5.8 AIDS Flashcards
AIDS
a retroviral disease resulting in profound immunosuppression leading ot opportunistic infections, secondary neoplasms, and neurologic manifestations
AIDS Epidemiology
900,000 cases in US and 60 million world wide, homosexual and bisexual males 57%, IV drug users 25%, Heterosexuals: 10% (includes many I.V. drug users) Recipients of blood components: 2% (includes 0.8% hemophilliacs), Unknown: 6%
What is the most common method of spread in the US
receptive anal intercourse btw male homosexuals
Spread in the US btw males and females
male to female spread is 20X more efficient than female to male, Mother to child spread in 2% of cases
Spread due to blood products
virtually eliminate, AIDS is a wimpy virus and needs a host cell. Can just survive on a needle. Little risk in heathcare workers
What is the major connection to heterosexual transmission and aids
IV drug use is a major connection to heterosexual transmission and growing incidnece in women and mother
Age groups affected
number 1 cause of death in men btw 25 and 44, 3rd leading cause in women in the same age group
Etiology of AIDS
human immunodeficiency virus, HIV1 and HIV2, retrovirus, Target CD4 lymphocytes and macrophages
Why is infection of Macrophages by HIV a problem
bc the MACs are the reservoir we cant clear. With triple drug therapy we can take pts to the point where we cannot find any viral strains with pcr but if you take them off it will come back. We think it_s the Mac’s acting as the reservoir that we can’t target well
HIV
replication achieved like other retroviruses, requires cellular activation bc the viruse uses host mechanisms
What does HIV use to get in
CD4 and CCR5 on the T cell and gp120 on the virus
How does the virus trick the cell to make its proteins
CD4 cells make IL2 under a promoter that NFkB binds to. Viral DNA has a smilar promotor that NFkB can bind to as wells. So when the T cells are stimulated to divide and secrete IL2, they are also induced to synthesize the viral proteins.
tat gene
enhances transcription of viral genes 1000 fold
rev gene
enhances transport of mRNA
nef gene
necessary for progressive infection. Down regulates MHCI, upregulates FasL
Pathogenesis of AIDS via the immune system
high tropism for CD4 t-cells, viral gp120 has high affinity for CD4 molecule. Also binds with CCR5 or CXCR4, gp41 then induces fusion and entry, a very low percentage of CD4 cells contain the virus, 2 billion CD4 cells die each day, thus a battel royal is goin on with the body rapidly eliminating the infected cells during the “latency” period, finally the body can’t replenish and CD4 count drops resulting in imparied immunity and increased infections
Cytopathic effects of HIV
killing of infected cells by CD8 killer cells, coating of non-infected cells with soluble gp120 and killing of non-infected cells by CD8 cells, preferential kill of memory CD4 cells (they have higher levels of CCR5), supression of non-infected CD4 cells
Macrophages/Monocytes in HIV
infection of these cells important in pathogenesis of AIDS, there are M-tropic and T-tropic forms of virus based on affinity for CCR5 (both T and macs) and CXRC4 (on T cells), most initial infections are M-tropic. T-tropic develops later in disease. Macrophages are resistant to cytopathic effects of virus so they become reservoirs of virus.
DC and HIV
Dendritic cells also infected an may be first cell to see the virus bc of their anatomic location and fn.
Macrophages role in HIV
Macrophages are probably responsible for transmitting to CNS. HIV does not infect nurons but the microglial cells that are infected cause a cytokine storm that degenerates the neurons.
What do you see in alveolar spaces of HIV pts
frothy edema – pnemocystis pnemonia infections
HIV CNS manifestations
frequently presenting symptoms, neurons not infected, macrophages/microglia contain virus, neuronal death probably induced by toxic products secreted by infected microglia
HIV and secondary Neoplasms
Kaposi’s Sarcoma, Non-hodgkin lymphoma (EBV), Cervical carcinoma (HPV)
HIV secondayr infection in the lungs
CMV, you’ll see huge cells with cowdry type 1 inclusions. CMV could be living in leukocytes and you only see it when you are severly immuno compromised.
Kaposi’s Sarcoma
rare in non-AIDS pts, primitive vascular cells, neoplasm Vs reactive hyperplasia, rates much higher in homosexual men, with AIDS than other groups with AIDS. Rate also higher in women who contracted AIDS from sex with bisexual men than with IV drug users.
Non-Hodgkin Lymphoma
Most are aggressive B-cell lymphomas, systemic, CNS, body cavity, Long term polyclonal B-cell activation and EBV involved
Cervical carcinoma
related to very high incidence of paplloma virus in AIDS pts
