From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: Fauci and Lymph Nodes
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6747
Organization: unspecified
Date: Mon, 11 Jan 93 23:18:21 PST

Refer to my previous post on lymph nodes and follicular dendritic cells. 
This reinforces the concept that continuous immune reactions must be 
forced in the lymph nodes to destroy the HIV and HIV immune complexes 
that are building up. One way to trigger this immune response is with 
topical contact sensitizers utilizing delayed-type hypersensitivity type 
IV. This immune response utilizes antigen presenting cells (Langerhans-
dendritic) that migrate to the lymph nodes to initiate an APC--T4 helper 
cell activation. The result of this will be HIV presentation on class I 
MHC thus initiating specific cytotoxic T lymphocytes along with non-
specific activation of killer macrophages, ADCC, complement, killer 
lymphocytes, granulocytes, etc. that will destroy HIV infected cells, 
HIV particles, and HIV immune complexes in the lymph nodes

I have heard from two different sources connected with NIAID that they 
have done testing using AZT very early in HIV infection, and the AZT was 
totally worthless in clearing the virus from the nodes or stopping 
seroconversion or halting HIV pathogenesis.
***********************************************************************
The following is from the NIAID AIDS AGENDA, Fall 1992.

CLINICAL LATENCY TIME OF HIGH HIV REPLICATION

The symptomless stage of HIV infection, sometimes referred to as 
clinical latency, is actually a time of the continuous presence and 
high-level replication of HIV in the lymph nodes, according to recent 
studies carried out in NIAIDS's Laboratory of Immunoregulation.

Laboratory Chief and NIAID Director Anthony S. Fauci, M.D., presenting 
the findings in a state-of-the-science lecture at the VIII International 
Conference on AIDS in Amsterdam.

"We must rethink the concept of clinical latency," said Dr. Fauci. 
"Although little HIV can be detected in the blood during this period, 
there is sequestration of virus in the lymphoid tissue, active virus 
replication in the lymph nodes, and the induction of HIV expression. In 
addition, there are progressive functional abnormalities of CD4+ T cells 
as well as cytopathic effects on these cells."

Once it enters the body, HIV rapidly replicates and disseminates. Dr. 
Fauci and his group have demonstrated that during this period, called 
the acute or primary state of infection, large number of viral particles 
spread throughout the body, seeding themselves in various organs, 
particularly the lymph nodes. The lymph nodes act as a filtering system 
for the body, trapping invaders and presenting them to the squadrons of 
immune system cells that congregate there.

"Three to six weeks after exposure to the virus, up to 50 to 70 percent 
of HIV-infected person suffer flue-like symptoms related to this acute 
infection, such as fever, malaise, headaches and swollen lymph nodes," 
said Dr. Fauci.

A week to a month later, the patient's immune system fights back and 
CD4+ T cell levels may rebound to 80 or 90 percent of their original. 
Then, the patient generally goes into a symptomless stage lasting two to 
10 years, "during which time it is difficult to find the virus 
replicated in the peripheral blood mononuclear cells," said Dr. Fauci. 
"The patient often feels fine."

But, as Dr. Fauci and his colleagues have demonstrated, HIV is active 
within the lymphoid organs. Using techniques such as electron microscopy 
and polymerase chain reaction, the researchers have shown that early in 
the course of infection large amounts of the virus are trapped in the 
thread-like tentacles of follicular dendritic cells contained within the 
germinal centers of the lymph nodes.

In and around the germinal centers, CD4+ T cells become infected in 
increasingly large numbers. Many of these cells may be activated, 
allowing them to be more easily infected.

For years during an HIV infection, even though little virus may be 
present in the blood, significant numbers of HIV particles are 
accumulating in the germinal centers, both in infected cells and as free 
virus.

"At least 10 times more virus per any given number of cells may be 
present in the lymph nodes than is present in the bloodstream," Dr. 
Fauci said.

"Paradoxically, the filtering mechanism in the lymph nodes, which is so 
effective at trapping other invaders and initiating an immune response, 
may be an important reason why HIV is so effective at destroying the 
immune system, he added."

Ultimately, the NIAID researchers speculate, the lymph node is 
overwhelmed and the follicular dendritic cells break down. This leads to 
the release of large quantities of free virus into the bloodstream which 
heralds the later stages of HIV disease.

"During this burned-out stage, the follicular dendritic cells can no 
longer effectively filter and trap the virus," Dr. Fauci explains. "One 
see spillover of virus into the bloodstream, which manifests itself as 
accelerated viremia and ultimately advanced HIV disease."

A further understanding of the critical events early in HIV infection 
and the role of the lymphoid organs in the progression of HIV disease 
will have important implications for treatment. Toward this end, NIAID 
researchers are beginning a clinical trial to determine whether people 
would benefit from treatment with zidovudine (AZT) every soon after 
primary infection.

"This trial will help clarify gaps in our understanding of HIV 
immunopathogenesis, and elucidate the promise of therapeutic 
intervention early in the course of HIV infection," Dr. Fauci Said.
Newsgroups: sci.med.aids