BLD434 Section 5 Flashcards
AIDS
Acquired Immune Deficiency Syndrome
- AIDS due to HIV is a secondary infection
gp41 and gp120
Glycoproteins on virion that form spike protein that bind to CD4 on target cell membranes. gp41 = stem; gp120 = bulb
Macrophage-tropic HIV strain
Comes first
Generally initiated at mucosal sites of entry by binding co-receptor CCR5 and preferentially infect macrophages and DCs
Lymphocyte-tropic HIV strain
Binds CXCR4 and infects CD4+ T cells
Progresses, leads to AIDS
Reverse transcriptase
Copies RNA into cDNA after HIV injects the host cell with its RNA genome
Integrase
Splices HIV cDNA into the host cell genome and it just sits there - Quiescence provirus (latent)
Allows for a permanent stable infection of a host cell because while the person is always HIV+ they aren’t always having symptoms.
Acute HIV Syndrome
Phase occurs 4-8 weeks after initial exposure to HIV. Person will be highly contagious and will only sometimes develop flu-like symptoms.
Why do CD4+ T cell numbers plummet during end of acute infection stage of HIV, and then partially rebound?
They get killed by CD8+ Tc. They rebound due to new production of naive CD4+ T cells in the thymus.
Combination Antiviral Therapy (ART) vs single drug therapy for HIV
ART is used to destroy entire populations of viruses before they accumulate enough to mutate to resist all the drugs.
What characteristics of HIV make it difficult to create an effective vaccine against HIV?
- High mutation rate of HIV genome
- Must target both CD8+ T cell response and mucosal Ab response to be effective
- HIV remains latent as provirus integrates into host genome and can reactivate later
Serology
The study of non-cellular components in blood`
EIA
Enzyme Immunoassay
- Plastic wellss w fixed Ab or Ag to detectt Ag-Ab reactions. Produces a colored product
Window period or eclipse
The time between exposure and presence of detectable serum Ab
- False negatives can occur here
Sensitivity
Measures the percentage of real positives that are identified as positive results.
Specificity
The percent of negatives that are correctly identified as negatives.
What are the 2 main analytes that can be measured in serological tests for infectious disease?
Patient Ab & viral Ag
Testing Algorithm for HIV
- Screening: HIV-1/2 Ag/Ab combination immunoassay
- Confirmatory: (if screen +) HIV-1/2 Ab differentiation immunoassay
- Can detect 1, 2, or both, or be negative for both (go to 3) - Discrepant results test: HIV-1 NAT (b/c most popular in US)
*High risk adult would get immediate viral Ag nucleic acid testing
What are the drawbacks of early detection EIA tests for HIV diagnosis? How has 4th gen EIA limited these?
Large window period (45 days) giving false negatives. Also, false positives due to human cell contaminants. And cannot detect HIV-2
4th gen has shorter window period (14 days) and can detect both HIV-1, HIV-2, and p24. Still has some false positives tho.
Confirmatory tests for HIV
Western Blot & NAT (nucleic acid test)
What is the preferred method for detecting HIV in newborn infants? Why does this differ from the usual?
Test for viral nucleic acid via qualitative PCR, for either
1. HIV cDNA in mononuclear cells
2. HIV virion RNA in plasma
Adult screening can’t be used because passive IgG from mom in baby’s serum can cause false positives for up to 18 months old. Also, baby’s IgM to HIV lacks specificity; not adequate for testing.
HIV viral load
Measures the amount of HIV viral RNA in the patient blood sample.
Increase = drug resistance
Decrease = successful drug therapy
What laboratory test monitors progression from HIV to AIDS?
CD4+ T cell count (flow cytometry)
Test can read 3 things to be indicative of AIDS; only need 1:
1. Absolute T cell count <200/micro
2. CD4 T cell % (of total lymphocytes, <14%)
3. CD4:CD8 ratio (<1:1, reference is 2:1)
Fecal-oral route
Transmission via contaminated food/water (ex: HAV, HEV)
Parenteral route
Transmission via blood/body fluids (ex: HBV, HCV, HDV)
IgM Ab in viral staging
Presence indicates current or recent
- In a newborn, this indicates congenital infection (from mother)
IgG Ab in viral staging
Presence indicates current or past infection & immunity to re-infection
Viral Ag or Viral DNA or RNA in viral staging
Positive serological tests indicate current infection
Assays in patient serum for acute hepatitis panel
Hep A = IgM anti-HAV
Hep B = IgM anti-HBV and HBsAg
Hep C =
