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Mercy CLS 1: Immunology > HIV > Flashcards

HIV Flashcards

1
Q

HIV modes of transmission.

A
  • Directly by bloodstream
  • Through abraded mucosa (sexual)
  • Through genital secretions (semen)
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2
Q

Which cells does HIV infect? Where?

A

CD4+ cells (Th cells)
Monocytes and macrophages

Virions migrate to lymph nodes and infect local CD4+ cells, as well as those circulating through. Eventually these (and the virus) reach the bloodstream.

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3
Q

3 stages of HIV and time frames for each.

A
  1. Burst of viral replication. 2-6 weeks after infection. Sx last 2-4 weeks.
  2. Asymptomatic period. Steady-state level of virus reached after 6-9 months. May last years.
  3. AIDS. Average time between infection and AIDS is 10-11 years.
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4
Q

Symptoms of 3 stages of HIV.

A
  1. Fever, sore throat, malaise, rash, lymphadenopathy, h/a, myalgia.
  2. No symptoms in asymptomatic period.
  3. Various opportunistic infections in AIDS period. 90% cases result in death.
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5
Q

List common opportunistic infections/diseases that HIV patients are subject to.

A
  • Pneumocystis carinii
  • Cytomegalovirus (CMV)
  • Cryptococcus
  • Mycobacteria
  • Toxoplasma
  • Kaposi sarcoma
  • Chronic lymphadenopathy
  • Rare lymphomas
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6
Q

Describe the mechanism by which HIV replicated in Th cells, including enzymes.

A

HIV attaches using gp120 to CD4 (CXCR4 also necessary). Viral envelope fuses and 2 RNA strands enter host. Reverse transcriptase transcribes RNA to ssDNA. RNAse H destroys viral RNA. Polymerase makes dsDNA, which integrase inserts into host genome. Activation of host cell causes viral DNA to transcribe into viral RNA and synthesize new viral particles.

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7
Q

Describe 2 ways macrophages/monocytes can be infected by HIV.

A
  1. Engulfment of free HIV or HIV attached to Ab.
  2. Attachment of gp120 to CD4.
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8
Q

List 3 ways cell death can occur during HIV.

A
  1. Complement activation causes lysis. Due to Ab to gp120 and gp41 on infected cell.
  2. ADCC—Ab dependent cell mediated cytotoxicity. Monocytes/macrophages attach to Fc of Ab on infected cells.
  3. Cytotoxic T-cells are directed to viral proteins on surface of infected cell.
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9
Q

How can CD4+ depletion occur during HIV…even noninfected cells?

A

Possible reasons:

  • HIV may kill/infect/impair cells that are necessary for growth of CD4+ lymphocytes.
  • HIV may induce cells to secrete substances that are toxic to CD4+ lymphocytes.
  • gp120 on surface of infected cells may react with CD4, leading to fusion and giant multinucleated cells that die.
  • Free gp120 binds to CD4 leading to production of Ab against these cells (autoimmunity).
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10
Q

How does HIV infection impair the function of CD4+ cells?

A
  • gp120 binding to CD4 prevents the interaction of the T-cell with MHCII.
  • infected cells cannot express CD4, and do not produce as much IL-2, which activates cytotoxic T-cells.
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11
Q

How are the cytopathic effects of HIV on monocytes/macrophages different from those on Th cells?

A

Cytopathic effect is much less significant for monos/macros because they have less CD4. They may act as a reservoir for HIV, transporting it throughout the body.

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12
Q

List screening, confirmatory, and monitoring tests used for HIV. (8 total)

A

Screening:
- Rapid HIV-1/2 Ag/Ab Combo (Alere)
- HIV-1/2 Ag/Ab Combo immunoassay

Confirmatory:
- HIV-1 Western blot
- HIV-1/2 Ab differentiation immunoassay
- HIV-RNA Qualitative test

Monitoring:
- HIV-RNA Quantitative test (Viral load testing)
- HIV genotyping
- CD4 counts and CD4:CD8 ratio

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13
Q

What are the specimen requirements for an HIV-RNA test?

A

Best to keep sample completely sterile (ie don’t use it for another test before hand).

EDTA and ACD whole blood must be frozen and plasma removed within 6 hours of collection to prevent degradation of RNA by native RNases in plasma.

Different assays of HIV-RNA quantitation will yield different results, so the kit used should be consistent.

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14
Q

What does the CD4:CD8 ratio tell use about the course of HIV infection?
What is a normal ratio?

A

Normal is greater than 1.

The ratio tells us about the progression of AIDS. Low ratio is a late manifestation of AIDS.

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15
Q

What is the goal of antiretroviral therapy in HIV patients?

A

Complete, maximal, sustained, uninterrupted inhibition of virus replication, resulting in the decrease of HIV-RNA levels and increase of CD4+ cell count.

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16
Q

Describe the action of antiretroviral drugs.

A

Inhibit either reverse transcriptase or the proteases necessary for viral replication.

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17
Q

Which test is most useful in monitoring the effectiveness of antiretroviral drugs?

A

Viral load (HIV-RNA quantitative)

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18
Q

What does HAART stand for and what effect should it have on an HIV patient?

A

Highly Active AntiRetroviral Therapy

Should result in substantial decline in viral load by 4-8 weeks, and lead to viral loads < 500 copies/mL in 12-16 weeks.

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19
Q

Risks/limitations of antiretroviral therapy for HIV.

A
  • Side effects
  • Duration of effectiveness unknown
  • Replication of virus not completely stopped
  • Therapy cannot be withdrawn
  • Eventual breakthrough of resistant virus seems inevitable
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20
Q

HIV discovered when?

A

1981

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21
Q

2 HIV strains have about —% homology

A

50%

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22
Q

HIV DNA intermediate is integrated into host cell genome as a(n) ——-

A

provirus

23
Q

Seroconversion occurs when in HIV infection?

A

First stage (2-6 weeks)

24
Q

About —-% of AIDS patients develop CNS & PNS disease

A

35%

25
Q

RNA –> DNA

A

reverse transcriptase

26
Q

HIV cytopathicity highest in cells with…

A

highest CD4 density

27
Q

Explain the T-cell event that leads from the latent period to AIDS

A

Mitogens or antigens stimulate T-cells, leading to their activation, resulting in cytokine production and extensive viral replication.

28
Q

During HIV’s latent period, viral load (stays steady/increases/decreases) and CD4 count (stays steady/increases/decreases).

A

viral load stays steady
CD4 count decreases (gradually)

29
Q

1st and 2nd generation HIV testing detected —— and took —— days to be detectable

A

HIV-1 Ab only
42-60 days

30
Q

3rd generation HIV testing detected ——- and took —— days to be detectable

A

HIV-1/2 Ab
21-24 days

31
Q

4th generation HIV testing detects ——- and takes ——- days to be detectable

A

HIV-1/2 Ab and p24 Ag
14-15 days

32
Q

earliest routine marker for HIV detection

A

p24

33
Q

p24 is positive within —– weeks of exposure

A

2-3

34
Q

p24 detection is problematic in which pop?

A

children < 1 month

35
Q

p24 marker disappears once…

A

Ab is present. Reappears in AIDS.

36
Q

HIV-1/2 Ab appears within what time after exposure? Average?

A

6 weeks to 6 months. Average is 2 months.

37
Q

2 main methods of HIV-1/2 Ag/Ab combo assay

A

CLIA
ELISA

38
Q

When is the rapid HIV combo test done now?

A

Employee exposure incidents.
Pregnant women with unknown HIV status at time of delivery.

39
Q

3 types of HIV viral proteins detected by Western blot

A

GAG (group specific antigen)
POL (polymerase)
ENV (envelope)

40
Q

Explain HIV Western blot results.

A

At least 2 major bands is considered positive.
Only 1 major band is considered indeterminate. Repeat in duplicate.
No bands must be present to be considered negative.

41
Q

Faster, fewer indeterminates, and less expensive than Western blot for HIV.

A

HIV-1/2 Ab differentiation immunoassay.

42
Q

HIV-RNA detects RNA —- days after infection

A

10-12

43
Q

FDA approved methods for HIV-RNA

A

PCR
TMA (transcription-mediated amplification)

44
Q

CDC recommends which step if a patient tests negative for HIV-1 and HIV-2 on the Ab differentiation test?

A

HIV NAT test

45
Q

Minimum “goal” CD4 cell count

A

500 cells/nL^3

46
Q

HIV-RNA quantitative tests detect down to —- copies/mL

A

20

47
Q

Valuable prognostic indicator for HIV during latent phase.

A

Viral load.
< 5000 copies/mL indicates low rate of progression.
> 50,000 copies/mL indicates high rate of progression.

48
Q

Test that would be done if HIV viral load suddenly increases during treatment.

A

Genotyping

49
Q

Genotyping has limited usefulness when patient’s HIV levels are less than —–

A

1000 copies/mL

50
Q

CD4 count indicating AIDS

A

< 400 cells/nL^3

51
Q

CD4 count indicating great risk for opp. infection

A

< 250 cells/nL^3

52
Q

CD4 count indicating great risk for P. carinii

A

< 200 cells/nL^3

53
Q

HIV can get stuck on the surfaces of —— cells

A

dendritic

54
Q

Viral load monitoring for AIDS patients happens every —- months

A

3-4

Mercy CLS 1: Immunology (19 decks)

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