BLD 434 - Quiz 5 Flashcards
Define the abbreviation AIDS and identify whether AIDS due to HIV infection is a primary or secondary immunodeficiency.
Acquired immune deficiency syndrome - it is a secondary immunodeficiency.
Identify whether HIV-1 or HIV-2 is more common in the U.S.
HIV-1
State whether the number of people infected with HIV worldwide has leveled off, declined, or is still increasing.
Worldwide the number of people living with HIV has stabilized/ leveled off
Identify the function of gp120 and gp41 in the interaction with host cell membranes and eventual infection of host cells.
It is the docking protein of HIV that binds directly to CD4 on target cell membranes into infecting them
Explain the difference between macrophage-tropic and lymphocyte-tropic HIV strains, and how they can change over time during HIV infection of an individual.
Macrophage-Tropic: HIV strains generally initiate infection at mucosal sites of entry by binding to CCR5 (HIV binds to CD4 and chemokine receptor CCR5 in mucosal sites), and preferentially infect macrophage and dendritic cells (as well as CD4+ T cells to a lesser degree (not as effective). Mucosal sites are where you are going to have macrophages constitutively present within the connective tissues. Most HIV infections that are passed by sexual contact, either homosexual or heterosexual contact, are called macrophage-tropic HIV strains.
Lymphocyte-Tropic: about halfway through an HIV infection in an individual, the strain mutate into another form, the lymphocyte-tropic form. HIV strains preferentially bind to CXCR4 (chemokine receptor) and preferentially infect CD4+ T lymphocytes (later in infection; hasten progression to AIDS). Very avidly attaches and replicates in CD4+ T Lymphocytes
Explain the function and importance of “reverse transcriptase” and “integrase” HIV enzymes in creating a permanent stable infection of a host cell.
Reverse transcriptase: copies viral RNA genome into double stranded cDNA.
Integrase: - an enzyme produced by a retrovirus that enables its genetic material to be integrated into the DNA of the infected cell.
- Gives viral RNA the chance to be copied by host machinery.
Explain when the Acute HIV Syndrome occurs following exposure to HIV and identify the symptoms of this syndrome. Is the infected individual infectious to others during acute HIV Syndrome? Do all patients develop these symptoms?
Initial infection (4-8 wks) has extremely high infectious where the patient may have flu-like symptoms and is highly infectious but they don’t know they’ve been exposed.
Explain why CD4+ T cell numbers temporarily plummet during the end of the acute infection stage of HIV, and then rebound at least partially.
CD4 cells will plummet temporarily due to being attacked by the initial HIV infection. CD4 cells will increase to a new set point when immune system kicks in (another good prognostic indicator of long term health).
Explain why combination antiretroviral therapy (ART) is used in fighting HIV infection instead of single drug therapy.
Combination therapy for HIV infection, in which several antiviral drugs are used together to try and avoid the rapid generation of drug-resistant mutant viruses that occurs when one of the drugs is used alone.
List the characteristics of HIV that make it very difficult to create an effective vaccine against HIV. (Your textbook only lists one. Think.)
- HIV has a very high mutation rate because reverse transcriptase lacks proof-reading and antigens are always changing within an individual
- Must target BOTH CD8 T cell response and mucosal antibody response to be effective
- HIV remains latent until activated by a provirus
Serology
· Serology: study of the non-cellular components in the blood (i.e soluble molecules, usually proteins in the blood stream)
EIA
enzyme immunoassay (general type of test, adaptable to many antigens)
Window Period/Eclipse
the time between exposure resulting in infection and the presence of detectable serum antibody; antibody test is negative but infectious agent is transmissible during the window period
False Negative
supposed to be positive but test negative
False Positive
supposed to be negative but test positive
Identify the two main analytes that can be measured in serological tests for infectious disease.
Patient antibody and viral antigen
Explain the basics of E IA testing for detection of either patient antibody or antigen in patient serum. (Note: this must be set up differently if detecting patient antibody versus when detecting pathogen antigen in the patient sample)
- Each well pre-coated with solid-Ag (HIV viral antigens).
- Add a diluted sample of patient Ab (diluted serum).
- Allowed to react.
- If Ab that can recognize the disease is in the patient serum, it will immobilize to the Ag.
- Wash away excess serum, add Ab with an enzyme bound to it (covalently conjugated).
- Antiglobulin b/c conjugate has the ability to bind to constant domain of human Ab.
- After incubation, conjugate washed away and colorless substrate added to the well.
- If colored, positive for Ab for the disease.
- If no color, negative for Ab for the disease.
List the drawbacks of the early generation EIA tests for HIV diagnosis, and how the “fourth generation” EIA test has limited these.
First generation problems: large window period of 45 days where someone could be infected but test negative b/c the test wasn’t sensitive enough, false positives due to human cell contaminants, could not detect HIV-2 infections.
Fourth generation has a decreased window period of 14 days where there are false negatives, can detect both HIV-1 and HIV-2. Still has problems with false positives. In this generation, you can also detect p24 antigen. Sensitivity increases.
Identify the confirmatory tests available for HIV diagnosis in adults (assuming the screening test is positive).
Antibody differentiation immunoassay
NAT - nucleic acid testing
Western Blot
Identify the preferred methodology for detecting HIV infections in newborn infants, and why the usual screening test for HIV cannot be used to diagnose HIV infections in infants
The best method is to test for viral nucleic acid (cDNA) when the baby is less than one month old (x2). PCR ee5 for HIV cDNA provirus in mononuclear cells.
- qualitative PCR for HIV cDNA provirus in baby’s mononuclear cells
- qualitative PCR for HIV virion RNA in baby’s plasma
Do this at 1 and 2 mos of age.
Can’t use standard screening methods b/c of passive IgG Ab from the mother could result in false positive test up to 18 mos of age.
Baby’s IgM Ab to HIV lacks specificity and isn’t adequate for testing.
Correlate an increase or decrease in HIV viral load to the success of drug therapy in the patient. Identify specifically what “HIV viral load” is measuring and the patient sample used.
An increase in viral load means drug resistance. A decrease in viral load means successful drug therapy. HIV viral load is measuring the amount of HIV viral RNA in the patient. Use blood for the sample
Successful therapy = decreased load
Resistance = increased load
Hepatitis
inflammation of the liver
Fecal-oral route
contaminated food/water leading to Hepatitis A and E
Blood/body fluids
Mode of infection of B, C, D
Parenteral
other than the intestine - leads to Hepatitis B, C, D
HBcAg
Important viral antigen/hepatitis B core antigen. A protein that surrounds viral DNA in the virus core. Is not detectable in the serum
HBeAg
Hepatitis Be antigen. Protein is also surrounding viral DNA in the virus core similar to HBcAg. Appears shortly after the HBsAg and indicates high viral replication and a high degree of infectivity
HBsAg
Hepatitis B surface antigen- a protein in outer virus envelope and in particles in blood. First HBV antigen to appear in serum (detectable between 2 to 12 weeks after exposure), and peaks during acute infection. Persistent HBsAg is an indication of chronic or active infection
