|MadSci Network: Immunology|
Hi Jake, In a sense you are right, the immunosupressants will do the same job as the HIV but I must say that the former is preferable than the latter. The most common immunosuppressants given to graft patients today are cyclosporin A and tacrolimus (FK506). These substances inhibit T lymphocyte activation mostly by interfering with the interleukin-2 (IL-2) pathway. IL-2 is a protein secreted by T cells themselves after they encounter an antigen to which they are specific. When the IL-2 binds to its receptor on the surface of the same T cell or of a neighboring T cell, it will cause the T cell to enter mitosis (cellular division). Since only activated T cell produce this protein, the site of inflammation will soon be filled with T cells specific for the antigen (which could come from a bacteria or a virus or anything else). Some of these T cells are able to direct the course of the immune response by acting on other cells (these are called CD4 T cells) while other T cells can directly kill other cells infected by a virus, a bacteria or a parasite (these are called CD8 T cells). By inhibiting the response of the T cells to the IL-2, the immunosuppressants inhibits the whole acquired immune response. HIV-1 works differently. It infects CD4 T cells and start to kill them by subverting their protein production machinery and producing copies of itself. This is very fast at the beginning of the infection (one to two weeks) and then slows down a lot because of the immune response. It does not stop completely though and the number of the CD4 T cells dwindle slowly but surely. Now imagine that the CD4 T cells are like the generals of a big army. The body will try to replenish the number of generals killed by the HIV but will ultimately fail because a too large number of them die each day. When the number of generals is too low, the army (immune system) does not know when and where to act. This causes immunosuppression. The CD8 cells are very active in a HIV-1 infection because they are in charge of killing HIV-1 infected cells until there are no more "generals" to tell them what to do. So then, the difference is that while the dose of the immunosuppressants can be adjusted, the HIV-1 is pretty hard to keep in check. Adjusting the dose of the immunusuppressant can keep your girlfriend from catching a cold while ensuring that she does not react against the graft or that the graft does not reacts against her (this phenomenon is called graft-vs-host disease). HIV-1 can be controlled by reverse transcriptase inhibitors and protease inhibitors (called HAART for highly active antiretroviral therapy) but it cannot be completely inhibited. This expand the life span of HIV-1 infected individuals but does not ensure that they will never develop AIDS. Moreover, the social effects are very different between someone infected with HIV-1 and someone who received a graft. People are prone to judge an HIV-1 infected person while they will view a graft patient as someone with a grave illness that just gets treated. Also, an HIV infected individual can transmit its disease to someone else while a graft patient has no such worries. As for the life span matter... I think that if no major infection or reject occurs and that your girlfriend respond well to the immunosuppressive agents, she could live a very long and healthy life (relatively speaking of course). One important thing to remember though is that no one really knows what is their "normal" life span. Hope this answered your question, Good luck to you and your girlfriend. Ciao! Mike
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