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Biological Sciences
Malcolm Mac Kinnon

 Sustained immune activation during HIV infection can ultimately deplete the body’s supply of helper T cells and lead to the collapse of the host’s defences  An untreated HIV infection exhibits distinct phases, in which the loss of helper T cells happens at different rates and appears to be driven by different mechanisms  In the acute or initial, phase, HIV virions enter the host’s body and begin to replicate  HIV gains entry into a host cell by first latching onto the cell-surface protein CD4, then binding to a coreceptor  The coreceptor used by most of the HIV strains responsible for new infections is CCR5 o These viral strains can thus infect dendritic cells, macrophages, regulatory T cells, and especially memory and effector helper T cells  HIV replicates explosively, and the concentration of virions in the blood climbs steeply o At the same time, the concentrations of CD4 T cells plummet, largely because HIV kills them while replicating o Hardest hit are the memory helper T cells in the lymphoid tissues of the gut o Since the gut is both large and vulnerable to penetrations by pathogens, the loss of these T cells is a severe blow to the body’s defenses  The acute phase ends when viral replication slows and the concentration of virions in the blood drops o This slow down may be because that the virus simply runs short of host cells it can easily invade  In addition, the immune system mobilizes against the infection and killer T cells begin to target host cells infected with HIV o The host’s CD4 T cell counts recover somewhat  This slows HIV, but it has not been stopped  As the chronic phase begins, the immune system struggles to recover form its initial losses while continuing to fight the virus o Throughout the chronic phase, the immune system remains highly activated  Chronically activated state of the immune system may enhance some aspects of the host’s response to HIV  It also generates a steady supply of activated CD4 T cells in which HIV can replicate o And it burns through the host’s supply of naive and memory helper T cells by stimulating them to divide and differentiate into short-lived effector cells o Replacement of lost helper T cells ultimately depends on the production of new naive T cells by the thymus o Thymic output declines with age, however and is also impaired by HIV infection o HIV infection also damages the bone marrow and lymph nodes  as the battle goes on, immune system’s capacity to regenerate steadily erodes  viral load climbs again and the CD4 T cell counts fall  Chronic phase ends when the concentration of helper T cells in the blood drops below about 200 cells per cubic millimetre  With few helper T cells left, the immune system can no longer function o The patient develops AIDS o Syndrome is characterized by opportunistic infections with bacterial and fungal pathogens that rarely cause problems for people with robust immune systems  An HIV-infected individual that does not have the effect of anti-HIV drug therapy, if the individual has begun showing symptoms of AIDS, then the individual typically can expect to live two or three more years  AIDS begins when HIV infection has progressed to a point where the immune system does not function properly.  AZT, one of the first anti-AIDS drugs, turned out to be
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