4.2. Alternative treatments for HIV/AIDS: HOW DNCB WORKS
Description
This article is from the AIDS FAQ, by Dan Greening with numerous contributions by others.
4.2. Alternative treatments for HIV/AIDS: HOW DNCB WORKS
by Billi Goldberg
DNCB is applied weekly on the skin at various sites which initiates
contact sensitivity. The Langerhans cells in the skin at the
application site pick up the DNCB antigen, migrate from the skin,
change into veiled dendritic cells, continue their migration to the
nearest lymph node, change into interdigitating dendritic cells. Once
in the lymph nodes, they present the DNCB antigen to CD4 helper cells,
thus initiating a Th1 response or cell mediated immune response or
Type IV Delayed Type Hypersensitivity response (they can all be
considered the same thing).
The CD4 helper cells then proliferate forming more helper CD4 cells
which then circulate and activate effector cells (primarily
macrophages) to rid the sysem of the DNCB antigen. At the same time
CD4 memory cells are produced adding to the CD4 memory pool for the
DNCB antigen (hapten). Each time DNCB is applied, these memory cells
are activated thus initiating a systemic Th1 response to DNCB. The
longer DNCB is used, the response becomes faster, more potent, and
more effective because there are more circulating DNCB CD4 memory
cells to initiate the immune response.
The result of this specific systemic Th1 response to DNCB is the
non-specific activation of macrophages. Many of these macrophages are
infected with HIV and other intracellular pathogens that cause AIDS
but are unable to present these pathogen antigens due to
infection. The microbial pathogens of AIDS are of the facultative or
obligate intracellular type. The activation of these macrophages
result in phagocytosis of the pathogens which are then presented by
macrophages to CD4 and CD8 memory cells specific for the presented
pathogen. The activated helper and cytotoxic T lymphocytes initiate
specific systemic responses to destroy the presented pathogens. This
results in more activated macrophages, more pathogens presented, more
T memory cells activated, more infected cells destroyed, ad infinitum.
Since pathogens can be presented on both the Class I and Class II MHC
(major histocompatibility complex) of the antigen presenting cells,
cytotoxic T lymphocytes, natural killer cells, neutrophils, and killer
macrophages are also activated to accomplish the destruction. There is
also an excellent probability that dendritic cells (the most potent
antigen presenting cells in the immune system) are also activated in
the lymphoid tissues to present intracellular and extracellular
antigens thereby activating even more T lymphocyte memory, helper, and
effector cells thus increasing the Th1 response against the pathogens
involved in AIDS.
It is extremely important to remember that the antibody/Th2/humoral
response is not directly involved in fighting the infections of
AIDS. The denial of this fact is the primary reason that there has
been no progress in realistic treatments for AIDS. In point of fact,
there is research to show that activating the antibody or Th2 response
may suppress the Th1 response. This would allow the intracellular
pathogens to be uncontrolled since their control depends on the Th1 or
cell-mediated immune response. There is also research to show that
immune complexes (HIV + antibody) can be internalized through the
antibody receptor (Fc) of monocytes and macrophages thus spreading and
increasing HIV infection of these cells.
Delayed Type Hypersensitivity is an extremely effective and potent
immune modulator that forces priming and activation of macrophages
that are non-responsive due to infection. DNCB, then, acts like an
adjuvant or biological response modifier. These phenomena have been
researched in-depth and are considered a factual part of scientific
knowledge. On page 1292 of the recent edition of The Merck Manual is
the following: "Skin malignancies have regressed after induction of
delayed hypersensitivity to dinitrochlorobenzene (DNCB) and subsequent
direct application of DNCB to the tumor."
Below are the scientific explanations of what happens. This process
has been an integral part of the scientific literature for many
years. Meltzer and Nacy have explained it brilliantly. DNCB is not
new; it has been used for decades. But, since the cost of DNCB is
minimal and there is no profit to be made, it has been ignored.
The following is from Chapter 28 titled "Delayed-Type Hypersensitivity
and the Induction of Activated, Cytotoxic Macrophages" by Monte
S. Meltzer and Carol A. Nacy in Fundamental Immunology (1989), second
edition, published by Raven Press.
Page 775: "Contact sensitivity is a variant form of DTH in which
certain reactive chemicals (usually small molecular weight compounds
or metal ions that can diffuse into the epidermis) covalently bind to
skin proteins and create neoantigens. Such neoantigens prime or
sensitize the exposed animal to a second cutaneous application of the
reactive chemical (contactant). A portion of the neoantigen is host
derived. Thus an animal exposed to trinitrochlorobenzene (TNCB or
picryl chloride) solution epicutaneously responds to a repeated
cutaneous exposure with a vigorous DTH response. Intradermal injection
of TNCB covalently bound to an irrelevant protein such as albumin
fails to elicit this response. Neoantigens induced in the epidermis
are taken up by Langerhans cells. These highly efficient,
antigen-presenting dendritic cells migrate into the dermis, enter
lymphatics, and travel to the cortical region of the draining lymph
node where they present the antigen to CD4+ T cells. Application of
normally sensitizing chemicals to skin devoid of Langerhans cells
(skin treated with corticosteroids, UVB light, or cellophane adhesive
tape) does not induce contact sensitivity and may produce specific
immunologic tolerance to the contactant."
Pages 766-767: "Coincident with the development of DTH during
infection is a widespread activation of free and fixed mononuclear
phagocytes throughout the body. Tissue macrophages develop profound
alterations in morphology, cell proliferation, phagocytosis, and the
capacity to destroy intracellular and extracellular
microorganisms. Each of these changes is dependent on interactions
with sensitized lymphocytes. These systemic changes in the
antimicrobial activity of immunologically activated macrophages may
explain observations made as early as 1936 that animals responding to
reinfection with one microorganism (bacterium A) [ed. DNCB] acquire
the ability to resist nonspecifically infection with antigenically
unrelated pathogens (bacterium B, C, or D). Unlike the long-lived,
antigen specific, DTH response, this nonspecific element of acquired
resistance is short lived and can only be reexpressed by further
exposure to the original microbe (bacterium A) [ed. DNCB].
"Thus the DTH response to foreign antigens induces a series of immune
reactions whose ultimate purpose is the short-term accumulation of
nonspecifically cytotoxic, macrophage effector cells. Mononuclear
phagocytes rapidly and preferentially accumulate at sites of
infection. These inflammatory cells co-locate with antigen-reactive,
sensitized T cells and undergo dramatic changes in their functional
state. The activated macrophages that result are pleuripotent
cytotoxic effector cells which destroy viruses, bacteria, fungi,
single and multicellular parasites, allografts, and tumor cells. This
complex network of cell-mediated reactions is controlled by an even
more complex interaction of various cytokines, those released by the T
cell, the macrophage, and even the target cell. DTH reactions are not
self-destructive overreactions to foreign antigens, but rather tightly
controlled body defenses against tissue allografts, infection, and
neoplastic change."
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