From: bigoldberg@igc.apc.org (Billi Goldberg)
Newsgroups: sci.med.aids
Subject: TB, CMI and DTH
Date: 3 Sep 92 06:19:34 GMT
Organization: unspecified
Note: Copyright 1992, Dan R. Greening. Non-commercial reproduction allowed.
Archive-Number: 6058

Located an interesting article on tuberculosis. It should be included in the
references for the DNCB Fact Sheet that I just posted.

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Dannenberg Jr. AM. Delayed-type hypersensitivity and cell-mediated immunity in 
the pathogenesis of tuberculosis. Immunology Today 1991;12(7):228-233.

Review description of article:

"It is widely believed that cell-mediated immunity and the associated ability 
of macrophages to destroy or inhibit the bacillus are all that is required to 
control pulmonary tuberculosis. However, although cell-mediated immunity is a 
major defense against the tubercle bacillus, it is fully effective only in one 
of the four stages of the disease. Here, Arthur Dannenberg describes the 
entire pathogenesis of tuberculosis, with illustration from the rabbit model 
of M.B. Lurie. In addition, he documents that the delayed-type 
hypersensitivity reaction (producing tissue necrosis) greatly benefits the 
host by arresting the logarithmic growth of bacilli within immature 
macrophages."

Conclusions concerning CMI and DTH:

"CMI can be defined as a beneficial host response characterized by an expanded 
population of specific T cells, which, in the presence of microbial antigen, 
produce cytokines locally. These cytokines attract monocytes from the 
bloodstream into the lesion and activate them. DTH is immunologically the same 
process as CMI, involving T cells and their cytokines. However, pathologists 
can define DTH in tuberculosis as the immunological reaction that causes 
caseous necrosis, i.e. the death of local macrophages and nearby tissues.

"The relationship between CMI and DTH in the control of facultative 
intracellular microorganisms has been a subject of debate for most of this 
century. From the bacillary growth curves provided by Lurie and the 
accompanying histopathology, it is quite apparent that both CMI and DTH 
inhibit the multiplication of the tubercle bacillus equally well. However, CMI 
does so by activating macrophages to kill the bacilli they ingest; and DTH 
does so by killing bacilli-laden nonactivated macrophages and nearby tissues, 
thereby eliminating the intracellular environment, which is so favorable for 
bacillary growth.

"Thus, tuberculin-positive hosts with good CMI and tuberculin-positive hosts 
with poor CMI can arrest bacillary growth. But, such hosts with poor CMI do so 
by sacrificing much more of their own tissues. In time, the host with good CMI 
may recover, but the host with poor CMI will die from excessive tissue 
destruction. Local necrosis (produced by DTH) gives the host time to develop 
local macrophage activation (produced by CMI). However such necrosis can never 
take the place of CMI, because many bacilli survive and are ingested by new 
perifocal macrophages. In the cytoplasm of these macrophages, the bacilli 
again multiply - unless the macrophages have been activated by the 
cell-mediated immune process."
Newsgroups: sci.med.aids