MadSci Network: Immunology

Re: Are immunosupressants different than HIV?

Date: Sat Jan 26 00:11:36 2002
Posted By: Michel Ouellet, Grad student in Microbiology / Immunology
Area of science: Immunology
ID: 1010170262.Im

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) 

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 
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.



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