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microbio 4

Terms

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Give definitions of the following:
Yeast
Hyphae
Molds
Spores
Dimorphic fungi
Saprophytes
Yeast- unicellular growth form of fungi. Spherical to ellipsoidal.
Hyphae- Threadlike, branching, cylindrical, tubules composed of fungal cells attached end to end. These grow by extending in length from the tips of the tubules.
Molds- Multicellular colonies composed of clumps of intertwined branching hyphae. Molds grow by longitudinal extension and produce spores
Spores- reproducion bodies of molds
Dimorphic fungi- can grow as either a yeast or mold
Saprphytes- Fungi that live in and utilize organic matter
What is the essential sterol of the fungal cell membrane and how do amphotericin B and nystatin fight it?
Ergosterol is the essential sterol.
amphotericin B and nystatin bind and punch holes
ketoconazole inhibits synthesis.
Define the roles of the Capsule and Cell wall of fungi.
Cell Wall- mostly carbs w/ some protein. Ags to the immune system
Capsule- Polysaccharide coating. India Ink helps visualize
What does Malassezia furfur cause?
Tina versicolor
Hypopigmented or hyperpigmented patches on the skin.
What is caused by Exophiala werneckii?
Tinea nigra
Superficial fungal infection that causes dark brown to black painless patches on the soles of the hands and feet.
How do you diagnose and treat Tinea versicolor and nigra?
Microscopic exam of skin scrapings mixed on a slide with KOH. Will reveal hypae and yeast. Spagetti and meatballs.
Rx- selenium sulfide (dandruff shampoo) over the skin. Topical imidazoles
What do the dermatophytes cause?
(Microsporum, Trichophyton, Epidermophyton)
Scaling of skin, loss of hair, crumbling of nails Keratinase. Pruritic lesion with central clearing

Tinea corpis- body
Cruris- jock
pedis- foot
capitus- scalp
unguium- nail
How do you Dx dermatophytosis?
Dissolve in KOH, branched hyphae.
Wood's light, uv 365. Floresces green.
How do you Rx dermatophytosis?
topical imidazole
What cutaneous infections does Candida Albicans cause?
Oral thrush, diaper rash, Candida vaginitis
What does sporothrix schenckii cause?
Think roses, gardeners
Found in soil and on rose thorns. Sporotrichosis
ulcer, resolves, new nodules pop up along lymph.

Microscopic- yeast that reproduce by budding- culture at 37=yeast. 25=branching. Unequal budding

Rx- K-iodine
What causes chromoblastomycosis?
copper-colored soil saprophytes
Pialophora Cladosporium
Rotting wood.

Infection iwth a puncture wound. Small violet wart-like lesion (look like cauliflower)
Coccidiodomycosis, Histo, Blasto, para coccidiodo, where do you find them?
Coccidiodo- Southwest U.S., Cali
Histo- Ohio, Mississippi River Valley
Blasto- East of Mississippi River
Paracoccidiodo- rural latin america
What is the mechanism of disease in Histo, Blasto, Coccidiodo?
all are dimorphic fungi (coccidiodes is spherical in tissue, but the others are yeast.
Inhalation of a spore from soil, bird poo, or vegetation, not person to person

local infection of the lung-> dissemination
What are the different presentations of Histo, Blasto, and Coccidio?
Asymptomatic- majority
Pneumonia- mild, fever, cough, chest X-ray infiltrates. Can have granulomas. Some can develop chronic cavitary pneumonia.
Disseminated- Rare, but can cause meningitis, lytic granulomas of th ebone, skin granulomas.
How do you Dx Blasto, histo, coccidio?
biopsy, silfver stain or Sabouraud's agar
How do you Rx blasto, histo, coccidiodo?
itraconazole or amphotericin B
Blasto requires aggressive treatment.
What are some differenced between Histo, Blasto, Coccidiodo?
Histo- bird and bad droppings, cleaning chicken coops or spelunking
Blasto- soil and rotten wood, rarely systemic, but when it does, it is worse. Broad based budding
Coccidioides- mild pneumonia, but opportunistic in AIDS. Sheerule with endospores.
What is the disease of cryptococcus?
Cryptococcus- polysaccharide encapsulated yeast.
inhaled, asymptomatic. Narrow based budding, capsular halo. Latex agglutination with polysaccharide capsule.

major manifestation is meningoencephalitis. Peigeo droppings.

AIDS
What is the Rx for Cryptococcus?
amphotericin B and flucytosine for 6 mths
What is the role of Candida Albicans, clinically in a normal host?
Oral thrush- patches of creamy white exudate with a redding base over the mucous membranes.
Rx- nystatin or amphotericin B (swish and spit), or imidazol candy

Vaginitis- more often with abtics, ocs, menses, preggers. Vaginal itching and discharge. Cottage cheese appearing vaginal wall.
Rx- Imidazole suppositories (vaginal)

Diaper rash- red, macerated
What is the role of Candida Albicans, clinically in an immunocomprimised host?
Esophagitis- thrush in the esophagus. substernal pain, pain on swallowing

Disseminated- blood to every organ. Examine retina. isolation from the blood is never normal. Dx with KOH
Rx- Amphotericin B or oral imidazole- fluconazole
What is the role of Aspergillus, clinically?
People can develop an IgE reaction to aspergillus spores. Or Delayed type. Corticos are good.

For lung cavitations from TB or maligs- gungal ball in the cavity called aspergilloma.

Immunocompromised can develop invasive pneumonieas and disseminated disease.
What are the toxins of fungi?
mycotoxins- cause liver damage and liver cancer

aspergillus- aflatoxin
What are the two forms of candida?
budding yeast at 25
germ tubes at 37
What is mucormycosis?
mold with nonseptate hyphae branching at wide angles.
ketoacidotic diabetic and leukemic pts. Fungi proliferate in the walls of blood vessels and cause infarction of distal tissue. Rhinocerebral frontal lobe abcess.
Pneumocystis carinii
causes diffuse interstitial pneumonia. Yeast, inhaled.
Immunosuppression predisposes, Dx by biopsy or lavage. Methenamine silver stain of lung tissue.
Rx- TMP-SMX, pentamididne, dapsone. Prophylaxis at <200cells/mL
What are the SEs of amphotericin B?
Renal toxicity- dose dependant, reversible; hydration helps. Loss of e-lytes as well. New fatty mixtures decrease

Acute Febrile Reaction- a shaking chill with fever after IV infusion. Common. Given with anti-pyretic.

Anemia
Inflammation of the vein
What is the mechanism of amphotericin B?
binds to ergosterol in the membrane-> osmotic lysis
What's the issue with Nystatin?
can't be used systemically too toxic. Used swish and swallow, topical for diaper rash/vaginal candidiasis
What is the mechanism of Flucytosine?
inhibits DNA/RNA synthesis
What are the SEs of Flucytosine?
Bone Marrow depression, nausea, vominting, diarrhea
What is the mechanims of the Azoles?
inhibit cytochrome p450 involved in ergosterol synthesis. disrupts permeability.
Which two azoles are too toxic for systemic use?
Clotrimazole, Miconazole
What are the SEs of Ketoconazole?
GI- nausea, vomiting, anorexia
Hepatotoxicity- temporary rise of hepatic enzymes, and maybe necrosis
Inhibition of testosterone synth.- gynecomastia, impotence, decreased libido, decreased sperm
Adrenal suppression
What is ketoconazole used for?
mucocutaneous candidiasis
What is the role of Fluconazole?
less toxic and more broad than ketoconazole. Maintenance for AIDS pts with cryptococcus infection.
clears candida very well.
What is the role of Itraconazole?
very broad and good.
1st line for chromoblasto, histo, coccidioido, blasto adn maybe aspergillosis
what is the role of Voriconazole?
aspergillosis
What is the mechanism of Griseofulvin?
disrupts spindle formation to prevent mitosis. Deposits in keratin precursor cells to inhibit growth. Does not kill. Used for dermatophytes (tinea...)
What are the SEs of Griseofulvin?
teratogenic, carcinogenic, confusion, headaches, increased warfarin metabolism.
What is the role of K iodide?
Treats sporotrichosis unless it is systemic.
What is the role of Terbinafine?
oral fungicidal agent that blocks cell wall synth. Blocks ergosterol synth. Inhibs formation of squalene epoxide. Acumulates in nails.
Breakdown Capsofungin:
Mechanism
Use
Tox
Mech- inhibs cell wall synth
use- aspergillosis
tox- GI upset and flushing.
What DNA virus is not dsDNA?
Parvovirus(ssDNA)
What DNA viruses are not linear?
papovaviruses, hepadnaviruses
What RNA virus is not ssRNA?
Reoviridae (dsRNA)
What viruses are not haploid?
retroviruses (diploid)
What DNA virus is not icosohedral?
Pox
What DNA virus does not replicate in the nucleus?
Pox- has it's own RNA polymerase
What DNA viruses are naked?
PAP
Parvo
Adeno
Papova
What DNA viruses are enveloped?
Hepadna, Pox Herpes
What RNA viruses do not replicate in the cytoplasm?
influenza- orthomyxo
retroviruses
What is the difference between + and - RNA?
+ means mRNA- immediately translated
- means they must be transcribed into an mRNA first- usually with an RNA-dependent RNA polymerase (virus must carry its own)
What are the roles of + and - strands in DNA viruses?
+ are read-> mRNA
- are ignored
they have both.
What type of nucleic material is found in helical capsules?
What virus does not assume a shperical shape with a helical capsule?
RNA

Rhabdovirus (Rabies)- bullet shaped
Which RNA viruses are non-enveloped?
PCR
Picorna
Calici
Reoviridae
What 5 viruses are icosohedral?
Reo
Picorna
Toga
Flavi
Calici
What are the steps of viral replication?
Adsoprtion and penetration
Uncoating
Synthesis and assembly (inhibition of cell)
release of virions- lysis or budding
How do viruses exit the cell?
non-enveloped- lyse
enveloped- bud
What are teh roles of:
Hemagglutinin
Neuroaminidase
M protein
HA- attaches to host sialic acid receptor (adsorption)
NA- cleaves neuroaminic acid, disrupts mucin barrier
M-protein- anchors NA, MA
What is Reye's Syndrome?
Kids with the flu, who are given aspirin, can get severe liver and brain disease.
How do you Rx the flu?
Vaccine
Amantadine, Rimantidine- prevent uncoating of flu A.

Sanamavir and oseltamivir are NA inhibitors which can shorten the coarse of disease
What is the difference between live attenuated viruses and killed vaccines?
What are the live?
what are the killed?
What are the egg-based?
what are the recombinant?
Live- humoral and cell immunity
Killed- only humoral

Live- MMR, Polio, VZV, yellow fever, smallpox, adenovirus
Killed- Rabies, flu, HAV, Salk polio
Egg-based- FRY Flu, MMR, Yellow fever
Recombinant- HBV
Define the following:
Recombination
Reassortment
Complementation
Phenotypic mixing
Recombination- exchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology
Reassortment- viruses with segmented genomes exchnage segments. High frequency recombination. (flu pandemics)
Complementation- 1 virus has a non-functioning mutated protein. The functioning viruse makes up for it.
Phenotypic mixing- Virus A can be coated with proteins of virus B. Infectivity properties of B, disease of A.
Which viruses are segmented?
BOAR
Bunyaviruses
Orthomyxoviruses
Arenaviruses
Reoviruses
What type of virus is Paramyxoviridae?
(-) strand RNA, single strand
HA and NA are a part of the same glycoprotein spike, not 2 different spikes
fusion protein that causes the infected host cells to fuse toghether inot multinucleated giant cells
What are the four paramyxoviridae viruses?
parainfluenza
respiratory syncytial virus
mumps
measles

Lungs- all adsorb to and replicate in the UR tract.
Kids. (RSV and paraflu- LR in kids, UR in adults)
viremia- viral infection results in disseminated virions. distant organs (mumps- orchitis, parotitis)
What does Parainfluenza cause?
UR in adults
Kids, elderly, immuno- lowr resp- pneumonia
Croup- paraflu of the larynx. stridor and barking.
How do you prevent RSV?
palivizumab (Ab produced by recombinant DNA)
infants
What antigens are not present on RSV?
HA and NA
does have F-protein->syncytial cells
What is the measles prodrome?
conjunctivitis, swelling of the eyelids, photophobia, high fevers, hacking cough, rhinitis and malaise.

Koplik's spots- red-based clesion with blue-white center.
Describe the measles' rash
red, flat, bumpy. forehead to the face, neck and torso. feet by 3rd day. Disappears in the same way.
What are some of the complications of measles?
pneumonia, eye damage, heart involvement, and encephalitis. Rare, but kills.
What is subacute sclerosing panencephalitis (SSPE)?
Slow form of encephalitis caused by measles. years after infection-> slow progressing CNS diseases. mental deterioration, incoordination
how many serotypes do the paramyxos have?
RSV, measles, mumps 1
paraflu 4
HAV:
what kind of virus?
how is it transmitted
incubation?
picornavirus
fecal-oral
3 wk incubation
Asymptomatic, Alone (naked), Acute
HBV:
what kind of virus?
how is it transmitted
incubation?
DNA hepadnavirus
parenteral, sexual, mom-fetus
3 month incubation
DNA-dependant DNA polymerase
HCV:
what kind of virus?
how is it transmitted
incubation?
RNA flavivirus
blood
similar to HBV
IV drug use
Chronic, Cirrhosis, Carcinoma, Carriers
HDV:
what kind of virus?
how is it transmitted
delta agent- requires HBsAG as it's envelope
HEV:
what kind of virus?
how is it transmitted
incubation?
RNA calicivirus
enterically (HAV)
preggers need to watch out
What does the HBeAg mean?
transmisibility
presence of HBeAb means low transmisibility
What is the Pathogenesis of HBV?
Acute hepatitis
Fluminant- sever acute hepatitis with rapit descruction
Chronic
- aysmptomatic carrier- never develops Abs. No liver injury
- chronic-persistent Hepatitis- low-grade smoldering hepatitis
- chronic active- patient has an acute hepatitis state w/o normal recovery

Immunosuppressed are more likely to be carriers
How do you treat HBV?
Lamivudine- suppresses DNA
IFN alpha- suppresses 50%
What is the relationship between retroviridae and oncogenes?
many retroviridae cause leukemia or sarcoma in hosts.
DNA gets incorporated into host.
Most need a co-infecting virus to cause cancer as they have lost the RNA. THe Rous sarcoma virus is the only known acute virus that is nondefective.

Non-acute transforming viruses don't encode the full oncogene, just promote.
What is the structure of HIV?
Diploid genome (2 molecules of RNA)
Nucleocapsid proteins bound to the RNA and 3 retroviral enzymes. Protease, reverse transcriptase and integrase
Icosohedral capsid. p24
surface glycoproteins- gp 120 and 41
What are some parts of the HIV Genome?
all retros- two long terminal repeats- sticky ends, pomotoer/enchancer
Gag- code for proteins inside the envelope, nucleocapsid, capsid, p24, matrix proteins. (structural)
Pol- protease, integrase and reverse transcribtase.
env- envelope, gp 120 and 41
What are the regulatory proteins of HIV?
tat- viral transactivator- binds and activates transcriptioin.
rev- revs up viral activity. prevents splicing to increasae production of gag, pol, and env
nef- uncertain, but + and - regulates HIV
How do you diagnose HIV infection?
ELISA- sensitive- high false + and low threshold, RULE OUT
postives confirmed with Western Blot RULE IN

can be falsely negative in 1st 2 months. falsely + in babies born to moms with HIV.
AIDS=<200 CD4 or CD4/CD8 <1.5
HIV immunity???
CCR5- Homozygous=immunity
heterozygous=slow course
CXCR1- rapid
What happens if the CD4 count drops to 400-200?
constitutinal symptoms, skin infections, athlete's foot, oral thrush, herpes zoster. M. TB more common
What happens if the CD4 count drops below 200?
pneumocystis carinii, cryptococcus neoformans, toxoplasma
What happens if the CD4 count drops below 50?
Mycobacterium avium-intracellulare, CMV
How does HIV cause disease?
Direct viral disease- constitutional symptoms
neuro damage- monos-macros-> inhibit neuronal groth by the HIV envelop roteins. encephalopathy- AIDDS dementia. Aseptic meningitis.
2nry disease
Malignancies- B-cell lymphoma. EBV; Kaposi's sarcoma, HHV8
Oportunistic Infections
What are some of the bacterial opportunistic infections in AIDS?
venous lines- staph
bad b-cells- encapsulated- H.flu, strep pneumo
bad cell mediated immunity- TB, MAI
What are some of the fungal opportunistic infections in AIDS?
candida albicans- very common
cryptococcus- meningitis- no traditional signs, just fever
Histoplasma capsulatum, coccidiodes- disseminated disease
Pneumocystis carinii penumonia- Most common infection. w/o prophylaxis, 15% each year.
What are some of the viral opportunistic infections in AIDS?
Herpes zoster
EBV- hair from the tongue
Herpes simplex- genital and oral outbreaks
CMV- chorioretinitis and blindness.
What are some of the protozoal opportunistic infections in AIDS?
Toxoplasmosa- mass lesions in the brain.
cryptosporidium, microsporidida, Isospora
HSV-1:
what's it cause?
how's it transmitted?
Gingivostomatitis, keratoconjunctivitis, temporal lobe encephalitis, herpes labialis
Respiratory sectresions.
HSV-2:
what's it cause?
how's it transmitted?
Herpes genitalis, neonatal herpes
Sexual contact, perinatal
VZV:
what's it cause?
how's it transmitted?
Shingles, encephalitis, pneumonia
Resp secretions
EBV:
what's it cause?
how's it transmitted?
Mono, Burkitt's
Respiratory secretions, saliva
CMV:
what's it cause?
how's it transmitted?
congenital infection, mono, pneumonia
Congenital, transfusion, sex, saliva, urine, transplant
HHV-8:
what's it cause?
how's it transmitted?
Kaposi's
Sex contact
What is the Tzanck test?
smear of open skin vesicle to detect multinucleated giant cells. Assay for HSV1,2 and VZV
Describe Gingivomatitis
HSV-1
painful swollen gums and mucous membranes with multiple vesicles. Fever and systemic.
What is herpetic keatitis?
most common cause of corneal blindness in US.
What is the role in HSV-1 in Encephalitis?
Most comon viral cause.
treatable. cell death and brain tissue swelling.
What is the death TORCH?
Toxoplasmosis
Rubella
CMV
HSV,HIV
Syphilis
What are the congenital effects of CMV?
mental retardation
microcephaly
deafness
seizure
What is reactivation CMV like?
retinitis, pneumonia, disseminated infection and death.
What is the difference between CMV infections in AIDS patients and BM transplant patients?
BM- pneumonia
AIDS- retinitis, colitis, viremia

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