases are caused by B which is the serotype absent in the vaccine |
|
|
Term
Which Neisseria meningitidis serotype is historically associated with epidemic outbreaks? |
|
Definition
|
|
Term
What are the virulence factors of Neisseria meningitidis? |
|
Definition
Meningococcal polysaccharide capsule IgA protease LPS/LOS |
|
|
Term
What inhibits opsonin-mediated phagocytosis in Neisseria meningitidis? |
|
Definition
Meningococcal polysaccharide capsule |
|
|
Term
How does Neisseria meningitidis avoid ciliary activity in order to escape host mucosal defenses? |
|
Definition
|
|
Term
How does Neisseria meningitidis cause endotoxemia? |
|
Definition
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 |
|
|
Term
How does Neisseria meningitidis cause intense subarachnoid inflammation? |
|
Definition
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 |
|
|
Term
How does Neisseria meningitis manifest? |
|
Definition
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) |
|
|
Term
How is Neisseria meningitis diagnosed? |
|
Definition
Culture of CSF, blood, or skin lesions of Neisseria meningitidis on chocolate or blood agar for 12-18hrs |
|
|
Term
What age group is most susceptible to Neisseria meningitidis? |
|
Definition
Children between 6-24mo due to the disappearance of the maternal antibody |
|
|
Term
How is Neisseria meningitis prevented? |
|
Definition
Vaccine against serogroup A, C, and W135 are available Not long lasting, not effective under 2yo Prophylaxis with rifampin for exposed individuals |
|
|
Term
How is Neiserria meningitis treated? |
|
Definition
Penicillin due to good CSF penetration If resistant, use 3rd gen cephalosporin |
|
|
Term
What are the general characteristics of Streptococcus agalactiae (aka group B strep)? |
|
Definition
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) |
|
|
Term
How does Strep agalactiae infect newborns? |
|
Definition
Gains access tot he amniotic fluid or colonizes newborns passing the brith canal |
|
|
Term
What serotypes of Strep agalacitae are most commonly associated with neonatal disease? |
|
Definition
Ia III (only unique one from adults) V |
|
|
Term
What serotypes of Strep agalacitae are most commonly associated with adult disease? |
|
Definition
|
|
Term
What is the primary virulence factor of Strep agalactiae? |
|
Definition
GB capsule, prevents opsono-phagocytosis |
|
|
Term
What defines early onset Strep agalactiae infections? |
|
Definition
Disease in infants younger than 7 days |
|
|
Term
What defines late onset Strep agalactiae infections? |
|
Definition
Disease appearing between 1 week and 3 months of age |
|
|
Term
When are meningitis and focal infections in the bones and joints in cases of GBS infections in infants more likely? |
|
Definition
When they are late onset (between 1 week and 3 months of age) |
|
|
Term
When are high fever, headache and neck stiffness in cases of GBS infections in infants more likely? |
|
Definition
When they are older than 2yo |
|
|
Term
How does a GBS infection in adults generally present? |
|
Definition
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 |
|
|
Term
|
Definition
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) |
|
|
Term
How does GBS present on a CAMP test? |
|
Definition
Produces a characteristic arrowhead area of hemolysis at the junction of S. aureus and S. agalectiae streaks on blood agar |
|
|
Term
How are GBS infections treated? |
|
Definition
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 |
|
|
Term
How is neonatal GBS infection prevented? |
|
Definition
Screen birth canal for colonization in 3rd trimester Assign risk on clinical grounds (eg, prematurity, prolonged membrane rupture, fever) |
|
|
Term
What is the only gram positive diplococcus? |
|
Definition
|
|
Term
What is the distinguishing structural feature of Strep pneumoniae? |
|
Definition
|
|
Term
How is Strep pneumoniae cultured? |
|
Definition
On blood agar, produces round, glistening colonies surrounded by a zone of a-hemolysis |
|
|
Term
Why do S. pneumoniae colonies have a tendency to undergo autolysis? |
|
Definition
Due to their susceptibility to peroxides produced during growth and the action of autolysins, a family of pneumococcal enzymes that degrade peptidoglycan |
|
|
Term
Autolysis of S. pneumoniae is accelerated with what? |
|
Definition
|
|
Term
How is S. pneumoniae differentiated from from S. viridans (another a-hemolytic streptococcus)? |
|
Definition
Optochin sensitivity or by bile solubility tests |
|
|
Term
How is S. pneumoniae infection prevented? |
|
Definition
Vaccine recommended for elderly due to their susceptibility Conjugate vaccine is available to children (not as comprehensive) |
|
|
Term
How are S. pneumoniae infections treated? |
|
Definition
Penicillin and its derivatives Macrolides (penicillin resistant strains) Sulphamethoxazole-trimethoprim (in macrolide resistant strains) Ketolides (when resistant to all other antibiotics) |
|
|
Term
How does S. pneumoniae avoid immunity? |
|
Definition
|
|
Term
What are the characteristics of Listeria monocytogen? |
|
Definition
Gram-positive bacterium; morphology ranges from coccobacilli to long filaments in palisades formation Produces catalase, flagella gives tumbling motility |
|
|
Term
What is unique about Listeria monocytogen growth? |
|
Definition
Can grow at 4 C, unique to non-spore forming bacteria |
|
|
Term
Why is Listeria monocytogen a concern for pregnant women? |
|
Definition
Can cross the placenta, produces widespread abscess in tissues of the fetus Avoid deli meats and cheese |
|
|
Term
How is Listeria monocytogen most commonly contracted? |
|
Definition
Ingestion of contaminated dairy products, poultry and meat (cold growth enhances infectivity) |
|
|
Term
What are the virulence factors of Listeria monocytogen? |
|
Definition
Internalin Listerolysin O (LLO) |
|
|
Term
Listeria monocytogen has what kind of characteristic movement? |
|
Definition
"Like a comet through the evening sky” |
|
|
Term
What is the function of internalin secreted by Listeria monocytogen? |
|
Definition
Bacterial surface protein, induce reorganization of host cell cytoskeleton with formation of a vacuole, within which Listeria enters the cell |
|
|
Term
What is the function of Listerolysin (LLO)? |
|
Definition
Aids escape of Listeria to the cytosol |
|
|
Term
How does Listeria gain a tail? |
|
Definition
In the cytosol using cellular actin filaments |
|
|
Term
Listeria has a tropism for what? |
|
Definition
CNS; seeding of bacteria into the brain and its meninges cause encephalitis and/or meningitis |
|
|
Term
How does Listeria monocytogen infection manifest in adults? |
|
Definition
Fever, headache, stiff neck, vomiting, impaired consciousness, convulsions Abd pain, diarrhea, fever, nausea In immunocompetent: fever, malaise, septicemia and meningitis (most common clinical presentation) |
|
|
Term
How does Listeria monocytogen infection manifest in early-onset neonates? |
|
Definition
Granulomatosis infantisepticum in utero transmission; sepsis with high mortality; disseminated granulomas with central necrosis |
|
|
Term
How does Listeria monocytogen infection manifest in late-onset neonates? |
|
Definition
2–3 weeks after birth from fecal exposure; meningitis with septicemia |
|
|
Term
Listeria meningitis is most common among what type of patients? |
|
Definition
Most common cause of meningitis in renal transplant patients and adults with cancer |
|
|
Term
What mediates immunity to Listeria? |
|
Definition
Both CD4+ and CD8+ T cell subsets are required for resolution and long-lived protection |
|
|
Term
How is Listeria meningitis diagnosed? |
|
Definition
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) |
|
|
Term
How are Listeria infections treated? |
|
Definition
Sensitive to penicillin, ampicillin and TSX Fulminant cases are treated with the combination of gentamicin and ampicillin |
|
|
Term
What is the general appearance of Hemophilus influenza? |
|
Definition
Small gram-negative coccobacilli |
|
|
Term
Hemophilus influenza virulence is dependent on what? |
|
Definition
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 |
|
|
Term
Hemophilus influenza grows on what type of media? What does it require for growth? |
|
Definition
Chocolate agar Requires hematin (X factor) and NAD for growth Can create satellite colonies when grown with Staphylococcus which lyses RBCs |
|
|
Term
How does H. influenza tend to manifest differently depending on age? |
|
Definition
Children under 2 years of age suffer mostly from meningitis Children of 2-5 years of age suffer from epiglottitis and pneumonia |
|
|
Term
How is H. influenza diagnosed? |
|
Definition
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 |
|
|
Term
How is H. influenza infection prevented? |
|
Definition
Conjugated vaccine exists, very effective |
|
|
Term
How are H. influenza infections treated? |
|
Definition
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 |
|
|
Term
How is H. influenza immunity mediated? |
|
Definition
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 |
|
|
Term
What causes Hansen's disease (Leprosy)? |
|
Definition
|
|
Term
What are the physical characteristics of Mycobacterium leprae? |
|
Definition
Identical to M. tuberosis in morphology, structure, and staining Aerobic, acid-fast, rod stains in beads |
|
|
Term
How is Mycobacterium leprae cultured? |
|
Definition
Does not grow in culture but in living cells Very slow growth (12-14day generations) |
|
|
Term
Mycobacterium leprae grows within what type of cells? |
|
Definition
Within macrophages and Schwann cells Humans are the only reservoir |
|
|
Term
What are the virulent factors of mycobacterium leprae? |
|
Definition
Mycoside Phenolic Glycolipid (PGL-1) Lipoarabinomannan (LAM) |
|
|
Term
What are the manifestations of tuberculoid leprosy? |
|
Definition
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 |
|
|
Term
Biopsies of peripheral nerves infected with tuberculoid leprosy usually show what? |
|
Definition
Non-caseating epithelioid granuloma with lymphocytic reactions |
|
|
Term
What causes lepromatous leprosy? |
|
Definition
Uncontrolled Mycobacterium leprae growth due to a lack of or suppressed CMI and DTH Histology/biopsy shows bacteria and lymphoyctes with little macrophage activation |
|
|
Term
What are the manifestations of lepromatous leprosy? |
|
Definition
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 |
|
|
Term
How is lepromin used to distinguish tuberculoid and elpromatous leprosy? |
|
Definition
Is analogous to tuberculin Tuberculoid: positive lepromin test - minimal disease Lepromatous: negative lepromin test – progressive and severe form of disease |
|
|
Term
Tuberculoid leprosy induces what type of immune response? |
|
Definition
TH1-biased response - causes activation of infected macrophages and control of bacterial growth. Patients usually survive though may suffer from chronic disease |
|
|
Term
Lepromatous leprosy induces what type of immune response? |
|
Definition
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 |
|
|
Term
TH1 activates what cytokines? |
|
Definition
IL-1 IFN-gamma TNF-beta TH1 response occurs in tuberculoid leprosy |
|
|
Term
TH2 activates what cytokines? |
|
Definition
IL-4 IL-5 IL-10 TH2 response occurs in lepromatous leprosy |
|
|
Term
How is tuberculoid leprosy treated? |
|
Definition
Sulfones block PABA metabolism, combine with rifampin for 6mo(?) |
|
|
Term
How is lepromatous leprosy treated? |
|
Definition
Sulfones, rifampin, and clofazimine for at least 2yrs |
|
|
Term
Tuberculous meningitis is most common among what demographics? |
|
Definition
Children and HIV patients |
|
|
Term
How does tuberculous meningitis present? |
|
Definition
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 |
|
|
Term
What is the general appearance of Mycobacterium tuberculosis? |
|
Definition
Slender acid-fast, rod shaped bacterium, no spore |
|
|
Term
What is unique about the cell wall of Mycobacterium tuberculosis? |
|
Definition
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 |
|
|
Term
What are the virulent factors for Mycobacterium tuberculosis? |
|
Definition
Mycolic acid Mycosides Sulfolipids Lipoarabinomannan (LAM) – analogous to LPS in gram neg bacteria |
|
|
Term
How is Mycobacterium tuberculosis diagnosed? |
|
Definition
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 |
|
|
Term
|
Definition
An uncommon manifestation of tuberculosis One or more space-occupying CNS lesions, usually causes seizures & focal signs Biopsy is necessary for diagnosis |
|
|
Term
How does tuberculosis meningitis present? |
|
Definition
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 |
|
|
Term
How is tuberculosis meningitis diagnosed? |
|
Definition
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% |
|
|
Term
How do you evaluate a PDD skin test? |
|
Definition
>5mm in HIV+ or anyone with recent TB exposure >10mm in high risk population, IV drug abusers, etc. >15mm in low risk populations |
|
|
Term
What is first line in the treatment of tuberculosis? |
|
Definition
Isoniazid (INH) Ethambutol Rifampin Treated with adjunctive glucocorticoids (such as dexamethasone) for faster resolution of CSF abnormalities and elevated CSF pressure Pyrazinamide Streptomycin |
|
|
Term
How is tuberculosis meningitis treated? |
|
Definition
INH, rifampin, ethambutol and pyrazinamide - 2 mo (bactericidal phase) INH and rifampin – 4 mo (sterilization phase) |
|
|
Term
What is the primary concern when treated tuberculosis? |
|
Definition
Compliance Irregular intake gives rise to resistant strains of TB bacillus |
|
|
Term
What is the general physical appearance of Nocardia? |
|
Definition
Strict aerobic Gram-positive rods that form branched hyphae in tissue and culture |
|
|
Term
Which species of Nocardia are the most commonly involved in human infections? |
|
Definition
N. asteroides and N. brasiliensis |
|
|
Term
N. asteroides and N. brasiliensis grow on what culture medium? |
|
Definition
On blood and chocolate agar with white or orange dry, wrinkled colonies Branching pattern of hyphae growth is indicative |
|
|
Term
N. asteroides and N. brasiliensis tend to have what differing patterns of infection? |
|
Definition
Majority of Nocardia pulmonary and brain infections are due to N. asteroides N. brasiliensis is involved with the cutaneous form |
|
|
Term
How does Nocardia avoid death by phagocytosis? |
|
Definition
Most likely by disrupting acidification of phagosomes or by resisting the oxidative burst |
|
|
Term
How do Nocardia infections present clinically? |
|
Definition
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 |
|
|
Term
How is Nocardia infection treated? |
|
Definition
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 |
|
|
Term
|
Definition
Clostridium botulinum - a gram pos spore forming anaerobe Endospores are highly resistant to heat, can be killed by autoclaving |
|
|
Term
Which strains of Clostridium botulinum are responsible for human botulism? |
|
Definition
|
|
Term
Botulism is associated with what practice? |
|
Definition
|
|
Term
What type of toxin is secreted by Clostridium botulinum? |
|
Definition
Heat labile C. botulinum exotoxin (neurotoxin + AB toxin) are absorbed into the blood from the intestine |
|
|
Term
What is the MoA of botulinum toxin? |
|
Definition
Prevents the attachment of neurotransmitter vesicle to the cytoplasmic membrane of the nerve cells |
|
|
Term
What are the different types of botulism? |
|
Definition
Intestinal - due to ingestion Wound - dirty wounds or dead tissue can be colonized. Bacteria does not invade tissues but toxins diffuse into the blood |
|
|
Term
|
Definition
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 |
|
|
Term
What are the symptoms of viral meningitis? |
|
Definition
Fever, headache, nuchal rigidity Photophobia Myalgias Vomiting Rash |
|
|
Term
What are the symptoms of bacterial meningitis? |
|
Definition
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 |
|
|
Term
What does a Meningoencephalitis panel screen for? |
|
Definition
Herpes Simplex Virus 1/2 Lymphocytic Choriomeningitis Virus California Serogroup Viruses West Nile Virus Eastern and Western Equine Encephalitis Virus St. Louis Encephalitis Virus |
|
|
Term
What are the the expected CSF findings in a viral meningitis infection? |
|
Definition
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 |
|
|
Term
What type of cells are most dominantly present in cases of viral meningitis? |
|
Definition
Lymphocytes (neutrophils may predominate early) |
|
|
Term
What are the the expected CSF findings in a bacterial meningitis infection? |
|
Definition
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) |
|
|
Term
What type of cells are most dominantly present in cases of bacterial meningitis? |
|
Definition
High WBCs, predominately Neutrophils |
|
|
Term
What is the most common cause of viral meningitis? |
|
Definition
Enterovirus (includes Coxsackievirus, echovirus, etc) |
|
|
Term
What are the California serogroup viruses? |
|
Definition
Belongs to the Bunyaviridae family La Crosse virus California encephalitis virus Jamestown canyon virus Snowshoe hare virus |
|
|
Term
What is distinct about the detection of California serogroup viruses? |
|
Definition
Not recoverable in CSF during acute phase |
|
|
Term
What are the characteristics of encephalitis due to a measles (Paramyxoviridae family) infection? |
|
Definition
Insidious onset of personality change Poor school performance Progressive intellectual deterioration Development of myoclonic jerks (periodic muscle spasms) Motor dysfunctions |
|
|
Term
What are the unique characteristics of chronic encephalitis due the measles? |
|
Definition
Subacute sclerosing panencephalitis (SSPE) Occurs about 7 years after infection with measles, mainly in those infected before 2yo |
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|
Term
Meningitis most commonly occurs in mumps infections (Paramyxoviridae family) when what other symptoms are present? |
|
Definition
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 |
|
|
Term
What are the characteristics of meningitis due to Lymphocytic choriomeningitis virus (LCMV)? |
|
Definition
Uncommon infection Lasts 1-3 weeks, but 15% have biphasic symptoms with meningeal signs and more prominent headache in second phase |
|
|
Term
How does meningitis due to HIV infection usually present? |
|
Definition
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 |
|
|
Term
How is viral encephalitis best detected? |
|
Definition
MRI (shows better than meningitis infections) |
|
|
Term
What is the most common cause of viral encephalitis? |
|
Definition
|
|
Term
What are the symptoms of HSV induced viral encephalitis? |
|
Definition
Altered consciousness >fever >headache >disorientation >behavior or personality changes >seizures |
|
|
Term
What distinguishes the strains of HSV that cause viral encephalitis? |
|
Definition
HSV-1 more likely in sporadic encephalitis HSV-2 more common in recurrent benign lymphocytic meningitis |
|
|
Term
What are the unique characteristics of viral encephalitis caused by West Nile Virus? |
|
Definition
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 |
|
|
Term
St. Louis encephalitis virus is most likely to cause encephalitis among what demographic? |
|
Definition
Predominant in those over 60yo In younger, meningitis is almost just as common |
|
|
Term
What is a common complication of St. Louis encephalitis virus? |
|
Definition
Seizures occur in 47% of patients |
|
|
Term
What are the characteristics of encephalitis caused by Eastern/Western encephalitis virus |
|
Definition
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 |
|
|
Term
How does Rabies virus infect humans? |
|
Definition
Animal bites introduce virions in saliva which invade motor & sensory nerves |
|
|
Term
How long does Rabies virus lay dormant? |
|
Definition
Can incubate anywhere from 7 days to greater than 6 years (median is 1-2 months) |
|
|
Term
What are the characteristics of "furious" rabies? |
|
Definition
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 |
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|
Term
What are the characteristics of "dumb" rabies? |
|
Definition
20% of cases Paresthesias, weakness, and flaccid paralysis in the bitten limb |
|
|
Term
What is abortive poliomyelitis? |
|
Definition
Nonspecific febrile illness caused by poliovirus for 2-3 days without CNS involvement |
|
|
Term
What are the symptoms of asceptic meningitis due to poliovirus (nonparalytic poliomyelitis)? |
|
Definition
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 |
|
|
Term
How does paralytic poliomyelitis progress (usually less than 2% of the infections)? |
|
Definition
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 |
|
|
Term
What are the basic problems with transplantation therapy? |
|
Definition
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 |
|
|
Term
What are the hallmark of successful transplantation? |
|
Definition
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 |
|
|
Term
|
Definition
A graft from one part of the body to another location on the same individual |
|
|
Term
|
Definition
A graft between genetically identical individuals (identical twins) |
|
|
Term
|
Definition
A graft from a genetically dissimilar donor to a recipient of the same species |
|
|
Term
|
Definition
A graft from a donor of another species |
|
|
Term
|
Definition
Refers to the immune reactions provoked by the alloantigen |
|
|
Term
|
Definition
Refers to an antigen that differs between members of the same species (e.g. HLA molecules and blood group antigens) |
|
|
Term
What are minor histocompatibility antigens? |
|
Definition
Allelic forms of normal cellular proteins that happen to be different between donor and recipients; these non-MHC antigens can also induce graft rejection |
|
|
Term
What is most commonly responsible for allograft rejection? |
|
Definition
HLA (MHC) mismatching is generally most important However, multiple minor histocompatibility mismatching can be as severe as HLA mismatching |
|
|
Term
Which MHC mismatching causes the most severe rejection in transplants? |
|
Definition
Mismatching of MHC II (HLA-DQ, DP, DR) often causes more rapid and severe rejection than mismatching MHCI (HLA-A, B, C) |
|
|
Term
Which major HLA are considered for matching? |
|
Definition
|
|
Term
Which blood group only has the core structure and therefore are considered universal donors? |
|
Definition
|
|
Term
Which blood group has both antigens and therefore can only be given the same blood group or the O blood group? |
|
Definition
|
|
Term
How are gut bacteria involved in the production of blood group antibodies? |
|
Definition
Gut bacteria bear antigens that are similar or identical to the blood group antigens which stimulates the production of Ab against these Ag |
|
|
Term
What is a cross-matching test? |
|
Definition
Refers to a method of direct assessment of reactivity between recipients serum and donors blood cells |
|
|
Term
How is tissue typing done via serology? |
|
Definition
Microcytotoxicity test or lymphocyte cross-matching: patient’s serum is cross-matched with potential donors lymphocytes Tests all HLA loci |
|
|
Term
How is tissue typing done via DNA or molecular techniques? |
|
Definition
Via PCR Tests all HLA loci |
|
|
Term
How is tissue typing done via mixed lymphocyte reaction/response? |
|
Definition
Done with in vitro culture containing blood leukocytes from both donor and recipient For DR (DQ, DP) molecules |
|
|
Term
Hyperacute rejection of transplantation is comparable to what type of hypersensitivity? |
|
Definition
Type III Immune complex deposition cause complement activation in blood vessel wall |
|
|
Term
What can causes hyperacute rejection of transplantation? |
|
Definition
Preexisting antibodies against A, B, O or HLA antigens in the recipient’s serum |
|
|
Term
How might someone gain pre-formed anti-HLA Abs? |
|
Definition
Generation from pregnancy, blood transfusions, or previous tranplantation |
|
|
Term
Acute rejection of transplantation is comparable to what type of hypersensitivity? |
|
Definition
Type IV hypersensitivity Mediates acute rejection via generation of alloreactive effector cells dependent on whether they are presented by MHCI or MHCII |
|
|
Term
|
Definition
Recognition of the alloantigen by the recipient’s T cells in a direct or indirect fashion. Seen in acute rejection of transplantation |
|
|
Term
What is direct allorecognition? |
|
Definition
HLA Ags presented on the donor APC interacts w/ CD4 and CD8 T cells |
|
|
Term
What is indirect allorecognition? |
|
Definition
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 |
|
|
Term
How do CD4 alloreactive cells cause transplant rejection? |
|
Definition
They migrate in blood to the graft and activate macrophages to exacerbate the inflammation |
|
|
Term
How do CD8 alloreactive cells cause transplant rejection? |
|
Definition
They migrate in blood to the graft and attack the cells in the transplanted tissue directly |
|
|
Term
How is acute rejection development significant when it comes to treatment? |
|
Definition
Develops over a period of days and therefore, unlike hyperacute rejection can be reduced or even prevented |
|
|
Term
What causes chronic rejection of transplantation? |
|
Definition
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 |
|
|
Term
How does chronic rejection of transplantation manifest? |
|
Definition
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 |
|
|
Term
What corticosteroid is most commonly used for transplant patients? |
|
Definition
Prednisone Needs to be converted to prednisolone to be active Must be combined with others to prevent graft rejection |
|
|
Term
What is the MoA of prednisone? |
|
Definition
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 |
|
|
Term
What are the effects of prednisone? |
|
Definition
Inhibits inflammatory mediators Inhibits inflammatory cell migration Promotes apoptotic death of leukocytes, including lymphocytes |
|
|
Term
What is the MoA of Azathioprine? |
|
Definition
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 |
|
|
Term
What are the effects of Azathioprine? |
|
Definition
Damages all the tissue of the body normally active in cell division, especially bone marrow, intestinal epithelium, and hair follicles |
|
|
Term
What is the main concern in using Azathioprine as a cytotoxic immunosuppressant? |
|
Definition
|
|
Term
What is the MoA of Cyclophosphamide? |
|
Definition
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 |
|
|
Term
What is Cyclophosphamide used for? |
|
Definition
Both pre- and post-transplant patient therapy Used as an alternative to methotrexate |
|
|
Term
Cyclophosphamide has what significant side effect? |
|
Definition
Very toxic to the urinary bladder |
|
|
Term
What is the drug of choice for inhibiting GVHD in bone marrow transplant patients? |
|
Definition
|
|
Term
What is the MoA of Methotrexate? |
|
Definition
Prevents DNA replication by inhibiting dihydrofolate reductase essential for thymidine synthesis |
|
|
Term
|
Definition
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 |
|
|
Term
|
Definition
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) |
|
|
Term
|
Definition
Isolated from a soil bacterium, inhibits T cell activation by preventing signal transduction from IL-2 receptors |
|
|
Term
What are the antibodies specific for T cells? |
|
Definition
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 |
|
|
Term
Bone marrow transplantation is most commonly prescribed for what? |
|
Definition
|
|
Term
What hematopoietic diseases are treatable with bone marrow transplant? |
|
Definition
SCID, Fanconi's anemia, thalassemia major, sickle-cell anemia |
|
|
Term
How is the preparative phase for bone marrow transplant different from solid organ transplants? |
|
Definition
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 |
|
|
Term
What is the purpose of myeloablative therapy? |
|
Definition
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 |
|
|
Term
What is required for a successful bone marrow transplant? |
|
Definition
The donor and recipient should have at least one HLA class I and one HLA class II allotype in common (more is better) |
|
|
Term
What causes Graft-versus-Host Disease? |
|
Definition
Mature T lymphocytes in donor bone marrow recognize tissues of the new host as foreign and cause a severe inflammatory disease in the recipient |
|
|
Term
What are the symptoms of acute GVHD? |
|
Definition
A rash Diarrhea Pneumonitis Liver damage |
|
|
Term
What is characterized by chronic GVHD? |
|
Definition
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 |
|
|
Term
How does the skin rash seen in bone marrow transplant BMT present? |
|
Definition
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 |
|
|
Term
What is histologically distinct in skin rashes in BMT? |
|
Definition
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 |
|
|
Term
What is characteristics about GI disturbance in GVHD? |
|
Definition
Appears after skin manifestation Causes watery diarrhea |
|
|
Term
How is the liver affected in GVHD? |
|
Definition
Infiltrated with inflammatory cells, causes liver enzymes to rise |
|
|
Term
What are the different grades of skin rashes in GVHD? |
|
Definition
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 |
|
|
Term
What are the different grades of liver damage in GVHD? |
|
Definition
Based on serum bilirubin I: 2-3 mg/dl II: 3-6 mg/dl III: 6-15 mg/dl IV: 15 mg/dl |
|
|
Term
What are the different grades of GI disturbance in GVHD? |
|
Definition
>500 ml diarrhea/day >1000 ml diarrhea/day >1500 ml diarrhea/day Severe abdominal pain with or without ileus |
|
|
Term
Who are the best possible donors for BMT? |
|
Definition
|
|
Term
Why do some HLA identical siblings still develop GVHD? |
|
Definition
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 |
|
|
Term
What are minor histocompatibility antigens? |
|
Definition
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 |
|
|
Term
How can minor histocompatibility antigens precipitate GVHD? |
|
Definition
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 |
|
|
Term
How does GVHD impart a beneficial effect on leukemia patients? |
|
Definition
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 |
|
|
Term
What is the purpose of autologous bone marrow transplants? |
|
Definition
Designed to help patients clinically eligible for BMT unable to find a suitable HLA-matched donor |
|
|
Term
What are autologous bone marrow transplants? |
|
Definition
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 |
|
|
Term
What are the limitations of autologous bone marrow transplants? |
|
Definition
Frequent relapse of cancer compared to allogenic transplant |
|
|
Term
What is a hematopoietic stem cell transplant? |
|
Definition
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 |
|
|
Term
How many cells are required to perform a hematopoietic stem cell transplant? |
|
Definition
0.25 to 0.5 billion cells are required for prompt engraftment after transplantation |
|
|
Term
What are the Transmissable Spongiform Encephalopathies (TSE)? |
|
Definition
Creutzfeld-Jakobs Disease (CJD) Bovine Spongiform Encephalopathy (BSE) Kuru (humans), scrapie (sheep) Chronic wasting disease (CWD) |
|
|
Term
What are normal, healthy prions (PrPc)? |
|
Definition
Product of PRNP gene on chromosome 20 Glycoprotein anchored to cell membrane Well-conserved in most mammalian species Predominantly expressed in neuronal cells |
|
|
Term
What is the function of normal healthy prions (PrPc)? |
|
Definition
Maintenance of neuronal integrity in the brain Possible role in Cu metabolism & cellular response to oxidative stress |
|
|
Term
What are the characteristics of aberrant PrPsc? |
|
Definition
Resistant to proteolysis Insoluble in nondenaturing detergents |
|
|
Term
What how are aberrant prions (PrPsc) formed? |
|
Definition
Conformation change from a predominantly α-helical structure to predominantly β-sheets Endogenous PrPc interacts with PrPsc, converts PrPc to PrPsc, can begin spontaneous generation |
|
|
Term
What are the symptoms of prion disorders (Transmissable Spongiform Encephalopathies)? |
|
Definition
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 |
|
|
Term
|
Definition
Restricted to the highlands of New Guinea Ritualistic cannibalism lead to spreading of spongiform encephalopathies (prion diseases) due to brain tissue being highly infectious |
|
|
Term
What is the most common parasitic infection of the CNS? |
|
Definition
|
|
Term
How is Toxoplasma gondii most commonly contracted? |
|
Definition
Ingestion of tissue cysts in undercooked meat Primary hosts are cats |
|
|
Term
What are the 3 infectious stages of Toxoplasma gondii? |
|
Definition
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) |
|
|
Term
What type of people are more susceptible to Toxoplasma gondii infection? |
|
Definition
Immune response normally neutralizes and removes tachyzoites Immunocompromised at heightened risk, can cause necrotizing encephalitis |
|
|
Term
What are the symptoms of Toxoplasmosis? |
|
Definition
Fever, malaise, night sweats, sore throat Retroperitoneal & mesenteric lymphadenopathy Chorioretinitis CNS disease in 50% of infected immunocompromised patients |
|
|
Term
What are the complications of congenital toxoplasmosis? |
|
Definition
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 |
|
|
Term
What is the deadliest complication of Plasmodium falciparum (malaria)? |
|
Definition
Cerebral malaria The major cause of death from malaria |
|
|
Term
What are the symptoms of cerebral malaria? |
|
Definition
Encephalitic syndrome Ataxia, seizures, hemiplegia, coma, death Parasitized RBCs are sequestered in the cerebrum, cerebellum, and medulla oblongata, causes compensatory vasodilation, increased brain volume |
|
|
Term
Cerebral malaria patients who have undergone successful parasitic treatment can still retain what negative effects? |
|
Definition
Can still retain residual neurological damage Memory, learning, and language impairments Visuospatial and motor deficits Psychiatric disorders |
|
|
Term
Describe the life cycle of Plasmodium falciparum |
|
Definition
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 |
|
|
Term
What causes RBC Rosettes? What are they? |
|
Definition
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 |
|
|
Term
What is Naegleria fowleri? |
|
Definition
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 |
|
|
Term
How does Naegleria fowleri cause primary amebic meningoencephalitis (PAM)? |
|
Definition
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 |
|
|
Term
What are the symptoms of amebic meningoencephalitis (N. fowleri)? |
|
Definition
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 |
|
|
Term
What is the most common cause of death due to amebic meningoencephalitis (N. fowleri)? |
|
Definition
Cardiorespiratory arrest and pulmonary edema |
|
|
Term
Describe the pathophysiology and virulence of Naegleria fowleri |
|
Definition
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 |
|
|
Term
How is Naegleria fowleri diagnosed? |
|
Definition
Spinal tap ASAP shows: Elevated protein Normal or slightly reduced glucose levels WBC high (400-26000/μL) RBC high Wet mount positive for motile trophozoites Smears can be stained using Wright’s/Giemsa stain |
|
|
Term
How is Naegleria fowleri treated? |
|
Definition
Early diagnosis is essential due to rapid course of infection Near immediate chemotherapy is essential for survival |
|
|
Term
What is the characteristic feature of Acanthamoeba? |
|
Definition
The presence of spine-like pseudopods called acathapodia |
|
|
Term
How are Acanthamoeba infections contracted? |
|
Definition
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 |
|
|
Term
What are the consequences of unsuppressed Acanthamoeba infections? |
|
Definition
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 |
|
|
Term
What are the risk factors for granulomatous amebic encephalitis (GAE) due to Acanthamoeba infection? |
|
Definition
Chronically ill, immunologically impaired, Malignancies, SLE, HIV, Hodgkin’s, DM Infections are associated with trauma and underlying disease |
|
|
Term
What is Trypanosoma brucei gambiense? |
|
Definition
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 |
|
|
Term
What is Trypanosoma brucei rhodesiense? |
|
Definition
East African (or Rhodesian) trypanosomiasis Zoonotic disease (animal reservoir) Rapidly progressing disease |
|
|
Term
|
Definition
Potentially infectious mitochondrial DNA (?) |
|
|
Term
Describe the progression of African Sleeping Disease (Trypanosomiasis) |
|
Definition
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 |
|
|
Term
What happens when Trypanosomes (African sleeping disease) crosses the blood brain barrier? |
|
Definition
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 |
|
|
Term
Taenia solium is most commonly contracted through what means? |
|
Definition
Eggs ingested from poorly cooked pork, hatch in the stomach |
|
|
Term
What are the symptoms of neurocystercercosis? |
|
Definition
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 |
|
|
Term
How does Taenia solium avoid the immune system? |
|
Definition
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 |
|
|
Term
What is Echinococcus granulosus? How is it contracted? |
|
Definition
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 |
|
|
Term
How does Echinococcus granulosus progress? |
|
Definition
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 |
|
|
Term
What are the characteristics of hydatid cysts (Echinococcus granulosus)? |
|
Definition
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 |
|
|
Term
How is Echinococcus granulosus treated? |
|
Definition
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 |
|
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Term
What is the most common cause of human eosinophilic meningitis? |
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Definition
Cerebral Angiostrongyliasis (Angiostrongylus cantonensis) |
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Term
How are Angiostrongylus cantonensis infections contracted? |
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Definition
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 |
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Term
What are the symptoms of Cerebral Angiostrongyliasis? |
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Definition
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 |
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Term
How is Cerebral Angiostrongyliasis diagnosed? |
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Definition
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 |
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Term
What is Cryptococcus neoformans? |
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Definition
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 |
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Term
What are the virulence factors of Cryptococcus neoformans? |
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Definition
Polysaccharide capsule Ability to grow at 37 degC Phenol oxidase enzyme prevents formation of toxic hydroxyradicals and oxidative stress |
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Term
What are the symptoms of meningoencephalitis due to Cryptococcus neoformans? |
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Definition
Antigen in the CSF can potentially change the osmolality affecting flow and absorption Increases intracranial press Headaches, vision loss, early death |
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Term
What is Coccidioides immitis infection (coccidiodomycosis) and how is it contracted? |
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Definition
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 |
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Term
What are the symptoms of CNS disseminated Coccidioides immitis (coccidiodomycosis)? |
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Definition
Chronic granulomatous meningitis in the basilar meninges, cerebral and cerebellar abscesses, headache, nausea, vomiting, altered mental status Intense immunologic rashes when disseminated |
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Term
What is the most lethal form of coccidioidomycosis? |
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Definition
Dissemination to the CNS causes chronic granulomatous meningitis (basilar meninges), cerebral and cerebellar abscesses. Causes headache, nausea, vomiting, altered mental status |
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Term
What are Tumor-Specific Transplantation Antigens (TSTA)? |
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Definition
Unique to tumor cells and not expressed on/in normal cells Responsible for rejection of tumor |
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Term
What are Tumor Associated Transplantation Antigens (TATA)? |
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Definition
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 |
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Term
Which tumor antigen is considered a product of mutated genes or oncogenic virus genes? |
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Definition
Tumor-Specific Transplantation Antigens (TSTA) |
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Term
Which tumor antigen is considered to be a product of abnormal expression of normal genes? |
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Definition
Tumor Associated Transplantation Antigens (TATA) |
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Term
Tumor Associated Transplantation Antigens (TATA) are composed of what normally expressed antigens? |
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Definition
Oncofetal antigens Altered glycolipid and glycoprotein antigens Tissue-specific differentiation antigens |
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Term
What is the consequence of gene mutations producing new antigens? |
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Definition
A change in the sequence changes what peptides can be presented. This can also be caused by oncogenic viral infection |
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Term
Papilomavirus has been linked to the development of which associated tumors? |
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Definition
Benign warts Carcinoma of the uterine cervix |
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Term
HBV has been linked to the development of which associated tumors? |
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Definition
Liver cancer/hepatocellular carcinoma |
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Term
EBV has been linked to the development of which associated tumors? |
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Definition
Burkitt's lymphoma Nasopharyngeal carcinoma B-cell lymphoproliferative disease |
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Term
HIV and HHV8 have been linked to the development of which associated tumors? |
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Definition
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Term
What is the consequence of expression of fetal proteins in tumor cells? |
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Definition
Allows the presentation of peptides the majority of the immune system has never seen |
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Term
How many MHC:peptide complexes are required on a target cell to activate a T cell? |
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Definition
10-100 identically loaded MHC;Peptide complexes Without a costimulatory receptor (CD4 or CD8), it would take 10,000 |
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Term
What are tissue-specific differentiation antigens? |
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Definition
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) |
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Term
What are the abnormal cell surface antigens continually secreted by most human tumors? |
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Definition
Gangliosides (GM2, GD2, GD3) Blood group antigens Mucins |
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Term
What abnormal markers are recognized by NK cells? |
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Definition
Altered cell-surface glycoproteins Loss of class I MHC Bound antibodies |
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Term
How do NK cells facilitate killing targeted cells? |
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Definition
Release of cytotoxic granules |
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Term
Activation and killing by NK cells is dependent on what factor? |
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Definition
The extent of inhibitory and activating receptors being used. If there are more activating than inhibitory, the NK cell will be activated |
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Term
What are the different protein families of NK cell receptors? |
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Definition
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 |
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Term
What abnormal markers are recognized by macrophages? |
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Definition
Bound antibodies Receptor interactions such as NKG2D receptor expression |
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Term
How do macrophages facilitate the killing of targeted cells? |
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Definition
Phagocytosis Production of NO |
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Term
How do actively replicating tumor cells continue to mutate while growing in number? |
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Definition
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 |
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Term
What is recognized by CD8+ T cells? |
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Definition
Tumor antigens presented in class I MHC |
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Term
How do CD8+ T cells facilitate the killing of targeted cells? |
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Definition
Release of cytotoxic granules Fas receptor ligation |
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Term
What is the mechanism of recruitment by Regulatory T-cells (Treg)? |
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Definition
Tumor expressed chemokines (CCR4-9) |
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Term
How do Regulatory T-cells cells suppress tumor cells? |
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Definition
Production of TGFb and IL-10 |
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Term
What is the mechanism of recognition by B-lymphocytes? |
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Definition
Cell surface tumor antigen, requires T cell help |
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Term
How do B-lymphocytes facilitate the killing of targeting cells? |
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Definition
ADCC, antibody dependent cell mediated cytotoxicity Compliment activation |
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Term
What is the function of TLRs? |
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Definition
Can provide additional co-stimulation to T cells TLR-9 is downregulated by the tumor microenvironment and chronic viral infections |
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Term
How do tumors employ tolerance? |
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Definition
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 |
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Term
What is the role of CD4+ CD25+ autoreactive T cells? |
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Definition
Act to inhibit the activation of other autoreactive T cells, significantly involved in controlling tumors |
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Term
How does the loss of Class I MHC help tumors evade the immune system? |
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Definition
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 |
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Term
How does the immune system respond to the loss of MHC Class I on tumor cells? |
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Definition
Cytotoxic T-lymphocyte killing falls NK-cell killing rises However, this is not sufficient to control tumor growth, CTLs must be active |
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Term
What mediates the loss of tumor antigens by tumor cells? |
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Definition
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 |
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Term
What are the properties of an "optimal tumor antigen"? |
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Definition
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**** |
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Term
How do tumor cells modulate their local microenvironment? |
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Definition
Some may secrete TGF-Beta or other immunosuppressive factors. Some may express the FasL to kill off tumor specific CTLs |
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Term
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Definition
Rather than being destroyed within lysosomes, membrane receptors fuse with the plasma membrane and releases exosomes A very common signaling system in the body |
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Term
What cells can release exosomes? |
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Definition
Mast, T, B, and Dendritic cells Intestinal epithelial cells Macrophages Tumor cells* |
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Term
What is the consequence of tumor cells releasing exosomes? |
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Definition
Causes systemic effects whereby the immune system becomes more tolerant of the tumors cells or initiating apoptosis by secreting FasL |
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Term
How do macrophages participate in chronic inflammation |
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Definition
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 |
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Term
What is tumor vaccination? |
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Definition
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 |
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Term
How can tumor responses be augmented? |
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Definition
Tumor cells are removed and forced to express immune modulating genes or costimulatory receptors, then returned |
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Term
How are inhibitory pathways blocked in order to combat tumor cells? |
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Definition
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 |
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Term
What is non-specific immune stimulation? |
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Definition
Antigen non-specific stimulators of the immune system are injected in the tumor ex. Cytokines, BCG, Anti-CD3 antibodies Causes severe side effects |
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Term
What are the different types of passive immunotherapy? |
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Definition
Adoptive cell cultures Graft-vs.-Leukemia reaction Anti-tumor antibodies |
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Term
What are adoptive cell cultures in passive immunotherapy? |
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Definition
Lymphocytes are removed, activated by non-specific tumor antigens, expanded in vitro, then returned to patient Creates Lymphokine-activated killer cells |
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Term
What is a Graft-vs.-Leukemia Reaction in passive immunotherapy? |
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Definition
Alloreactive T cells are administered along with stem cell transplants Causes death of B cells in the process |
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Term
What are anti-tumor antibodies in passive immunotherapy? |
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Definition
Antibodies to tumor cell markers are injected to induce humoral immunity |
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Term
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Definition
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 |
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