Micro, Ass 12

p24

Core or Capsid protein in HIV, encoded by the gag gene;

 

p24 levels are used to determine viral load by ELISA which detects antibodies to the p24 protein capsid and HIV.

gp120

HIV surface protein that mediates receptor binding;

Encoded by the env gene

gp41

HIV surface protein that mediates membrane fusion activity;

Encoded by the env gene;

 

Drug target* of Enfuvirtide, a fusion inhibitor which binds to gp41 and pervents fusion of the viral and host membranes preventing viral entry into host cells.

What gene encodes HIV reverese transcriptase, protease and integrase?
the pol gene
T/F HIV is a – sense, enveloped, ssRNA genome

FALSE

 

+ Sense*

 

Is ssRNA and is enveloped

Tat

HIV accessory protein;

 

Enhances the rate of proviral genes integrated into the host genome.

Rev

HIV accessory protein;

Facilitates transport of unspliced viral mRNAs out of the nucelus for translation in the cytoplasm

CXCR4
Chemokine receptor found on T cells (one of the possible second bindings, in addition to binding CD4+ receptors) which allows entry of viral entry into host.
CCR5

Chemokine receptor on Macrophages;

Along with CXCR4, a possible secondary binding in addition to CD4+ to allow viral entry into host cells;

 

Drug Target* of Maraviroc which binds and inhbits viral fusion with host cell membranes;

 

Mutations in CCR5 are associated with resistance to HIV infection.

T/F: Binding of CXCR4 chemokine receptor by HIV is necessary but not sufficient to allow viral entry into host cells.

True (though CCR5 can also work);

It is required that HIV bind CD4+ and one of the chemokine receptors (either CXCR4 or CCR5) in order for membrane fusion and viral entry into the host cell to take place.

T/F: During the Asymptomatic/Latent phase of HIV CD4+ T cell levels rebound to normal and are maintained because the virus has slowed replication.

FALSE;

 

During the latent phase CD4+ T cells do rebound somewhat but then begin a steady decline. Also, during this period the virus is still replicating at a high level.

What fluids are considered “high risk” for HIV transmission?

Blood, semen, cervical secretions, and breast milk;

 

 

CSF, urine, saliva and tears are low risk.

What HLA type is associated with a status of being an Elite controller?
Elite controllers are long-term non-progressors who are more likely to be HLA-B57.
T/F: HIV integration does not require host cell division.
TRUE
What mutations are associated with being a long-term survivor?
Nef deletion (accessory protein);
What are the 4 chief drug targets in in HIV treatment?

Fusion,

Reverse Transcription (NRTI and NNRTIs),

Integration,

Proteases (maturity)

Atripla

The first combination, once a day AIDs treatment;

 

3 drug combo of efavirenz, emtricitabine and tenofovir.

T/F: When resistance arises to a drug in an AIDS pt’s HAART regimen, it is best to change every drug they are on and not just the one they became resistant to.
TRUE, better to change all drugs and not just one.
What agents cause superficial fungal infections and what are the symptoms and treatments for such infections ?

Causitive agents: Malassezia Furfur (tinea versicolor), Exophiala werneckii (tinea nigra), blac and white piedra;

;

Sx: do not cause inflammation!
Piedra infx cause development of nodules of asci on hair shafts.

Piedra and tinea cause hyper and hypopigmented spots on the skin.

Infants and the IC can develop fungemia;

;

Tx: Selenium sulfide (topical dandruff shampoo), shaving effected area, topical azoles.

What fungal agents have a “Spaghetti and Meatballs” appearence on KOH mount?

Superficial fungal infections

;

Tinea versicolor, tinea nigra, black and white piedra.

What fungi can be visualized under Woods Lamp and what is their appearance?

Superficial fungal infections

;

Tinea versicolor, tinea nigra, black and white piedra.

;

Show a Coppery Orange Fluorescence

What is the agent of Tiena infections of the skin and hair?
Microsporum
What is the chief symptom of a microsporum infection?
Puritis (cutaneous fungal infection)
What do Trichophytan and Epidermophyton cause?
Cutaneous fungal infections effecting the skin, hair, and nails.
What is the treatment for cutaneous fungal infections?

Topical azole antifungals (topical imidazoles);

;

Tx tinea capitis (scalp) with Griseofulvin (which inhbitis the mitotic spindle);

;

Treatment of these is required for weeks to months as relapses are common.

T/F: Fungal infections passed from person to person show more inflammation than those passed form animal to person.

FALSE;

Animal to person = more inflammation;

Person to person = less inflammation.

What fungus exibits “rosette-shaped conidia”?

Sporothrix schenckii – Agent of subcutaneous fungal infection known as Sporotrichosis or “rose gardeners disease” (aslo seen in handlers of sphagnum moss and in ulcerous lesions of cats);

Pulmonary form seen in alcoholics;

;

Cigar-shaped yeast in sputum or lesions.

How would you treat Sporotrichosis?

Subcutaneous fungal infection caused by sporothrix schenckii (dimorphic fungus);

;

Tx with Itraconazole or Amphotericin B + Potassium Iodide

What does it mean to say that a fungus is “dimorphic”?

They assume 2 different morphologies based on their location;

;

“Mold in the Cold, Yeast in the Beast”

;

Cutaneous fungal infections are monomorphic as they only assume the mold form.

What are the symptoms, agents, and treatment of systemic fungal infections?

Sx: Acute pulmonary infections (“Fungus Flu”) that do not respond to antibiotics and can progress to chronic pulmonary issues or dissiminate;

;

Etiologic agents: Histoplasma, Coccidioides, Blastomyces, and Cryptococcus;

;

Treatment: is typically with Amphotericin B which punches a hole in the cell membrane,

Ketoconazole is also often used and Flucytosine is used in cryptococcal infections.

What fungal infection(s) can be confused with TB?
Histoplasmosis (calcified lesions in the lung) and Aspergillus (fungus ball in the lung).
What two key things are helpful in the diagnosis of histoplasmosis?
In sputum cytology and blood culture (remember it is in macrophages) seeing macrophages with yeast inside + Tuberculate Macroconidia
What diseases is called “spelunkers” or “chicken farmers” disease?

Histoplasmosis;

;

Found in soil/dirt/dust enriched with bat and bird droppings;

;

Is an intracellular yeast that resides within macrophages.

What fungus has an environmental (arthrocondia) form that is inhaled and forms a spherule inside the body?
Coccidioides, the etiolgical agent of “Desert Valley Fever”
What fungus causes “Desert Valley Fever”?
Coccidioides
How do you make a diagnosis of Coccidioides?
See spherules with endospores
What fungus can disseminate in the third trimester of pregnancy or in IC pt?
Coccidioides
Where are infections of Coccidioides commonly seen?
The Southwestern United States
For which fungus is visualization of “Broad based budding blastomyces” diagnostic?
Blastomyces dermatidis
What is the agent of Dermatitidis?
Blastomyces dermatidis, infection disseminates to the skin and to mucocutatneous areas.
What fungi are endemic to the Ohio and Mississippi River Valley areas?
Histoplasmosis and Blastomyces dermatidis
What fungus is transmitted through pigeon droppings?
Cryptococcus neoformans
What is the microscopic appearence of Cryptococcus neoformans?

It is a monomorphic, heavily encapsulated yeast that can be cultured from the CSF and visualized using India Ink;

;

Note that india ink is insensitive and latex agglutination should be used to confirm as well as culture as Cryptococcus is a Urease Positive Yeast.

What fungus has the appearence of having a “halo” around it when cultured?
Cryptococcus neoformans
What is a common agent of meningitis in AIDS patients?
Cryptococcus neoformans

What are the opportunistic fungi that are a concern for IC pts?

Which is the leading cause of death in AIDS pts?

Aspergillus, Candida, Zygomycoses, and Pneumocystis jioveci;

;

Pneumocystis jioveci is a leading cause of death in AIDS patients.

What fungus can be described as an acute-angled fungus with septate hyphae?

Aspergillus Fumigatus;

Is also monomorphic (always in its fungal form);

;

A is for Asperigullus, Acute angles, and Amphotericin (used to tx aspergillus)

What are risk factors for Aspergillus infection?
IC status, prior use of steroids or transplants.
Infection with which fungus can lead to the development of a “fungus ball” visualized on CXR?
Aspergillus
What can invasive aspergillosis in a severely IC pt cause?

Nasal Congestion,

Meningitis,

MI and many other manifestations

How can Candida be cultured?

On Sabouraud’s agar – contains peptones and dextrose at pH 5.6;

 

Candida forms germ tubes if incubated @ 37 degrees in serum.

Who is at risk for Cutaneous candida infections?

The IC, diabetics, obese pt, pregnant pt, IV drug users;

 

Infection occurs where skin touches skin and can lead to gastritis, sepsis and endocarditis (esp in the IC and IV Drug users)

Who is at risk for Chronic Mucocutaneous Candidiasis (CMC)?

Immunocomprimised patients and

Pt with DiGeorge’s Syndrome

How is Candidiasis treated?

Nystatin (topical or oral polyene antifungal);

;

Nystatin + Amphotericin B for dissiminated infx;

;

Flucytosine (which inhibits DNA synth) and capsofugin could be used.

What are the Zygomycoses?

What do they look like and what do they cause?

Zygomycoses are opportunistic fungi = Mucor, Rhizopus, Absidia;

;

Non-septate hyphae typically at 90 degree angles

;

Cause severe infections that lead to tissue necrosis and attacking of the brain (rhinocerebral form of mucor can be fatal, man without a face story).

What type of fungal infection are ketoacidotic patients prone to? What other group of pt are at risk for this infx?

Zygomycoses

;

Pt with leukemia are also succeptible to this infection.

;

Tx: Amphotericin and removal of all necrotic tissue.

What fungus has a “dented helmet/condom/soccer ball” appearence?
Pneumocystis jiroveci
PCP Pneumonia

Caused by Pneumocystis jiroveci infection (PneumoCystis Pneumonia, PCP);

Fever, shortness of breath, non-productive cough;

;

H;E stain of lung tissue shows honeycomb appearence, patchy infultrates on CXR;

;

Dx: silver-stained cysts on BAL;

;

Tx: Trimethoprim (inhibits DHFR)

How do you treat a pneumocystis infx?
Trimethoprim* (inhibits DHFR)

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