5.8 AIDS

Question 1

AIDS

Answer 1

a retroviral disease resulting in profound immunosuppression leading ot opportunistic infections, secondary neoplasms, and neurologic manifestations

Question 2

AIDS Epidemiology

Answer 2

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%

Question 3

What is the most common method of spread in the US

Answer 3

receptive anal intercourse btw male homosexuals

Question 4

Spread in the US btw males and females

Answer 4

male to female spread is 20X more efficient than female to male, Mother to child spread in 2% of cases

Question 5

Spread due to blood products

Answer 5

virtually eliminate, AIDS is a wimpy virus and needs a host cell. Can just survive on a needle. Little risk in heathcare workers

Question 6

What is the major connection to heterosexual transmission and aids

Answer 6

IV drug use is a major connection to heterosexual transmission and growing incidnece in women and mother

Question 7

Age groups affected

Answer 7

number 1 cause of death in men btw 25 and 44, 3rd leading cause in women in the same age group

Question 8

Etiology of AIDS

Answer 8

human immunodeficiency virus, HIV1 and HIV2, retrovirus, Target CD4 lymphocytes and macrophages

Question 9

Why is infection of Macrophages by HIV a problem

Answer 9

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

Question 10

HIV

Answer 10

replication achieved like other retroviruses, requires cellular activation bc the viruse uses host mechanisms

Question 11

What does HIV use to get in

Answer 11

CD4 and CCR5 on the T cell and gp120 on the virus

Question 12

How does the virus trick the cell to make its proteins

Answer 12

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.

Question 13

tat gene

Answer 13

enhances transcription of viral genes 1000 fold

Question 14

rev gene

Answer 14

enhances transport of mRNA

Question 15

nef gene

Answer 15

necessary for progressive infection. Down regulates MHCI, upregulates FasL

Question 16

Pathogenesis of AIDS via the immune system

Answer 16

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

Question 17

Cytopathic effects of HIV

Answer 17

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

Question 18

Macrophages/Monocytes in HIV

Answer 18

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.

Question 19

DC and HIV

Answer 19

Dendritic cells also infected an may be first cell to see the virus bc of their anatomic location and fn.

Question 20

Macrophages role in HIV

Answer 20

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.

Question 21

What do you see in alveolar spaces of HIV pts

Answer 21

frothy edema – pnemocystis pnemonia infections

Question 22

HIV CNS manifestations

Answer 22

frequently presenting symptoms, neurons not infected, macrophages/microglia contain virus, neuronal death probably induced by toxic products secreted by infected microglia

Question 23

HIV and secondary Neoplasms

Answer 23

Kaposi’s Sarcoma, Non-hodgkin lymphoma (EBV), Cervical carcinoma (HPV)

Question 24

HIV secondayr infection in the lungs

Answer 24

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.

Question 25

Kaposi’s Sarcoma

Answer 25

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.

Question 26

Non-Hodgkin Lymphoma

Answer 26

Most are aggressive B-cell lymphomas, systemic, CNS, body cavity, Long term polyclonal B-cell activation and EBV involved

Question 27

Cervical carcinoma

Answer 27

related to very high incidence of paplloma virus in AIDS pts