Path: HIV/AIDS Flashcards
List the 3 major routes of transmission of HIV
sexual contact, parenteral inoculation, passage of the virus from infected mothers to their newborns
Is it possible to spread HIV with an insect vector?
It is virtually impossible
T/F: After needle-stick accidents, the risk of seroconversion is believed to be about 3%, and antiretroviral therapy given within 24-48 hrs of a needle stick can reduce the risk of infection 8-fold.
False. 0.3% is the rise of seroconversion
Does HIV infect naive T cells or memory and activated T cells more preferentially? Why
HIV infects memory and activated T cells more preferentially. It is inefficient at productively infecting naive T cells because the naive T cell contains an activated form of an enzyme that introduces mutation in the HIV genome, apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G (APOBEC3G). Enzyme works by trading cytosine for uracil in viral DNA transcript.
Is HIV entirely vulnerable to APOBEC3G?
Of course not! HIV is the most evil and cunning of all viral assholes. It has evolved to express a viral protein called protein Vif that binds to ABOBEC3G and promotes its degradation.
What happens to a latently infected CD4+ cell when it is activated by a pathogen or cytokines?
The activation causes NfkB to be released from IkB and be translocated to the nucleus where it will initiate transcription of not only genes for IL-2 and its receptor, but also the HIV genes. This usually results in CD4+ lysis.
Profound immune deficiency, primarily affecting cell-mediated or humoral immunity, is the hallmark of AIDS?
Cell-mediated immunity is primarily affected
What other three immune cells are also infected alongside CD4+ cells?
monocytes, macrophages, and dendritic cells. This is an important aspect of the HIV pathogenesis.
What is associated with increased rate of cellular infection and progression to AIDS?
Active viral replication. Duh.
What does the Vpr protein of HIV do?
allows nuclear targeting of the HIV preintegration complex through the nuclear pore of host cells.
How are macrophages especially important to HIV infectivity and replication?
Because they are more resistant to lysis by viral replication than CD4+ cells, they act as reservoirs of HIV. In late stages of HIV infection, when CD4+ T cell numbers decline greatly, macrophages may be an important site of continued viral replication.
How are monocytes important to HIV pathogenesis?
They may be vehicles for HIV to be transported to various parts of the body via the blood stream, including the nervous system.
How does HIV cause impaired mental function?
It travels to the CNS via monocytes where it forms granulomas. The mere presence of granulomas is not the basis of infection, rather indirectly by viral products and by soluble factors produced by infected microglia. Included among the soluble factors released: IL-1, TNF, IL-6, and nitric oxide (induced in neuronal cells by gp41). Direct damage of neurons by soluble HIV gp120 has also been postulated.
Describe the humoral and cell-mediated immune responses to HIV, post-infection.
Anti-envelope and anti-p24 antibodies (humoral) and CTLs (cell-mediated). Response is greatest @ 12 wks post-infection.
Characterize acute (early) infection by HIV as it relates to location and cell-type affected.
infection of memory CD4+ T cells expressing CCR5 in mucosal lymphoid tissues, and death of many infected cells.
Let’s play “Do You Remember from Block 1?”
Where are most of the lymphocytes found in the body?
mucosal lymphoid tissue
What are some clinical presentations of HIV mucosal infection?
damage to epithelium, defects in mucosal barrier functions, and translocation of microbes across epithelium.
How soon after infection can high numbers of HIV be detected in the blood?
Within DAYS
What immune cells are most likely responsible for the initial containment of HIV (reflected by a drop in viremia to low but detectible levels by 12 weeks after primary exposure)?
CTLs
Describe the acute retroviral syndrome of HIV.
clinical presentation of the initial spread of HIV and the host response. Occurs 3-6 weeks after infection, resolves spontaneously in 2-4 weeks. Clinically, this phase is associated with a self-limited acute illness with nonspecific symptoms, including sore throat, myalgias, fever, weight loss, and fatigue, resembling a flu-like syndrome. Rash, cervical adenopathy, diarrhea, and vomiting, may also occur.
BASICALLY, YOU HAVE THE FLU
The extent of viremia, measured as ________ ______ levels, in the blood is a useful surrogate marker of HIV disease progression.
HIV-1 RNA
What is the viral set point and how does it help predict HIV disease progression (i.e. how many yrs pt has left)?
The viral set point, a predictor of the rate of decline of CD4+ T cells, and therefore, progression of HIV disease (years-to-live prognosis), is the viral load at the end of the acute phase reflecting the equilibrium reached between the virus and the host immune response.
What is the most reliable short-term indicator of HIV disease progression?
CD4+ T cell count
Where are the locations of major HIV replication and cell destruction during the chronic phase of HIV disease? Describe the clinical manifestation during this time.
lymph nodes and spleen. Few to no clinical manifestations present.
