MBIO 4823 final pt 2

in mouse models, what is the natural resistance-associated macrophage protein? (TB)

Bcg

Bcg is the genetic locus involved in... (TB)

susceptibility of different strains of mice to TB; mice with this are more resistant to TB

true or false: Bcg is found in humans (TB)

false; none found in humans to date, but remains a very active research field

active research field of TB includes...

•Identifying susceptible members of the population

•Candidates for gene therapy

true or false: intracellular pathogens don't always have it their way (TB)

true

immune system (MHC I) interaction with cytotoxic lymphocyte cells such as... (TB)

CTLs or Tc (T cells)

what is the major histocompatibility complex (TB)?

MHC I antigen pathway

true or false: all cells have MHC complexes so the host can recognize its own cells (TB)

true; self recognition

protein antigens (bacterial, viral, etc) degraded by what in the cytoplasm are transported across the endoplasmic reticulum membrane? (TB)

the phagosome

what forms the endoplasmic reticulum membrane?

TAP aka transporters associated with antigen processing

MHC-I protein is held in place by a what until the peptide is bound? (TB)

chaperone

chaperone is released and the protein complex is transported to the cell surface and interacts with what? (TB)

T-cell receptors (TCRs)

what are intracellular pathogens? (TB)

antigens processed from an internal source-cytoplasm

what do perforin and granzymes do? (TB)

make holes in cell membrane PMF collapses which initiates apoptosis killing infected host cell along with internal bacteria

perforin and granzymes example (TB)

granulysin

TB is highly contagious so isolation in what pressure hepa-filtered room is a source of control?

negative pressure

true or false: face masks with high efficiency filters are used for TB control

true

true or false: early diagnosis of TB is difficult, symptomatic patients, slow gradual progression and symptoms may be slow to show themselves

true

cough with thick, cloudy, and sometimes bloody mucus from what for more than 2 weeks becomes a cause for concern? (TB)

the lungs (sputum)

test for the the presence of what in sputum must be present in large numbers to perform tuberculin test?

"acid-fast" bacillus

what protein is extracted from M. tuberculosis is injected into individual and a localized immune reaction is seen? (TB)

tuberculin

pre-primed TH CD4 cells at the site of injection secrete what? (TB)

cytokines

leucocytes and macrophages are recruited to the injection site leading to... (TB)

the immune reaction

a positive tuberculin test shows...

redness and swelling within 48-72 hours

what does tuberculin test demonstrate?

demonstrates prior exposure to the bacterium

what is a problem with the tuberculin test?

takes 4 wks after exposure, so recent infections are missed

how many tuberculin tests are performed?

2 tests, 4 weeks part are performed

past exposure related Mycobacterium bovis found in soil or vaccination by BCG leads to...

false positives / cross-reactivity

a search for better TB tests to bypass the need to...

culture this slow growing organism

PCR and sequencing is extremely... (TB)

rapid

16S rRNA genes but low copy number therefore... (TB)

other targets favored

probes to what elements (in other regions of the chromosome) that are specific to M. tuberculosis strains?

insertion elements

What is the IGRA test? (TB)

Interferon Gamma Release Assay; blood tests for TB infection

white blood cells from persons infected with M. tuberculosis will release what when mixed with antigens (substances that can produce an immune response) derived from M. tuberculosis?

interferon-gamma (IFN-g)

true or false: prior BCG (bacille Calmette-Guérin) vaccination does cause a false-positive IGRA test result

false; does not cause a false-positive IGRA test result

what test is a new molecular test that can diagnose TB in one hour?

Truenat TB test; there are now several different assays which have expanded the capability of the test

Truenat TB tests for resistance to what drug?

rifampicin

Truenat TB test utilizes real-time PCR from...

DNA extracted from sputum

Truenat TB test target is what?

an insertion sequence IS1081

what inhibits protein synthesis? (TB)

Streptomycin; many pathogens became resistant and therefore no longer made in US so now imported from less developed countries

true or false: with no selective pressure many pathogens have lost resistance

true

true or false: most antibiotics are ineffective to TB

true; penicillins, tetracyclines, cephalosporins

special antibiotics for TB treatment is used including...

isoniazid, rifampin, and pyrazinamide

isoniazid is used for 9 months and inhibits... (TB)

mycolic acid synthesis aka the waxy cell-wall

isoniazid inhibits waxy cell-wall so M. tuberculosis is susceptible to...

macrophages and the phagolysosome process of killing bacterium by the oxidative burst and enzymes

rifampin inhibits... (TB)

processing of RNA and shuts down protein synthesis

pyrazinamide disrupts... (TB)

synthesis of fatty acids in cell walls

both rifampin and pyrazinamide need to be taken in...

the first 2 months along with other drugs

to combat M. tuberculosis resistance a combination of drugs are used...

Isoniazid-rifampin; most effective combination 90%

M. tuberculosis resistance occurs at high frequency with what percentage of mortality?

50%

if antibiotics so effective (ideal conditions), why resistance so high? (TB)

because slow growing and long treatment times (9-12 months) so patients don't finish the drug program 10% of the time (early programs had officials to ensure compliance)

MDR-TB aka multiple drug resistant TB is resistant to how many anti-TB drugs?

2 or more (isoniazid and rifampin)

1990s what strain emerged in New York? (TB)

W strain; resistant to almost all of the antibiotics used and highly virulent and infectious

the W strain could have gone out of control so drastic measures became intact such as...

\-isolation

\-surgical removal of lung tissue

\-use of experimental drugs

the W strain had what percent of mortality? (TB)

74%

XDR-TB aka Extremely Drug Resistant TB is resistant to...

isonizid and rifampin and at least 3 second line drugs

true or false: XDR-TB strains are a major problem and are predicted to kill millions

true

true or false: TDR-TB aka Totally Drug Resistant TB is an old strain

false; new deadly strain discovered in India

what strain is used as BCG (Bacillus Calmette-Guérin) vaccine? (TB)

avirulent M. bovis strain; French scientists transferred for 231 generations over 13 yrs to weaken this "attenuated" diseased producing species

BCG vaccine allows macrophages to enter and breaks down eliciting... (TB)

an immune response

true or false: BCG vaccine is easily administered

true; administered orally and can be given to infants

an attenuated vaccine is a vaccine created by... (TB)

reducing the virulence of a pathogen, but still keeping it viable (or "live"); ex: BCG vaccine

attenuation takes and infectious agent and alters it so that it becomes... (TB)

harmless or less virulent

when first used, the BCG vaccine was stored in... (TB)

the same refrigerator as live strains; become contaminated and killed many babies so took many years for trust in this to be restored

the BCG vaccination does not prevent... (TB)

reactivation

BCG protective range 0 to 80% so extremely variable between populations with... (TB)

genetic predisposition of human populations; makes all patients skin tests positive

recent discovery of what that convert avirulent vaccine strains to potential deadly pathogen? (TB)

bacteriophages

why introduce other M. tuberculosis genes into BCG vaccine?

for effective antigens from several bacterial species for a multipurpose vaccine effective against several diseases

the use of psoralen and UV treatment cross-links DNA and prevents...

DNA synthesis while allowing protein synthesis and metabolism

advantage of preventing DNA synthesis while allowing protein synthesis and metabolism

organisms do not multiply but remain alive and produce antigens that the immune system recognizes and mounts a response

several new vaccines are being developed but clinical trials... (TB)

take a long time due to the nature of the disease

in the search for other vaccine targets, different antigens expressed during these phases of growth include... (TB)

alpha-crystallin

what are Resuscitation-promoting factors (rpf genes)? (TB)

essential for reactivation of growth from the dormant or latent phase

true or false: knocking out rpf genes to prevent reactivation of TB is an active area of research

true

In the United States, up to 13 million people may have...

latent TB infection

what is Direct Observational Therapy Short aka DOTS course?

adopted by WHO in 1992 to combat noncompliance and complacency; health care workers physically watch patients swallow their daily dose of anti-TB drugs (back to the old days)

within first 2-4 weeks of DOTS, patients become...

noninfectious; very effective (Bangladesh 85% cure rate, Peru 90% cure rate)

what is the third tuberculosis drug to receive FDA approval in more than 40 years?

pretomanid

pretomanid has activity against what?

static M. tuberculosis isolates that survive under anaerobic conditions

pretomanid has bactericidal activity comparable to that of the existing drug...

metronidazole

TB has killed millions in the past and is the leading cause of death from...

a curable infectious disease (30 million deaths over the next decade)

TB is on the rise with 1 person infected every second in...

resource-poor countries and those blighted with HIV

true or false: TB is largely forgotten in the USA

true

almost 125 years after the discovery of the cause of TB, it is still called...

"The Peoples Plague" and a scourge of mankind

Chlamydia trachomatis is known as...

the silent destroyer

Chlamydia trachomatis affects what system?

urogenital system

although the general public are familiar with Syphilis and Gonorrhea many are not aware of the organism Chlamydia, but chlamydia is...

the most common bacterial STD in the world; infecting some 130 million people each year, according to the World Health Organization

Chlamydia organism name

Chlamydia trachomatis

Chlamydia trachomatis morphology

small gram negative short rods obligate intracellular pathogen

true or false: Chlamydia trachomatis has PG

false; no detectable peptidoglycan

many Chlamydia trachomatis strains now identified using what methods?

molecular sequencing; may be associated with specific diseases

Chlamydia trachomatis has a what genome size?

reduced; 1000 kbp (E. coli is 4600 kbp)

Chlamydia trachomatis has how many stage life-cycle?

2 stage life-cycle

Chlamydia is an organisms that has very specific requirements that allows it to exist in...

the cervix, urethra, and fallopian tubes

true or false: Chlamydia can live outside the body

false; Chlamydia cannot live outside the body such as on toilet seats, bath towels or bed linens (often misinformation associated with STDs)

what infection is the most common STD?

cervical infection; estimated 3-4 million US cases costing 2 billion dollars

Chlamydia is most common among...

young people; almost two-thirds of new chlamydia infections occur among youth aged 15-24 years

it is estimated that 1 in how many sexually active young women aged 14-24 years has chlamydia

20

true or false: there is little public perception of chlamydia and the diseases it causes

true

what is trachoma?

chronic disease causing blindness to 6 million; leading cause of preventable blindness