Mini 2 - Fund 2 pt.2 Flashcards
What is the difference between ‘curing’ and ‘healing’?
Curing is eliminating disease, healing is restoring wellness.
What are the two models of health and disease?
Biochemical/naturalist model or Normative model.
Where do the PNS and SNS originate from and what’s the length of the preganglionic fibers?
PNS: craniosacral and long
SNS: thoracolumbar and short
How is choline brought into the axoplasm?
With a sodium dependent carrier. This is the rate dependent step in ACh synthesis.
Where does AChE vs BuChE function?
AChE in cholinergic neurons, NMJ, erythrocytes
BuChE in plasma, liver
Where are M1-M3 found?
All in CNS neurons.
M1 and M3 found in ganglionic neurons, presynaptic terminals, M2 also found in myocarsium and some smooth muscle.
M3 found in smooth muscle, exocrine glands, vascular endothelium.
How are dopamine, norepinephrine, and epinephrine produced?
Tyrosine actively transported to the axoplasm and then is hydrolyzed by Tyr hydroxylase to DOPA (rate limiting step).
Then L-aromatic AA decarboxylase decarboxylates it to dopamine.
In the storage vesicles, it is transformed to NorE by DA-beta-hydroxylase.
NorE is converted to E by phenyl ethanolamine N-methyltransferase (has glucocorticoid cofactors).
What are MAO and COMT?
Catecholamine metabolizers.
MAO found in the mitochondria of neurons, liver, kidney cells and has low substrate specificity. MAO-A preferentially oxidizes indoleamine, MAO-B preferentially oxidizes phenylethylamines.
COMT is located in the cytoplasm of many cells but is relatively scarce in adrenergic neurons - has high substrate specificity.
How are intraneural and extraneural E/NorE metabolized and what are the final metabolites?
Intraneural ones are first deaminated by MAO and then methylated by COMT, extraneural do the reverse order.
Final metabolite is vanillylmandelic acid.
Final metabolite of dopamine is homovanillic acid.
Where are D1 and D2 receptors found beyond CNS neurons? What type of receptor are they?
D1 is found in vascular smooth muscle (renal and mesentaric) and D2 is found in some presynaptic terminals.
D1 is G2, D2 is Gi.
What is an organic vs a functional neuropsychological abnormality?
Organic - structural cerebral or systemic medical pathology.
Functional - psychological or emotional medical pathology.
When is neuropsychological testing not appropriate?
In a period of detox or in an early period of drug abstinence.
How are ADDs generally diagnosed?
Neuropsychological testing not necessary - generally through careful history, structured clinical interviews, rating scales (ratings obtained mostly from parents or teachers).
Common rating scales: Connors rating scale, ADHD symptoms rating scale, Achenbach child behaviour checklist.
What is the MMPI?
Used for assessing psychopathology - answers given as true, false, cannot say - interpretation is driven by patterns of elevations or depressions of scales.
Can be used to screen for substance abuse problems, can help understand how patients are psychologically affected by medical problems, can provide information for how patients are likely to respond psychologically to medical interventions.
What are the Wechsler Intelligence scales?
To judge intelligence (capacity to act purposefully, think rationally, and deal effectively with their environment).
WPPSI (3-7years, 3 months)
WISC (6-16yrs, 11 months)
WAIS (16-89)
Each scale provides verbal IQ, nonverbal/performance IQ, full scale IQ (each has mean 100 and SD 15).
WAIS used in military placement, mental deficiency .
What are the Wechsler Memory Scales?
Used to assess memory and learning in 16-90.
Immediate memory (auditory/visual), General/delayed memory (recognition), working memory
What is endotoxin?
Lipid A - highly conserved (PAMP).
What does pyrogen-free mean?
No LPS.
What is the main role of the O-antigen?
Immune evasion (host mimicry, variation, serum resistance).
How does the LPS trigger immune response?
LBP will bring it to TLR complex, which will trigger a signalling cascade and macrophage activation. THe macrophage will do things, activate cytokines.
Describe the symptoms of endotoxic shock.
Lipid A response. Hypotension, DIC, multiorgan failure, death.
How are bacterial capsules visualized?
Negative staining (methylene blue, maybe india ink), fluorescent antibodies.
How do bacterial capsules trigger immune response?
T-independent B cell activation. The capsule is a repetitive molecule - binds multiple BCRs, activate and get mostly IgM. Soluble IL-4 can aid in proliferation and IgG1 switch.
How do capsules prevent immune killing of the bacteria?
Difficult to penetrate, thick (block receptor binding), often acidic/negatively charged - repel phagocytes.
Some can reduce complement activity - sialic acid binds Factor H (destroys anything complexed with C3b).
What are biofilms? What are the phases of bacteria in a biofilm?
Micro/macrocolonies of bacteria surrounded by matrix of bacterial extrapolymeric substances (EPS) and environmental components (e.g. fibrin).
Most bacterial infections involve biofilms.
Reversible attachment, irreversible attachment, maturation 1 and 2, dispersion.
Cells inside the biofilm are slow growing, have activated stress tolerance genes.
What are superantigens? Give examples.
A type of exotoxin. Links MHCII and TCR in absence of specific Ag (nonspecific T cell activation). Normal signalling cascade in abnormally large number of cells.
Staph. aureus - Staphylococcal enterotoxins, TSSTs.
Streptococcal pyrogenic toxins.
What are cytolysins? Give examples.
A type of exotoxin. Pore forming toxins insert into the membrane, oligomerize and form pores. S. aureus alpha toxin.
Phospholipases are a type of cytolysin. CLostridium perfringens alpha toxin is one.
What are AB toxins? Give examples.
A type of intracellular exotoxin.
A domain is active (toxic anzymatic activity), and B domain is the binding domain (induces endocytosis).
Diptheria toxin - A subunit ADP ribosylates the dipthamide residue on EF2.
Vibrio cholerae ‘cholera’ toxin - A:5B form, A ADP-ribosylates a Gs, resulting in excess PKA, causing too much CFTR activation.
Describe bacterial injected toxins.
A type of intracellular exotoxin. Injected via a type III/IV secretion system. Often has cytotonic effects, changes surface/shape of the cell.
Many will have some kinase activity.
Describe Neisseria meningitidis generally.
“Meningococcus”. 1st/2nd most common cause of bacterial meningitis. Can cause sepsis ‘meningococcemia’. Encapsulated.
Human nasopharynx is its only source - transmission via respiratory droplets or direct contact. Efficient transmission - up to 80% of people in contact with an infected person become carriers. Invasion most common when exposed to new strains (start attending school, go off to live in a dorm, etc.)
Describe the capsule of Neisseria meningitidis.
Capsule helps it survive in the bloodstream - 12 serogroups exist based on capsule structure. B, C, Y, A, W-135 most commonly cause serious disease.
What is the mortality rate of meningococcal sepsis?
100% untreated, 10-15% treated.
What is Waterhouse-Friderichsen’s syndrome?
Adrenal gland failure that may occur in fulminant meningococcal sepsis.
What are the major virulence factors of Neisseria meningitidis?
Type IV pili (coloinze), IgA protease (colonize), OM proteins (invade), Capsule, LOS (produces LOS while alive/intact/growing - blebs - so make a lot more than others).
What skin signs can you see in meningococcal disease?
Mottling, petechiae that can progress to purpura.
Describe the capsule vaccine to Neisseria meningitidis.
Quadrivalent to capsule W-135, Y, A, and C.
Recently a protein-based vaccine against the B serogroup has come out.
What is a distinguishing feature of Pseudomonas aeruginosa infection?
Fruity odour, pigmented visibly blue or green, pus can be coloured.
What are the virulence factors of Pseudomonas aeruginosa besides exotoxins?
Endotoxin, adhesins, biofilm (associated with chronic infection), degradative enzmes, pyocyanin (forms ox. rads, is responsible for pigmentation).
List all the Pseudomonas aeruginosa exotoxins.
Exotoxin A, Cytolysins (PLC, Leukocidin) Type III exotoxins (ExoS, T, U, Y), Exoenzymes (Elastase, alkaline protease).
Describe Pseudomonas aeruginosa exotoxin A.
AB toxin - A subunit acts in same was as diptheria toxin, binds macroglobulin receptor LRP1.
Describe P. aeruginosa ExoS and ExoU.
ExoS alters cell shape, prevents DNA synthesis.
ExoU is a phospholipase - associated with more fulminant, virulent diseas.
Describe P. aeruginosa exoenzymes.
Facilitate spread through tissue. Elastase can do so through lung and can also cause ecthyma gangrenosum (hemorrhagic skin lesions). Alkaline protease can damage tissue and immune cells.
How do you tell if biofilm in a P. aeruginosa infection is mature/late or early?
Late if has Alginate “mucoid polysaccharide”. Linked to severe disease an dissemination.
What type of immunity are IgGs and IgAs good for?
IgGs are good opsonizing Abs, IgAs are good for mucoid immunity.
Describe passive immunization and the types of passive immunization.
Injection of purified Abs or Ab-containing serum into recipient. Rapid, temporary (weeks-months) immunity, gamma-globulin/immunoglobulin is a mix of plasma proteins and broad spectrum of Abs (mainly IgGs) obtained from different donors. Given for disease prevention.
Hyperimmune human Ig preparations have high concentration of antibodies specific for a aprticular pathogen or toxin - given post exposure.
Which pathogens have post-exposure hyperimmune human Ig preparations available?
HepA, HepB, Measles, Rabies, Chickenpox, CMV, Tetanus (human/equine), Botulism (equine), Diptheria (equine).
What are the cons of inactivated vaccines and what sort of agents is it used for? What are the types?
Immunity not life-long, may be only humoral (not cell mediated), local IgA response not elicited, booster shots required.
Used for agents that cannot be attenuated, may cause recurrent einfection, or have oncogenic potential.
Killed, Subunit (polysaccharides can only drive T-cell independent B cell responses - IgG switching only, limited affinity maturation, waning titers after a few months, poor protection to kids under 18 months), Toxoid.
What is a hybrid virus vaccine?
A type of live vaccine where genes from an infectious agent is put into a virus of low virulence.
What are DNA vaccines?
The gene for the protein that elicits the protective response is cloned into a bacterial plasmid that allows for expression of the protein by a human cell - naked DNA is inserted into the muscle or skin and enters the host cell.
They’re good for agents needing T and B cell responses but aren’t appropriate as live vaccines - like HIV and plasmodium falciparum.
What are adjuvants?
A substance that enhances the immunogenicity of antigens. Stimulate APCs (particularly DCs), slow release of Ag to help sustain immune response long enough for effective immunity to develop.
Name the adjuvants in use in the US.
Aluminum salts and gels (only ones in use in Canada), MF59 (oil-in-water emulsion of squalene oil), CpG 1018, A501B (monophosphoryl lipid A and QS-21).
What is a culture?
Sum total of knowledge passed generation to generation in any given society. Includes ideas about illness and healing, exists as an adaptation to or coping with the human condition.
What is an explanatory model?
The way a person explains the cause of illness - why it occurred, what course it’ll take, what treatments are appropriate.
Describe some characteristics of anaerobes.
Lack cytochrome oxidase, reduced/absent detoxification of ROSs, prefer/need low redox potential (Eh/Eo). Many genera ferment acids/alcohols.
What detoxifies ROSs better, an aerobe or a microaerophile?
Aerobe.
How does a facultative anaerobe generate energy?
Aerobic respiration, fermentation, maybe anaerobic respiration.
How do aerotolerant and strict anaerobes generate energy?
Only through fermentation.
Rank a facultative, aerotolerant, and strict anaerobe in terms of who detoxifies better.
Fac > aerotol > strict
What are some sites with normal anaerobic flora?
GI (colon they are 1000x more than aerobic), GU, oropharynx.
Describe Actinomyces.
Gram(+) anaerobe. Filamentous branching rods. Normal in URI, GI, GU. Pyogenic (pus contains yellow granules made of bacteria and neutrophils ‘sulfur granules’).
Describe Lactobacillus.
Gram(+) anaerobe. Normal in oral, GI, GU, common probiotic/rare pathogen.
What are some general characteristics of gram(-) anaerobes?
Often fastidious, slow-growing, stain poorly.
Describe Prevotella and Porphyromonas.
Gram(-) anaerobes. Very small rods, black colonies.
Describe Fusobacterium.
Gram(-) anaerobes. Elongated rods, pointy ‘fusiform’.
Describe Bacteroides spp.
Gram(-) anaerobe. Slender rods/coccobaccilli (can look mixed).
Grow quick on blood agar, bile resistant, hydrolyze esculin, SOD(+), catalase (+).
Antibiotic resistance common. Virulence factors: pili, polysaccharide capsule. Lipid A not very pyrogenic.
Describe Bacteroides fragilis.
Gram(-) anaerobe. Most commonly isolated organism in intraabdominal infections/abscesses. BFT toxin (metalloprotease, degrades E-cadherin, stimulates fluid loss in intestine, IL-8 production, oncogenesis(?)).
How do IC bacteria get into cells? Name some examples for the methods.
Phagocytic cells - via phagocytosis (PAMP recognition).
Nonphagocytic cells: Zipper mechanism (tricks host cell into wanting to adhere via adhesin expression) (Listeria, Yersinia, Campylobacter, Helicobacter).
Trigger mechanism (hijacks cytoskeleton - bacterial type III/IV secretion system injects effectos into host cells which stimulates actin and other cytoskeletal components to form protrusions/endocytic vesicles) (Salmonella, Shigella, Chlamydia).
Name the obligate intracellular bacteria.
Rickettsia, Orientia (vacuolar - stay in phagosome, prevent lysosome fusion), Chlamydia, Chlamydophilia, Ehrlicia, Anaplasma, Coxiella, some mycobacteria (cytosolic/nuclear).
Can Orientia and Rickettsia make ATP?
Yes, or they can steal the host’s.
What are the two forms of vacuolar intracellular bacteria?
Reticulate body - metabolically active, non infectious, forms inclusion body, fragile.
Elementary body - inactive but infectious; tough.
What’s special about Chlamydia and Chlamydophilia?
Protein cell wall, don’t make ATP, don’t make NAD.
Legionella pneumophilia - describe its morphology, characteristics, growth requirements, reservoir, and what diseases it causes.
Gram(-) rod (may be more coccobacillary in tissue), poorly staining (can stain with Dieterle silver), thin, motile, non-fermentative, oxidase(+), catalase(+), only uses AAs, needs BCYE agar (L-cys, Fe3+, oxygen), slow growing 2-5d.
Reservoir is amoebae in freshwater, causes atypical pneumonia (Legionnaire’s), Pontiac Fever - in immunocompromised hosts.
Describe infection and pathogenesis with Legionella pneumophilia. How is it diagnosed?
Inhaled, wants to be in macrophages (can also infect alveolar epithelial cells and monocytes). OMPs bind alveolar macrophage complement receptors via C3b or directly. Several surface proteins including Mip (macrophage infectivity potentiator) enhance phagocytosis).
Once in, type IV secretion system secretes enzymes that hijack vesicle trafficking/ Phagosome recruits the ER which prevents lysosome fusion. This causes apoptosis.
It’s diagnosed with urine antigen but only detects the most common serotype.
What is the morphology of Listeria monocytogenes?
Gram(+), weakly beta hemolytic, nonspore forming rod, can tolerate salt and pH extremes, replicates at 4Celsius. Catalase (+). Distinctive tumbling motility.
How is Listeria monocytogenes taken in and what can it cause?
It is ingested through contaminated food. It can cause sepsis, meningitis. Primarily in immunocompromised hosts.
It can cross the placenta.
What is the pathogenesis of Listeria monocytogenes?
Enters phagocytes by phagocytosis, non phagocytes by Zipper mechanism. Internalin A binds E-cadherin, Internalin B binds c-Met.
The drop in pH activates 2 PLCs and listeriolysin O (LLO) - pore forming toxin. It escapes into the cytosol and then surface protein ActA polymerizes actin at one pole and pushes it along.
Describe the morphology and growth requirements of Coxiella burnetti. What illnesses does it cause and how is it transmitted?
Microaerophile, gram(-) but stain poorly, need BL3 lab to culture.
Causes Q fever (interstitial pneumonitis) via inhalation of particles or zoonosis.
Describe the pathogenesis of Coxiella burnetti.
Small cell variant (SCV) is resistant, inert environmental form (stealth pathogen). Binds macrophage integrin involved in apoptosis, not surface receptor for pathogens, Lipid A acts as TLR4 antagonist.
Endosome acidifies, it activates into LCV/CCV (Coxiella-containing vacuole). Survives phagolysosome, injects proteins to delay apoptosis via type IV secretion system.
How do you determine if something is a HAI/nosocomial infection?
Appears at least 48 hours after admission or less than 48 hours after discharge.
What does ‘iatrogenic’ mean?
Infections caused by physician (includes healthcare measures in general).
What makes up 85% of nosocomial infections?
UTI, SSI, pneumonia, BSI, GI, CDAD.
What are the most lethal HAIs?
Pneumonia, bacteremia.
