Microbio 2 Flashcards
1
Q
definitive host
A
harbors the adult/sexually mature stages of parasite (or in whom sexual reproduction occurs)
2
Q
intermediate host
A
harbors the larval/sexually immature stages of parasite (or in whom asexual reproduction occurs)
3
Q
permanent parasite
A
lives in (endo) or on (ecto) host without leaving (e.g., lice)
4
Q
opportunistic parasite
A
capable of producing disease in an immunodeficient host, found in latent form or causes a self-limiting disease (i.e., cysts remain dormant until immunosuppressed, then travel and cross blood-brain barrier to form in brain)
5
Q
what are 5 types of parasitic transmission?
A
- direct ingestion of infective larvae, eggs, or cysts
- ingestion of intermediate host
- penetration of the principle host
- maternal transmission
- vector borne
6
Q
what is IgE and what is it’s role in parasitic diseases
A
- immunity to parasites (helminths)
- IgE antibody levels are often high in people with allergies, may be increased in autoimmune diseases
- total IgE test sometimes used as screening test if a parasitic infection is suspected
7
Q
helminthic therapy
A
using worms to treat immune-mediated disease; epidemiological studies suggest that people who carry helminths have less immune-mediated disease
-reduce disease activity in patients with ulcerative colitis or crohn’s disease
8
Q
what are some of the strategies used by parasites to evade host defenses?
A
- complicated lifecycle: affective immune response difficult because host may be harboring several different stages of parasite
- antigenic concealment: intracellular survival within macrophage
- antigenic variation: gene switching
- antigenic shedding: shedding of surface antigens or components
- antigenic mimicry: incorporation of host “self” antigens into parasite surface
- immunological subversion
- immunological diversion
9
Q
sCJD
A
- usually white geriatrics, mostly sporadic infection
- NOT transmitted p2p
- complete dimension by 6th mo., death in a year
- brain biopsy: spongiform change, neuronal loss without inflammation, accumulation of PrPsc
- PrPsc deposition is diffuse
10
Q
vCJD
A
- mad cow; median age is 29
- type 4 PrPsc
- bovine to human and p2p by blood or food contaminated with BSE (NOT milk or muscle)
- slower progression of dementia
- peripheral pathogenesis in lymphoid organism
- florid PrPsc plaques consisting of round amyloid core surrounded by ring of spongiform vacuoles
11
Q
what is a virion vs. virus?
A
- virion: virus particles, inert carriers of the genome that are assembled inside cells from virus-specified components; they do not grow and form by division
- virus: capsid-encoding organism; infected cell
12
Q
what is the structure of a virion?
A
genome + capsid +/- envelope
- modular genome: encodes for capsid proteins, replicon, and host cell interacting factors
- capsid: can be icosahedral, helical, or complex in symmetry; shape independent of genome
13
Q
cytopathic effects
A
visible effect of viral infection; cells breakdown/morph
-not all viruses cause CPE but it can be used to study replication and infectivity
14
Q
what are the requirements for viral replication?
A
- right host (trophism)
- susceptible cell (right receptors)
- permissive cell (appropriate intracellular environment
- biosynthesis machinery
- abundant building blocks
- time to finish
15
Q
what are the general steps of virus replication?
A
- recognition
- attachent
- entry
- uncoating
- transcription of mRNA (RDRP or RT)
- protein synthesis by host machinery
- replication of genome (RDRP, viral DNA pol, or host DNA pol or RNA pol II)
- assembly of visions
- egress
16
Q
describe the single step viral growth curve
A
- eclipse: no virus recovered during the replication and assembly phase
- maturation and release: virus particles are made and can infect cells
- burst size: # of infectious progeny from a single round of replication; difference between what you put in and what you get out, distinctive for that virus
17
Q
general scheme of RNA virus replication
A
- recognition and unpacking
- transcription
- replication with RNA-dependent RNA pol (all RNA viruses have, either package in virion or encoded)
18
Q
RNA-dependent RNA Pol
A
highly efficient, low fidelity enzyme that catalyzes the replication of RNA from an RNA template
-functions in cytoplasm (except influenza)
19
Q
Polio
A
+ssRNA genome, linear mRNA molecule
- enterovirus, adapts in vivo to affect muscles and nerves (flaccid paralysis)
- fecal-oral transmission
- vaccination with live or attenuated virus
- entry: changes shape after binding to receptor, capsid proteins become hydrophobic and form pore through membrane
- RDRP copies + and - strands
- translation happens first when RDRP is scarce
- collisions occur between RDRP and ribosomes
- RNA synthesis occurs later when RDRP is abundant
20
Q
Rotavirus
A
dsRNA, reovirus, segmented, naked isocahedron
- severe gastroenteritis
- RDRP in virion first transcribes mRNA
- egress via exocytosis (membrane vesicles) or cell lysis
- virions mature in gut lumen and infect more enterocytes or are shed in profuse diarrhea
- ORS
- live attenuated vaccines
21
Q
Influenza
A
- ssRNA, segmented, primarily in lung
- sements traffic to nucleus for transcription and translation
- egress by budding
- Neuraminidase (N antigen) releases virions from sialic acid on cell surface
- antivirals: tamiflu and relenza (sialic acid analogs; virions remain attached to cell which stops spread)
- vaccines: trivalent inactivated vaccine
22
Q
HIV
A
+ssRNA
- virion fuses with plasma membrane, reverse transcriptase converts +ssRNA into dsDNA which integrates into host chromosome for life
- host RNA pol II transcribes mRNA from integrated genome
- viral proteins bud from plasma membrane
- virion maturation occurs outside cell
- serologic assays for antibodies, CD4 T cell counts, nucleic acid assays for viral load
- treatment to suppress viral load, restore immune function, prevent drug resistance, and improve QALY
- meds: AZT (thymidine analog; chain terminator); stribild (4 drug combo; includes cobiscistat: targets host cell enzyme in liver that breaks drugs down)
23
Q
general scheme of DNA virus replication
A
- transcription and translation in nucleus (except pox)
- host RNA pol transcribes mRNA (except pox)
- both cellular and viral TFs regulate
- viral or host DNA pol replicates genome
24
Q
Adenovirus
A
- linear dsDNA
- respiratory
- fecal-oral and aerosol transmission
- susceptible populations: kids and military
- capsid–>NPC–>DNA uncoats through nuclear pore–>host RNA pol II makes mRNA, (TFs first, then amplification)–>genome replication by viral DNA pol–>virions egress by lysis
- treat with cidofivir (just dire cases, nephrotoxicity)
25
Q
Papillomavirus
A
- circular dsDNA
- most commonly diagnosed STI
- host RNA pol transcribes viral mRNA
- host DNA pol synthesizes viral genomes
- viral factors E6 and E7 are oncogenes
- vaccines with virus-like particles
- diagnose with DNA tests, treat with oncotherapy or excision
26
Q
Herpesvirus
A
-linear dsDNA
-envelop and tegument; dense body = only tegument, no capsid
-big genome (5x bigger than adeno)
-tegument into cytoplasm to modify host cell
capid–>NPC–>DNA uncoats through nuclear pore
-immediate early genes (TFs)–>early gene (replication)–> late proteins (structure proteins)
-capsids assemble in nucleus and bud through nuclear pore
-latency in genome for the life of infected person
-treatment: acyclovir (guanosine analog; chain terminator)
27
Q
HSV1
A
- primary: gingibostomatitis
- recurrent: prodrome precedes lesions
- latency in dorsal root ganglia
- infection can cause meningitis
- PCR to distinguish between HSV1 and HSV2
28
Q
HSV2
A
- contagious vesicular lesion below waist; asymptomatic shedding
- latency in dorsal root ganglia
- PCR to distinguish between HSV1 and HSV2
- infection can cause meningitis
- chemoprophylax with valtrex or famvir
29
Q
VZV
A
- primary: chicken pox
- recurrance: zoster/shingles
- latency in dorsal root ganglia
- aerosol transmission
- outbreak out of 1 neuron (single dermatome)
- vaccine: live attenuated virus
30
Q
EBV
A
- mono (severe sore throat)
- latency in B cells
- transmission through saliva
- recurrance is rare: lymphoma (e.g. burkitt’s)
- diagnose based on serology and blood smear
31
Q
CMV
A
- primary: asymptomatic or diagnosed (splenomegaly, rash, jaundice); mono like but no spore throat
- latent in bone marrow
- frequent cause of transplant failure
- congenital CMV causes hearing loss and developmental disabilities
- treatment: ganciclovir (guanosine analog; recognized by host DNA pol, highly toxic)
32
Q
HHV6, HHV7
A
- roseola infantum; 3 day high fever followed by noncontagious rash on trunk
- transmission through saliva
- peak incidence 7-13 mo
33
Q
HHV8
A
- kaposi sarcoma
- primary: inapparent
- infectious cancer associated with age and immunosuppression (treat immunosuppression and cancer goes away)
- highly vascularized tumors
34
Q
characteristics of viral genomes
A
- eukaryotic (all genes are single units)
- TFs bind to enhancer/promoter and regulate
- reading frames can overlap on the same strand (express 2 different proteins at once)
- ribosomal frame shifting changes amino acid sequence
- alternative splicing of RNA changes amino acid sequence
- expression of polyproteins: create multiple proteins from 1 promoter by cutting big mRNA with viral protease
- frequency of mutation is high
35
Q
types of virus interactions
A
- interference: blocks receptors, competes for resources, produces interferon or other anti-viral genes
- complementation: gene function of one virus replaces mutated or missing gene of another
- phenotypic mixing: similar viruses can exchange cupids, pseudo type created can’t replicate or grow
- recombination: viruses with similar genomes can exchange genes by crossing over at homology; new hybrids can grow and replicate
- reassortment: rearrangement of segments to form new ones; very rapidly changes the virus (antigenic shift)
36
Q
gene therapy
A
- delete essential gene from virus and insert that gene into complementing cell, clone therapeutic human gene into complemented cell line, and grow
- monogenic disorders might be abled to be treated (ex. retinoblastoma, hemophilia)
- problems associated: short duration of expression, low efficiency of gene transfer means high dose of virus, inflammatory response to virus vector
37
Q
primary viremia
A
viruses spread from surface of body to lymph node and blood stream
38
Q
secondary viremia
A
second time virus is detectable in the blood, disseminates virus to organs where it is shed
39
Q
pathogenesis of chicken pox/shingles
A
- primary viremia: respiratory route to lymph node
- secondary viremia infects epithelial cells and causes lesions
- latency established simultaneously in dorsal root ganglion
40
Q
modes of viral transmission
A
- respiratory
- fecal-oral
- contact
- zoonoses
- blood
- sexual
- maternal-neonatal
- genetic (prions and retroviruses)
41
Q
patterns of viral disease
A
- acute: disease occurs and resolves (ex. common cold)
- latent: acute episode then virus is undetectable/noninfectious then second disease episode (ex. varicella/zoster)
- chronic: virus acquired, potential acute episode, then virus maintains detectable level with shedding throughout life course (ex. hep B and C)
42
Q
how do viruses injure host?
A
- directly: any virus that gets out of the cell by lysis (ex. norwalk and respiratory syncytial virus)
- indirectly: host response to infection (interferon response)
- successful virus will avoid destruction by immune system and avoid destroying host before replication is finished
43
Q
Hep A
A
- picornavirus: RNA, no envelope
- transmission: fecal-oral
- vaccination: raises IgG response, protective against reinfection
- virus itself is not hepatotoxic, symptoms are largely immunogenic (worse in adult than child)
- diagnosis: elevated ALT, IgM (acute), IgG (recovered/vaccinated)
44
Q
Hep B
A
- hepadnavirus: DNA, envelope
- transmission: sex/birth/bood
- virus itself is not hepatotoxic; produces immunological decoys (viral protein) that ties up antibodies
- antibody-antigen complexes in blood try to pass through capillaries (cause joint pain because of deposition)
- carries RT and replicates through RNA intermediate
- vaccination
- diagnosis: biopsy (“ground glass”), serology of viral surface antigen (acute), IgG against viral surface antigen (recovered/vaccinated)
- most hepB resolves, can cause chronic hepatitis and/or hepatocellular carcinoma
- treatment: tenofovir: designed for HCV and HIV (targets RT); pegylated interferon; entecavir (guanosine analog)
45
Q
Hep C
A
- flavavirus: RNA, envelope
- transmission: sex/birth/blood
- highly mutagenic
- acute infection similar to HepB but no decoys (less likely to raise a strong immune response)
- higher rate of chronic hepatitis leading to cirrhosis and/or cancer
- diagnosis: elevated ALT, EIA (real or false positive, follow up with RIBA); screen for HIV, hepB, and drug abuse
- no vaccine (IgG not protective)
- treatment: pegylated interferon, sofosbuvir: uridine analog (inhibits RDRP), telaprevir (inhibits NS3.4A protein in replication complex)
46
Q
antiviral methods of action
A
- nucleoside analogs: genome replication
- non-nucleoside analogs: genome replication
- protease inhibitors: assembly and release
- entry inhibitors
- many drugs are competitive inhibitors (reversible); rebound can occur
47
Q
potential resistance to antivirals
A
- mutations often exist in patient before drug is administered (drug treatment selects for resistant virus strands)
- resistance occurs because of high rate of virus replication, high mutation rate, high selective drug pressure, immunosuppressed host
- counteract by combining drugs with different targets; targeting host functions (beware of toxicity), and alleviating immunosuppression to antivirals
48
Q
broad spectrum DNA antivirals
A
foscarnet and cidofavir (both are toxic to kidneys)
49
Q
broad spectrum RNA antivirals
A
ribavirin (guanosine analog): targets RDRP enzyme, can immunomodulate (change T cell profile), lowers GTP in cell
50
Q
properties of fungi
A
- eukaryotes
- chitin and ß-glucan cell wall
- cell membrane has ergosterol (not cholesterol)
- no endotoxins, mycotoxicosis: fungal poisoning after ingestion
- aflatoxins: mutates p53, linked to hepatic carcinoma
- fungal allergies
- yeasts (single cell; budding) or mold (multicellular; hyphae form mycelium; most are asexual–5 types of conidia: spores with distinctive microscopic appearance)
- thermal dimorphism: mold in environment, yeast in body
- immune response: granulomatous and/or supporative
51
Q
diagnosis of fungi
A
- PPD
- direct microscopy: KOH mount microscopy with final stains
- culture on sabouraud’s agar
- PCR available for dangerous systemics
- serology for epidemiology
52
Q
fungal treatments
A
- polyenes: binds ergosterol; broad spectrum disrupts cell membranes (ex. amphotericin B: systemic and nephrotoxic, only antiviral safe for pregnancy)
- azoles: inhibit ergosterol synthesis (ex. fluconazole/diflucan for candidiasis and cryptoccosis)
- echinocandins: inhibis ß-glucan synthesis (effective against candida and aspergillus)
53
Q
four major categories of fungal infections
A
- superficial
- subcutaneous
- systemic
- opportunistic
54
Q
superficial fungal infection
A
- minor infections or overgrowth on superficial skin layer
- does not require thermal dimorphism
- symptoms: itch or discoloration
- treatment: topical azoles or oral griseofulvin if necessary
- ex. dermatophytosis
55
Q
subcutaneous fungal infection
A
- granulomatous infection of low dermal layers
- requires thermal dimorphism
- trauma exposes subcutaneous tissue to soil or vegetation
- treatment: oral azoles, amphotericin B and local surgery
- ex. sporotrichosis
56
Q
dermatophyosis
A
- transmitted by fomites or auto inoculation
- very common; minor symptoms (called tinea)
- infect only superficial keratinized structures
- diagnosis: KOH mount, culture
- treat: affected body sites simultaneously with topical antifungal
57
Q
sporotrichosis
A
- caused by sporothrix spp; thermally dimorphic fungi
- enters through thorns
- painless ulcer spreads through lymphatics over the years
- if immunocompromised there can be disseminated symptoms or meningitis
- diagnosis: biopsy and culture at room temp from pus
- treat: oral azoles, amphotericin B for more serious forms
58
Q
systemic fungal infection
A
- infection spreading from inhaled spores
- thermal dimorphism, NO p2p
- range of severity
- most common is coccidioides/histoplasma/blastomyces (mimic TB but source is American dirt)
59
Q
coccidioides
A
- thermally dimorphic (mold/spherule) endemic to US southwest
- mold grows in wet weather, releases arthrospores in drug weather
- 60% mild (asymptomatic or flulike; clearance by CMI), moderate (valley fever/desert rheumatism; pulmonary and EN), severe: major pneumonia or dissemination
- diagnosis: exam, history, ppd, biopsy for spherules, culture, serology
- treatment: if predisposed to complications (oral azoles), meningitis (fluconazole), pregnant/disseminated (ampho. B)
60
Q
opportunistic fungal infection
A
- diseases and severity are widely varied, predicated on patients’ pre-existing conditions
- optimal treatment addresses infection and underlying problem
- ex. cryptococcosis
61
Q
cryptococcosis
A
- enabled by reduced CMI, blunted inflammatory response complicates diagnosis
- dimorphic BUT NOT thermally dimorphic
- presents late in disease with meningitis (subacute) and skin nodules or pulmonary symptoms
- No p2p except organ transplantation
- steroids, AIDS, and survival with malignancy have increased caseload
- diagnosis: biopsy, CSF, crag (crytococcal antigen in blood and CSF)
- treatment: pulmonary may not need treatment, meningitis or cryptococcoma (localized, solid, tumor-like masses) require combo of azoles and ampho. B
