From: Billi Goldberg <bigoldberg@igc.apc.org>
Subject: Concise Explanation of CS and DTH
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6288
Organization: unspecified
Date: Tue, 6 Oct 92 20:00:48 PDT

                        HOW DNCB APPEARS TO WORK

This is the most concise, clear explanation of contact sensitivity and 
DTH and how it clears various infections.

The following is from Chapter 28 titled "Delayed-Type Hypersensitivity 
and the Induction of Activated, Cytotoxic Macrophages" in Fundamental 
Immunology (1989), second edition, published by Raven Press.

From 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."

From 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."