Jack loved his job with EMS; he got great satisfaction from helping trauma victims
survive and recover. One night his unit was called to a location where shots
had been fired; they found a young man bleeding profusely from a chest wound.
After stabilizing the patient and transporting him to the hospital, Jack discovered
a nick in his gloves and a small puncture wound in his finger. As he finished
cleaning the puncture, his unit was called out to a massive rollover accident
on the interstate. By the time Jack dropped into bed the next morning, he had
completely forgotten the puncture wound.
Three weeks later, Jack thought he was coming down with the flu; he felt tired and achy, but recovered quickly. Six months later at his annual physical, Jack was routinely tested for Human Immunodeficiency Virus (HIV). The ELISA test for antibodies to HIV was positive, and a follow-up Western blot showed he had antibodies to HIV gp120, gp41, and p24.
Jack's physician ordered a PCR test to determine viral load and flow cytometry to measure Jack's numbers of circulating CD4+ cells. The viral load was background level, and the CD4+ count was normal at 980 cells/microliter. Jack felt well and had no symptoms, and his physician elected to monitor his progress and delay treatment until virus levels increased.
HIV is an enveloped retrovirus. Viral gp120 binds host cell CD4, allowing the virus envelope to fuse with the host cell membrane and viral entry into the cell. HIV has a diploid RNA genome that must be transcribed into DNA inside the host cell and integrated into the host cell DNA for the virus to replicate. It does not replicate well in resting cells, but when a T cell containing HIV is activated by antigen to divide, HIV replication increases.
HIV infection causes the body to produce specific antibodies against the virus,
which can be detected by serological tests. The
ELISA (Enzyme-Linked ImmunoSorbent Assay) that tests the patient's serum
for antibodies against HIV antigens sometimes give false positive readings. The
lab confirms the diagnosis using a Western
blot that detects antibody binding to specific HIV proteins. People infected
with HIV become symptomatic when enough of their helper T cells (CD4+ cells)
are killed that they suffer opportunistic infections. CD4+ T cell depletion often
takes years, and since Jack's levels are normal he is still asymptomatic. A low
circulating viral load is a sign that the body is still sequestering the infected
CD4+ cells in the lymph nodes, and offers a hopeful prognosis for slow disease
progression.
1. Most people infected with HIV go through an extended period of clinical latency, during which time they have no disease symptoms. This is not a true viral latency as seen in Herpes Simplex infections when viruses are not replicating. HIV is continuously replicating during clinical latency. Describe what is happening in Jack's body to suppress signs of HIV infection.
2. People with HIV develop symptoms (Acquired Immune Deficiency Syndrome = AIDS) once their CD4 T cell numbers fall below ~ 200/microliter of blood. Describe at least three ways that CD4 T cells are destroyed in an HIV infection. Why do antibody levels fall in parallel with CD4 T cell counts?
3. Some promiscuous homosexual males with high risk of acquiring HIV remained uninfected for many years. It was discovered that they lacked a membrane molecule necessary for HIV infection of macrophages. In most infections via sexual intercourse, infection is due to transmission of HIV in macrophages. HIV enters macrophages by binding CD4 (macrophages have very low levels of CD4) + the chemokine receptor CCR5. Macrophage replication of HIV is very slow, but new virions can be produced and spread to macrophages. This HIV is called macrophage (M)-tropic. At some point in infection the gp120 on new viruses mutates to be able to bind CD4 + either CCR5 or CXCR4, a different chemokine receptor found on T cells. This "dual tropic" HIV can now spread to T cells. T cells allow faster replication of HIV and more rapid progression to symptomatic disease.
Compare and contrast the effects on the immune system of HIV destruction of macrophages and CD4 T cells.
4. We have known about HIV for two decades, but these is still no vaccine. Do you think we will ever have a vaccine to HIV? Why or why not?
5. Section 9-10 in Parham describes an inherited T cell deficiency that results from absence of CD40L production by T cells. Compare the consequences of this deficiency with AIDS. How are the symptoms similar and different? How is each disease treated and why?
Additional Information
Good site on HIV and Immunology http://www.biology.arizona.edu/immunology/tutorials/AIDS/HIVimmune.html