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 T4 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 T4 helper cells then proliferate forming T4 cells which then circulate and activate effector cells (primarily macrophages) to rid the sysem of the DNCB antigen. At the same time T4 memory cells are produced adding to the T4 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 T4 memory cells. 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 obligate intracellular type. The activation of these macrophages result in phagocytosis of the pathogens which are then presented by macrophages to T4 and T8 memory cells specific for the presented pathogen. The activated T cells 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 self and non-self parts of the antigen presenting cells (Class I and Class II MHC), 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 more self and non-self antigens thus activating even more T memory cells and increasing the Th1 response against the pathogens involved in AIDS. It is extremely important to remember that the antibody or Th2 or humoral responses 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) [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) [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."